Name: 1078-19-9|6-Methoxy-3,4-dihydronaphthalen-1(2H)-one|98%
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SKU: A156034
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1
[ 1730-48-9 ]
[ 1078-19-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	With oxygen In methanol; acetonitrile for 2h; Ambient temperature; Irradiation;
84.9%	With tetrabutylammonium perchlorate; water; sodium acetate In acetonitrile Electrochemical reaction; Green chemistry;
78%	With Bromotrichloromethane; Ir[2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine]<SUB>2</SUB>(4,4'-di-tert-butyl-2,2'-bipyridine)PF<SUB>6</SUB>; water; potassium carbonate In acetonitrile at 20℃; Irradiation; Inert atmosphere; regioselective reaction;

73%	With [bis(acetoxy)iodo]benzene; acetic acid; trifluoroacetic acid In tetrahydrofuran at 20℃; for 24h; chemoselective reaction;	General procedure for the benzylic C-H oxidation General procedure: To a solvent of (bisacetoxyliodo)benzene (DAIB) (4.75g, 14.75mmol) in dry THF (20-30mL) was added trifluoroacetic acid (1.12g, 9.83mmol) and acetic acid (0.29g, 4.92mmol). The mixture stirred for 30 min, after which the compound added for benzylic C-H oxidation (2.46mmol) and further reacted for 24h. The progress of the chemical reaction was monitored using thin-layer chromatography with precoated silica gel 60 (0.25mm thickness) plates. The reaction was quenched with 1mL of sat. NaHCO3 (aq), and the solvent removed in vacuo on a rotatory evaporator. The residue was extracted with ethyl acetate (30mL×2) and water (20mL). The combined organic extracts were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo.
72%	With Celite; pyridinium chlorochromate In benzene for 13h; Heating;
65%	With 2,3-dicyano-5,6-dichloro-p-benzoquinone In water; acetic acid for 0.5h; Heating;
61%	With tert.-butylhydroperoxide; chromium⁽⁰⁾ hexacarbonyl In acetonitrile for 23h; Heating;
60%	With 3,5-dimethylpyrazolium fluorochromate(VI) In dichloromethane for 10h; Heating;
	With chromium(VI) oxide; sulfuric acid
	With chromium(VI) oxide; acetic acid
	With chromium(VI) oxide; acetic acid; propionic acid
	durch anodische Oxidation;
	With chromium(VI) oxide; acetic acid
	With chromium(VI) oxide; acetic acid for 72h;
	With sulfuric acid; tetraethylammonium tosylate 1.) anodic oxidation, AcOH, MeOH 2.) RT, 3 h; Yield given. Multistep reaction;
	With chromium(VI) oxide; acetic acid

Reference： [1]Santamaria, Jean; Jroundi, Rachid [Tetrahedron Letters, 1991, vol. 32, # 34, p. 4291 - 4294]
[2]Ding, Mengning; Li, Xiaoshan; Sun, Yuxia; Xie, Jin; Xu, Wentao; Yang, Miao [Green Chemistry, 2020, vol. 22, # 21, p. 7543 - 7551]
[3]Pandey, Ganesh; Laha, Ramkrishna; Singh, Deepak [Journal of Organic Chemistry, 2016, vol. 81, # 16, p. 7161 - 7171]
[4]Lin, Chun-Yu; Yang, Ping-Shin; Chou, Pang-Yu; Ong, Chi Wi [Tetrahedron Letters, 2018, vol. 59, # 4, p. 365 - 367]
[5]Rathore, Rajendra; Saxena, Nishi; Chandrasekaran, S. [Synthetic Communications, 1986, vol. 16, # 12, p. 1493 - 1498]
[6]Lee, Hongmee; Harvey, Ronald G. [Journal of Organic Chemistry, 1988, vol. 53, # 19, p. 4587 - 4589]
[7]Pearson, Anthony J.; Han, Gi Rin [Journal of Organic Chemistry, 1985, vol. 50, # 15, p. 2791 - 2792]
[8]Bora, Upasana; Chaudhuri, Mihir K; Dey, Deepa; Kalita, Dipak; Kharmawphlang, Wancydora; Mandal, Gagan C [Tetrahedron, 2001, vol. 57, # 12, p. 2445 - 2448]
[9]Goertz,A. [Diss.<Tieraerztl.Hochsch.Berlin 1924> S.18]
[10]Schwenk; Papa [Journal of the American Chemical Society, 1945, vol. 67, p. 1432,1434] Miki [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1941, vol. 61, p. 272,278] Goertz,A. [Diss.<Tieraerztl.Hochsch.Berlin 1924> S.17] Hoch [Bulletin de la Societe Chimique de France, 1938, vol. <5> 5, p. 264,270][Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1938, vol. 207, p. 921] Burnop; Elliott; Linstead [Journal of the Chemical Society, 1940, p. 727,731]
[11]Thomas; Nathan [Journal of the American Chemical Society, 1948, vol. 70, p. 331,333]
[12]Juday [Journal of Organic Chemistry, 1957, vol. 22, p. 532,534]
[13]Emptoz,G. et al. [Chimica Therapeutica, 1969, vol. 4, p. 283 - 289]
[14]Jackman,L.M.; Thompson,D.T. [Journal of the Chemical Society, 1961, p. 4794 - 4808]
[15]Nishiguchi, Ikuzo; Hirashima, Tsuneaki [Journal of Organic Chemistry, 1985, vol. 50, # 4, p. 539 - 541]
[16]Current Patent Assignee: RIEDEL J D - DE397150, 1924, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 460][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 460]

2
[ 120-14-9 ]
[ 1078-19-9 ]
[ 149862-20-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium methylate In methanol at 20℃;	Synthesis of benzylidene tetralones 1-6; general procedure General procedure: A mixture of α-tetralone respective (1 mmol), an appropriate benzaldehyde (1 mmol) and sodium methoxide (catalytic) in methanol(8 mL) was stirred at room temperature over night. Water was addedand the resulting precipitate was collected by filtration, washed withwater and recrystallised from methanol.
90%	With toluene-4-sulfonic acid In ethanol for 24h; Reflux;
26%	With sodium hydroxide In water at 0 - 20℃; for 24h;

With methanol; sodium hydroxide

Reference： [1]Aparicio, Daniel A.; Lobo, Gricela M.; Sánchez, Jennifer L.; Monasterios, Melina C.; Acosta, María E.; De Lima, Lola; Llovera, Ligia J.; Ángel, Jorge E.; Charris, Jaime E. [Journal of Chemical Research, 2017, vol. 41, # 11, p. 668 - 672]
[2]Ranjbar, Sara; Akbari, Abdolhossein; Edraki, Najmeh; Khoshneviszadeh, Mahsima; Hemmatian, Hajar; Firuzi, Omidreza; Khoshneviszadeh, Mehdi [Letters in drug design and discovery, 2018, vol. 15, # 11, p. 1170 - 1179]
[3]Caleffi, Guilherme S.; Brum, Juliana De O. C.; Costa, Angela T.; Domingos, Jorge L. O.; Costa, Paulo R. R. [Journal of Organic Chemistry, 2021, vol. 86, # 6, p. 4849 - 4858]
[4]Peak et al. [Journal of the Chemical Society, 1936, p. 752,755]

3
[ 50-00-0 ]
[ 6091-44-7 ]
[ 1078-19-9 ]
[ 33279-02-6 ]

Reference： [1]Festschrift E. Barell <Basel 1946> S. 264, 294, 303,

4
[ 1826-67-1 ]
[ 1078-19-9 ]
[ 3125-36-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	In tetrahydrofuran at 40℃; for 1h;
92%	In tetrahydrofuran at 40℃; for 6h; Cooling with ice;
82%	In tetrahydrofuran at 40℃; for 48h; Inert atmosphere;	To an ice-cooled solution of vinyl magnesium bromide (90 mL, 90 mmol, 3.0 equiv, 1 M inTHF), a solution of ketone (5.3 g, 30 mmol, 1 equiv) in THF (40 mL) was added dropwise. Aftercomplete addition, the ice-bath was removed and the reaction was stirred at 40 °C for 2 days. Thereaction mixture was then cooled to 0 °C and a saturated aqueous solution of NH4Cl was carefullyadded, followed by EtOAc. The layers were separated and the aqueous layer was extracted twice withEtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated invacuo. The residue was purified by flash chromatography (SiO2, hexane/EtOAc), the title compound1s was isolated in 82% yield (5.0 g) as a pale yellow oil.

79%	Stage #1: vinyl magnesium bromide; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran for 2.5h; Stage #2: With water; ammonium chloride In tetrahydrofuran
68%	Stage #1: vinyl magnesium bromide; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran at 20℃; for 17h; Stage #2: With water In tetrahydrofuran Cooling with ice; Stage #3: With sodium tetrahydroborate In methanol for 0.5h;
68%	In tetrahydrofuran at 20℃; Reflux; Inert atmosphere;
	With tetrahydrofuran; diethyl ether
	In tetrahydrofuran for 1h; Heating;
	In tetrahydrofuran at 20℃; for 18h; Reflux;
	In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Reflux;
	In tetrahydrofuran at 0 - 20℃; Schlenk technique;	General Procedure for the Preparation of Allylic Alcohols General procedure: To a solution of 5-methoxy-1-tetralone (3.52 g, 20.0 mmol) in anhydrous THF (20 mL)in a Schlenk flask, was added CH2=CHMgBr in THF (1 mol·L-1, 50.0 mL, 50.0 mmol) at 0°C. The mixture was stirred for 3-4 h at rt. Saturated solution of NH4Cl (32 mL) was added dropwise at 0°C.The aqueous phase extracted with AcOEt, dried under anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (hexanes/AcOEt, 4:1), giving 2d (2.97 g, 14.6 mmol, 73%), as colorless oil.
	Stage #1: vinyl magnesium bromide; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran Stage #2: With ammonium chloride In water
	In tetrahydrofuran at 0℃;

Reference： [1]Sarabèr, Florence C. E.; Baranovsky, Alexander; Jansen, Ben J. M.; Posthumus, Maarten A.; De Groot, Aede [Tetrahedron, 2006, vol. 62, # 8, p. 1726 - 1742]
[2]Prevost, Sebastien; Dupre, Nathalie; Leutzsch, Markus; Wang, Qinggang; Wakchaure, Vijay; List, Benjamin [Angewandte Chemie - International Edition, 2014, vol. 53, # 33, p. 8770 - 8773][Angew. Chem., 2014, vol. 126, # 33, p. 8915 - 8918,4]
[3]Ye, Yang; Ma, Guobin; Yao, Ken; Gong, Hegui [Synlett, 2021, vol. 32, # 16, p. 1625 - 1628]
[4]Silva Jr., Luiz F.; Vasconcelos, Ramon S.; Nogueira, Mario A. [Organic Letters, 2008, vol. 10, # 5, p. 1017 - 1020]
[5]Weimar, Marko; Duerner, Gerd; Bats, Jan W.; Goebel, Michael W. [Journal of Organic Chemistry, 2010, vol. 75, # 8, p. 2718 - 2721]
[6]Location in patent: scheme or table Wefelscheid, Ulrike K.; Reissig, Hans-Ulrich [Tetrahedron Asymmetry, 2010, vol. 21, # 11-12, p. 1601 - 1610]
[7]Nasarow et al. [Doklady Akademii Nauk SSSR, 1957, vol. 112, p. 1067,1068][Doklady Chemistry, 112-117 <1957> 167, 169]
[8]Soorukram, Darunee; Knochel, Paul [Organic Letters, 2007, vol. 9, # 6, p. 1021 - 1023]
[9]Wefelscheid, Ulrike K.; Reissig, Hans-Ulrich [Advanced Synthesis and Catalysis, 2008, vol. 350, # 1, p. 65 - 69]
[10]Niu, Guang-Hao; Hou, Chieh-Shen; Chuang, Gary Jing; Wu, Chi-Phi; Liao, Chun-Chen [European Journal of Organic Chemistry, 2014, vol. 2014, # 18, p. 3794 - 3801]
[11]Silva, Siguara Bastos Lemos; Torre, Adriana Della; De Carvalho, Joo Ernesto; Ruiz, Ana Lcia Tasca Gois; Silva, Luiz F. [Molecules, 2015, vol. 20, # 1, p. 1475 - 1494]
[12]Fidarov, Alan F.; Vihma, Veera; Bogautdinov, Roman P.; Morozkina, Svetlana N.; Shavva, Alexander G.; Tikkanen, Matti J. [Journal of Steroid Biochemistry and Molecular Biology, 2015, vol. 154, p. 142 - 149]
[13]Gong, Quan; Wen, Jialin; Zhang, Xumu [Chemical Science, 2019, vol. 10, # 25, p. 6350 - 6353]

5
[ 1078-19-9 ]
[ 3470-50-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogen bromide; acetic acid; at 120℃; for 12h;	A 48% solution of hydrobromic acid (103 mL) is added to a solution of 6-methoxy-l-tetralone (10.0 g, 56.8 mmols) in glacial acetic acid (15 mL). The mixture is maintained at reflux at 120C and under stirring for 12 hours. After said time the solvent is evaporated at 1/p to obtain a crystalline solid essentially consisting of 3. 3: Yield: 98%. 'HNM (DMSO-d6): δ 1.98-3.20 (3m, 6H), 6.5-7.6 and 7.8-8.1 (2m, 3H).
93%	In hydrogen bromide;	6-Hydroxy-1-tetralone A solution of 6-methoxy-1-tetralone (6.0 g, 0.034 moles) in 48% aqueous hydrobromic acid (80 cm3) was refluxed for 2.5 h. The clear orange solution was then cooled to ice temp. and the resulting preicpitate was filtered off under suction, washed with cold water, and dried to afford the title compound as a pale orange solid (5.16 g, 93%), δH ›250 MHz: (CD3)2 SO! 1.99 (2H, m), 2.47 (2H, t), 2.82 (2H, t), 6.64 (1H, d), 6.71 (1H, dd), 7.73 (1H, d) and 10.31 (1H, broad s, OH).
92%	With hydrogen bromide; for 48h;Reflux;	A solution of 6-Methoxy-3,4-dihydro-2H-naphthalen-l-one (50.0 g, 284 mmol) in 48 % HBr (500 mL) was refluxed for 48 h, and the mixture was then cooled and poured into water (1 L). The solid was filtered and dried to give 6-Hydroxy-3,4-dihydro-2H- naphthalen-l-one (42.3 g, 92.0 %) as a white solid. MS ESI calc'd for Ci0H10O2 [M + H] + 163, found 163.

89.5%	With hydrogen bromide; sodium carbonate; acetic acid; In water;	a 6-hydroxy-1-tetralone A mixture of 50 g of 6-methoxy-1-tetralone, 200 ml of acetic acid and 400 ml of hydrobromic acid (47% HBr) was heated under reflux for 24 hours. After cooling, the reaction mixture was poured into 3 liters of water, solid matter was filtered out, and the resulting filtrate was extracted three times with ethyl acetate. The extracts were washed with an aqueous solution of sodium carbonate, dried over sodium sulfate and evaporated. The resulting residue together with the filtered solid matter was recrystallized from ethyl acetate to yield 40.75 g (89.5% of the theoretical yield) of 6-hydroxy-1-tetralone in the form of reddish-brown crystals melting at 153-155 C. 1 H-NMR (CDCl3): 2.07-2.15 (m, 2H, CH2); 2.62-2.66 (t, 2H, CH2); 2.89-2.93 (t, 2H, CH2);
89%	With aluminum (III) chloride; In toluene; for 1h;Reflux;	The title compound was prepared by from commercially available 6-methoxy-1-tetralone (8) according to the method in literature.1 Commercially available 6-methoxy-1-tetralone (10 g, 56.7 mmol) was added to a suspension of anhydrous aluminum trichloride (18.9 g, 142 mmol) in toluene (60 mL) at room temperature. The mixture was refluxed for 1 h, cooled and cautiously quenched with water (130 mL) and extracted with 150 mL (×3) of ethyl acetate. The organic layer was washed with water (50 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was recrystallised from ethyl acetate to yield 6-hydroxy-1-tetralone (89% yield).
89%	With aluminum (III) chloride; In toluene; for 1h;Reflux;	The title compound was prepared by from commercially available 6-methoxy-1-tetralone (8) according to the method in literature. Commercially available 6-methoxy-1-tetralone (10 g, 56.7 mmol) was added to a suspension of anhydrous aluminum trichloride (18.9 g, 142 mmol) in toluene (60 mL) at room temperature. The mixture was refluxed for 1 h, cooled and cautiously quenched with water (130 mL) and extracted with 150 mL (×3) of ethyl acetate. The organic layer was washed with water (50 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was recrystallised from ethyl acetate to yield 6-hydroxy-1-tetralone (89% yield).
86.4%	In hydrogen bromide;	EXAMPLE 1 STR10 6-Hydroxy-1-tetralone 2 mols cf 6-methoxy-1-tetralone are heated at 125 C. in 2 l of 48% strength aqueous hydrobromic acid for 3 hours. On cooling, the product precipitates and is filtered off with suction and dried. If necessary, it can be recrystallized from water. Yield 86.4% of theory Melting point: 155 -57 C.
86%	With hydrogen bromide; In water;Reflux;	10640] Aqueous H13r (100 mL) was added to 6-methoxy-1 -tetralone (10.0 g, 56.8 mmol), and the reaction mixture was refluxed for overnight. The reaction mixture was then broughtto room temperature and extracted with ethyl acetate (2x100mL). The organic layer was dried over sodium sulphate, fil- tered and removed under reduced pressure. The crude product was purified using flash chromatography using 40% ethylacetate in hexanes to afford title compound (8.0 g, 86%) as solid. ‘H NMR (400 MHz, CDC13): ö 7.99 (d, J8.0 Hz, 1H), 6.78 (d, J8.4 Hz, 1H), 6.69 (s, 1H), 6.23 (bs, 1H), 2.9 (t, J6.0 Hz, 2H), 2.62 (t, J6.0 Hz, 2H), 2.11 (m, 2H); ESI-MS mIz163 (M+H).
86%	With hydrogen bromide; In water; at 100℃; for 24h;	The reaction mixture of 6-methoxy-3,4-dihydronaphthalen-1 (2H)-one (17.6 g, 100 mmol/L) and 40% hydrobromicacid aqueous solution (100 mL) was stirred at 100 C for24 h and then cooled to room temperature. The reactionsolution was added to ice water to stir a large amount ofsolid to precipitate. The solid was filtered and washed with5% carbonic acid aqueous solution of sodium hydride, and then washed with deionized water to neutral and dried. Thecrude product was purified by silica gel column eluting withethyl acetate: n-hexane = 1:5.
83%	With aluminum (III) chloride; In dichloromethane; at 80℃; for 42h;	To a solution of 6-methoxytetralone (1.0 g, 5.7 mmol) in CH2Cl2 (10 mL), AlCl3 (3.8 g, 28.4 mmol) was carefully added. The reaction was warmed up to 80 C and stirred during 42 h. The reaction mixture was poured into ice-water (20 mL), and extracted with AcOEt (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtrated and evaporated under reduced pressure. The crude was purified by flash chromatography on silica gel (1:4 AcOEt:hexane), to afford the desired product (0.76 g, 83%) as a cream-coloured solid. Mp: 154-157 C. IR: 3025, 2936, 1644, 1567, 1479. 1HNMR (CDCl3) δ: 7.98 (d, 1H, J = 8.5), 7.93 (s, 1H), 6.81 (dd, 1H, J = 8.5, 2.5), 6.72 (d, 1H, J = 2.3), 2.90 (t, 2H, J = 6.2), 2.63 (t, 2H, J = 6.4), 2.10 (q, 2H, J = 6.4). Spectroscopic data were coincident with literature.
83%	With hydrogen bromide; In water; acetic acid; ethyl acetate;	EXAMPLE 22 6-Isopropoxy-1-tetralone Commercial 6-methoxy-1-tetralone (50 g., 0.284 mole) was dissolved in 200 ml. glacial acetic acid and 300 ml. of 48% hydrobromic acid was added. The resulting solution was refluxed for 24 hours, then allowed to stir and cool to room temperature overnight. The reaction mixture was poured into 1 liter of cool water, the resulting slurry extracted with 500 ml. ethyl acetate and the aqueous layer extracted again with 2 * 200 ml. ethyl acetate. The combined organic layers were washed with 2 * 200 ml. water then carefully washed with saturated NaHCO2 solution (foaming) until acidic products are neutralized. The organic extracts were dried over saturated aqueous NaCl solution then with solid MgSO4 and carbon treated. After filtration, the extracts were evaporated to dryness to afford 38.1 g. of 6-hydroxyl-1-tetralone, m.p. 151-152.5 C. (83% yield).
79%	With 1-N-ferrocenylmethyl benzimidazole tagged polymer; In N,N-dimethyl-formamide;Reflux;	General procedure: A mixture of aryl methyl ether (1 mmol) and [FemMerBenz]Al2Cl7 (200 mg, 0.96 mol %) in DMF (5 mL) was refluxed in an oil bath. After completion of the reaction as monitored by the TLC, the reaction mixture was cooled and filtered. The filtrate was poured into water (20 mL) and extracted with ethyl acetate (3 20 mL). The combined organic layers were dried over Na2SO4. Evaporation of the solvent followed by column chromatography over silica gel using ethyl acetate/ petroleum ether (1:4 v/v) afforded pure O-demethylated product, which was characterized by spectral methods.
74%	In hydrogen bromide;	2. 6-Hydroxy-2,3,4-trihydronaphthalen-1-one 6-Methoxytetralone (167 g, 0.95 mol, Aldrich Chem. Co.) is dissolved in 48% hydrobromic acid and heated to reflux for 5 hours. After stirring for 18 hours at 25 C., an orange solid precipitates. The solid is filtered, partitioned between water and ethyl ether, and filtered off. The solid is exhaustively extracted into ethyl ether which is evaporated to a pink solid (114 g, 74% yield). MS: APCI: M+1, 163.1 (M: 162.2).
38.8%		Example 18; Preparation of l-oxo-l,2,3,4-tetrahydro-6-hydroxynaphthalene by demethylation of l-oxo-l,2,3,4-tetrahydro-6-methoxynaphthalene of the formula (IX) CH3(IX)To a mixture of 5.67 g (42.5 mmol) of aluminium chloride and 2.28 g (30 mmol) of thiourea 1.76 g (10 mmol) of l-oxo-l,2,3,4-tetrahydro-6-methoxynaphthalene is added. The reaction mixture is heated to 90 C, maintained at this temperature for 3 hours, then cooled to room temperature and 20 ml of 1,2-dichloroethane is added. The mixture is poured to 20 ml of 5 wt % hydrochloric acid and is stirred at 50 C for 1 hour.The mixture is cooled to room temperature, the phases are separated and the aqueous layer is extracted with 20 ml of 1,2-dichloroethane. The combined dichloroethane phases are washed with 3 x 10 ml of 5 wt % aqueous sodium hydroxide solution. The alkaline phases are combined, acidified with 18 wt % hydrochloric acid solution and extracted with 3 x 10 ml of dichloromethane. The combined dichloromethane phases are washed with water, dried over sodium sulfate and evaporated yielding 0.63 g (38.8 %) of l-oxo-l,2,3,4-tetrahydro-6- hydroxynaphthalene. EPO <DP n="23"/>
	With hydrogen bromide; In water; at 0 - 120℃;	A suspension of 6-methoxy-1-tetralone (99 g) in 48% hydrobromic acid (800 ml) was stirred overnight at 120C. The reaction mixture was poured into ice water, the resulting solid was sequentially washed with water and hexane-diethyl ether system. To a solution of the resulting 6-hydroxy-3,4-dihydro-2H-naphthalen-1-one (76 g) in. N,N-dimethylformamide (400 ml) were sequentially added potassium carbonate (76 g) and benzyl bromide (59 ml), and the solution was stirred for 4 hours at room temperature. The reaction mixture was poured into water, the resulting solid was sequentially washed with water and hexane-diethyl ether system to provide the title compound (110 g).1H-NMR (400MHz, CDCl3); δ (ppm): 2.12 (pent, 2H), 2.61 (t, 2H), 2.92 (t, 2H), 5.12 (s, 2H), 6.79 (d, 1H), 6.90 (dd, 1H), 7.32-7.45 (m, 5H), 8.01 (d, 1H).
	In hydrogen bromide;	(i) A solution of 6-methoxy-1-tetralone (5.0 g) in 48% hydrobromic acid (62 ml) was refluxed for 8 hours. The mixture was cooled, filtered and washed with water (50 ml) to give 6-hydroxy-1-tetralone (3.91 g): NMR δ (d6 DMSO) 1.9-2.05(m,2H), 2.4-2.55(m,2H), 2.8-2.9(m,2H), 6.65(d,1H), 6.7(dd,1H), 7.75(d,1H),; m/e 163(M+H)+.
22.3 g tan powder, (81%)	AlCl3; In benzene;	EXAMPLE 87 6-Hydroxy-α-tetralone A mixture of 6-methoxy-α-tetralone (30 g, 0.17 mole), AlCl3 (45 g, 0.34 mole), and benzene (300 mL) was stirred at reflux for overnight. After cooling to room temperature, the reaction mixture was poured onto ice. The solid was filtered, washed with water, dried (in vacuo) to yield 22.3 g tan powder, (81%); M+ 162.
	With pyridine hydrochloride; In water;	(1) Synthesis of 6-hydroxy-1-tetralone A mixture of 25.0 g of 6-methoxy-1-tetralone and 80.0 g of pyridine hydrochloride was stirred at 200C for 5 hours and then allowed to cool to room temperature. Water was added thereto. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by the use of a column to obtain 17.6 g of an intended product. 1H NMR (CDCl3, δ) 2.06-2.19 (2H, m), 2.63 (2H, t), 2.91 (2H, t), 6.71-6.80 (3H, m), 7.98 (1H, d).
		A. 6-Hydroxy-3,4-dihydro-2H-naphthalen-1-one This compound was prepared from 6-methoxy-tetralone, by the method described in Example 10A. 1 H NMR (250 MHz, CDCl3): d 8.0 (d, 1 H), 6.77 (dd, 1 H), 6.70 (d, 1 H), 2.91 (t, 1 H), 2.65 (t, 1 H), 2.10 (m, 1 H).

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[25]Patent: US6359138,2002,B1 .Location in patent: Page column 34
[26]Tetrahedron Letters,2012,vol. 53,p. 6361 - 6366,6
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[28]Patent: US2004/44057,2004,A1
[29]Tetrahedron,1980,vol. 36,p. 1327 - 1330
[30]Patent: WO2006/61666,2006,A2 .Location in patent: Page/Page column 21
[31]Diss.<Univ.Berlin 1933> S.40,
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6
[ 1078-19-9 ]
[ 22604-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen sulfide;	a. 6-Methoxy-1-naphthol An intimate mixture of 81.5 g. (0.462 mole) of 6-methoxy-1-tetralone and 14.5 g. (0.465 mole) of sulfur is heated at 240°-250° for 6 hours and distilled to give 39.8 g. of oil, b.p. 158°-164° (0.3 - 0.5 mm.).

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 1345 - 1355
[2]Tetrahedron,1995,vol. 51,p. 11531 - 11546
[3]Chemische Berichte,1959,vol. 92,p. 1643,1652
[4]Chimica Therapeutica,1969,vol. 4,p. 283 - 289
[5]Canadian Journal of Chemistry,1968,vol. 46,p. 3625 - 3629
[6]Tetrahedron,1963,vol. 19,p. 1919 - 1937
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[8]Liebigs Annalen der Chemie,1980,p. 533 - 541
[9]Canadian Journal of Chemistry,1968,vol. 46,p. 3625 - 3629
[10]Patent: US3935267,1976,A
[11]Tetrahedron Asymmetry,2009,vol. 20,p. 467 - 472

7
[ 1078-19-9 ]
[ 54951-36-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydroxylamine hydrochloride
96%	With hydroxylamine hydrochloride; sodium acetate In methanol at 70℃; for 1.5h;
95%	With hydroxylamine hydrochloride; sodium acetate In methanol; water at 60℃; for 12h;

88%	With pyridine; hydroxylamine hydrochloride at 20℃; for 3h;	4.1.3. General produce for the preparation of 2,3,4,5-tetrahydro-1Hbenzo[b]azepine by reductive ring expansion General procedure: Hydroxylamine hydrochloride (2 equiv) was added to a stirredsolution of 3,4-dihydronaphthalen-1(2H)-one in pyridine (1 equiv).After the mixture was stirred for 3 h at room temperature, pyridinewas removed under reduced pressure. Then the products wereisolated following recrystallizations from aqueous ethanol. Moreover, the mixture could be extracted by EtOAc and purified bycolumn chromatography (PE/EA 5/1) to yield corresponding 3,4-dihydronaphthalen-1(2H)-one oxime.DIBALH (1Min n-hexane, 6 equiv)was added to a stirred solutionof 3,4-dihydronaphthalen-1(2H)-one oxime inCH2Cl2 drop by drop at0 C. Then the mixture was transferred to room temperature andstirred for another 2 h. The reaction was quenched carefully byaddition of NaF (12 equiv) and water at 0 C. The aluminum saltprecipitated out as colloid. Then the mixture was stirred at roomtemperature for another 2 h, and aluminumsaltwas filtered as sandlikesolid. The filtrate was dried over Na2SO4 and concentrated invacuo. The crude product was purified by column chromatography(Al2O3, PE/EA 5:1) to give 2,3,4,5-tetrahydro-1H-benzo[b]azepine.Then the designed compounds were obtained as methodsabove.
79%	With hydroxylamine hydrochloride In ethanol for 1h; Reflux;
	With potassium carbonate; ammonium chloride In methanol; water for 2h; Heating; Yield given;
	With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 20℃; for 4h; Heating / reflux;	4.A Dissolve 100 g (0.57 mol) of 6-methoxy-1-tetralone in 2.5 litres of a mixture of ethanol/water: 80/20. There are then added, at ambient temperature, 85 g (1.04 mol) of sodium acetate and 43 g (0.62 mol) of hydroxylamine hydrochloride. Heat the suspension at reflux for 4 hours. Dilute the mixture with 5 litres of water and extract with ethyl ether, wash with water, dry over magnesium sulphate and filter. After evaporating off the solvent, 99 g of a beige solid are obtained.
	With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 20℃; for 4h; Heating / reflux;	4.A Step A : 6-Methoxy-3,4-dihydro-1(2H)-naphthalenone oxime [0062] Dissolve 100 g (0.57 mol) of 6-methoxy-1-tetralone in 2.5 litres of a mixture of ethanol/water: 80/20. There are then added, at ambient temperature, 85 g (1.04 mol) of sodium acetate and 43 g (0.62 mol) of hydroxylamine hydrochloride. Heat the suspension at reflux for 4 hours. Dilute the mixture with 5 litres of water and extract with ethyl ether, wash with water, dry over magnesium sulphate and filter. After evaporating off the solvent, 99 g of a beige solid are obtained.
	With hydrogenchloride; n-Butyl nitrite; potassium In ethanol; water; <i>tert</i>-butyl alcohol	1 6-methoxy-1-tetralone oxime 6-methoxy-1-tetralone oxime In 60 ml of refluxing t-butanol was dissolved 3.84 g (0.0985 mole) of potassium. Ether (150 ml) was added followed by 15.87 g (0.09 mole) of 6-methoxy-1-tetralone. Butyl nitrite (11.1 g, 0.0932 mole) was added dropwise with stirring over a period of 30 minutes. The insoluble salts were filtered and washed with ether. They were slurried with 180 ml of water and then 15 ml of Concentrated HCl was added. The initially formed oil solidified. The solid was filtered and washed with water. Recrystallization of the still damp product from 250 ml of ethanol gave 8.86 g. Concentration of the filtrate to 1/3 volume gave 2.06 g additional material. Total yield 10.92 g (59%). A second recrystallization gave an analytical sample, mp 168°-171° dec.
	With hydroxylamine hydrochloride; sodium acetate In methanol at 60℃; for 2h;
	With hydroxylamine hydrochloride; potassium acetate In ethanol at 100℃; for 1h;	1 [Synthesis Example1]; 6-Methoxy-1-tetralone (10 g), hydroxylamine hydrochloride (6 g) and potassium acetate (10 g) were added to ethanol (100 mL), and the resultant solution was stirred for 1 hour under heating at 100°C. After consumption of the starting materials had been confirmed through TLC, the mixture was poured into water (200 mL) for precipitation. The precipitated crystals were recovered through filtration and then recrystallized from acetonitrile (80 mL), to thereby yield 10.0 g of an oxime compound raw material. The thus-obtained oxime compound raw material was measured for 1H-NMR spectrum (300 MHz, CDCl3), which was found to be δ: 1.8 (q, 2H), 2.6-2.7 (m, 4H), 3.8 (s, 3H), 6.7-6.8 (m, 2H), 7.8 (d, 1H). This oxime compound raw material (2.0 g) and pyridine (10 g) were dissolved in tetrahydrofuran (10 mL). The resultant solution was cooled to 0°C and then added dropwise to methyl chloroformate (1.5 g) at the same temperature. The mixture was increased to room temperature, followed by stirring for 2 hours. After consumption of the starting materials has been confirmed through TLC, the mixture was poured into water (60 mL). The precipitated crystals were recovered through filtration and then purified through silica gel chromatography, to thereby yield 1.5 g of the oxime compound having Structural Formula (5). The 1H-NMR spectrum (300 MHz, CDCl3) of the oxime compound was found to be δ: 1.9 (q, 2H), 2.7 (t, 2H), 2.9 (t, 2H), 3.8 (s, 3H), 3.9 (s, 3H), 6.6 (s, 1H), 6.8 (d, 1H), 8.1 (s, 1H).
	With hydroxylamine hydrochloride; sodium acetate In methanol at 80℃; for 2h;	2 INTERMEDIATE 26-Methoxy-3 ,4-dihydronaphthalen- 1 (2H)-one oxime [00189] A solution of 6-methoxy-3,4-dihydronaphthalen-l(2H)-one (5 g, 28.4 mmol), hydroxylamine hydrochloride (2.366 g, 34.0 mmol) and sodium acetate (2.79 g, 34.0 mmol) in anhydrous methanol (20 mL) was heated at 80 °C (oil bath temp.) for 2 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Next, 75 mL of water was added to the resulting solid and the contents were triturated and filtered. The solid was washed with addition water (2 x 50 mL), toluene (50 mL) and then dried for 80 h to yield 4.2 g of the oxime as a white solid. A second crop of additional product (1. lg of pink solid) was obtained from the mother liquor. XH NMR (400 MHz, CDC13) δ ppm 1.83-1.91 (m, 2 H) 2.70-2.83 (m, 4 H) 3.81 (s, 3H) 6.66 (d, J=2.76 Hz, 1 H) 6.77 (dd, J=8.78, 2.76 Hz, 1 H) 7.83 (d, J=8.78 Hz, 1 H) 8.32 (br. s., 1 H).
	With hydroxylamine hydrochloride; sodium acetate In ethanol at 65℃; for 2h;
	With hydroxylamine hydrochloride; sodium acetate In ethanol at 20℃; for 6h;	96 First step, hydroxyamine hydrochloride (2.60 g) and NaOAc (3.40 g) were added to a solution of 6-methoxy-1, 2, 3, 4-tetrahydro-1-tetralone (3.52 g) in EtOH (80 ml). The reaction mixture was stirred at room temperature for 6 h. EtOH was removed under reduced pressure. H2O (40 ml) was added to the residue, and the resulting solution was extracted with EtOAc (3 × 40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield 6-methoxy-1, 2, 3, 4-tetrahydro-1-tetralone oxime (3.74 g) as a pale yellowish solid. Second step, 6-methoxy-1, 2, 3, 4-tetrahydro-1-tetralone oxime (1.87 g) and concentrated HCl (4 ml) in EtOH (50 ml) was subjected to hydrogenation at atmospheric pressure in the presence of 10% Pd/C (150 mg). The reaction solution was filtered and the filtrate was concentrated. The residue was suspended in EtOAc, and the suspension was filtered to yield (+/-)-6-methoxy-1,2,3,4-tetrahydro-naphthalene-1-ylamine hydrochloride (2.13 g) as a white solid. Third step, a mixture of (+/-)-6-methoxy-1, 2, 3, 4-tetrahydro-naphthalene-1 -ylamine (298 mg, the hydrochloride), 6-chloropurine riboside (200 mg) and triethylamine (3 ml) in PrOH (60ml) was heated to 70°C and reacted for 8 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (20 : 1) to yield N6-[(+/-)-(6-methoxy-1,2,3,4-tetrahydro-naphthalene-1-yl)]-adenosine(240 mg) as a white solid: positive ESIMS m/z 428 [M + H]+ and 450[M + Na]+; negative ESIMS m/z 462 [M+Cl]-; 1H NMR (300 MHz, DMSO-d6): the adenosine moiety δ 8.35 (1H, s, H-2), 8.24 (1H, brs, H-8), 7.96 (1H, d, J = 8.7 Hz, -NH), 5.89 (1H, d, J = 6.3 Hz, H-1), 5.44 (1H, d, J= 6.9 Hz, -OH), 5.40 (1H, m, -OH), 5.18 (1H, d, J= 4.8 Hz, -OH), 4.62 (1H, m, H-2'), 4.14 (1H, m, H-3'), 3.96 (1H, m, H-4'), 3.66 (1H, m, H-5'a), 3.55 (1H, m, H-5'b); the (+/-)-(6-methoxy-1,2,3,4-tetrahydro-naphthalene -1-yl) moiety δ 7.04 (1H, d, J = 9.0Hz, H-8"), 6.65 (2H, m, H-5", H-7"), 5.58 (1H, m, H-1), 3.69 (3H, m, -OCH3), 2.73 (2H, m, H-4"), 1.96 (2H, m, H-3"), 1.94, 1.72 (1H, m, each, H-2"); 13C NMR (75 MHz, DMSO-d6): the adenosine moiety δ 154.4 (s, C-6), 152.6 (d, C-2), 148.6 (s, C-4), 139.9 (d, C-8), 119.6 (s, C-5), 88.2 (d, C-1), 86.1 (d, C-4'), 73.6 (d, C-2'), 70.9 (d, C-3'), 61.8 (t, C-5'); the (+/-)-(6-methoxy-1,2,3,4-tetrahydro-naphthalene-1-yl) moiety δ 158.0 (s, C-6"), 138.7 (s, C-4"a), 130.1 (d, C-8"), 129.1 (d, C-8"a), 113.1 (d, C-5"), 112.4 (d, C-7"), 56.1 (q, -OCH3), 47.2 (d, C-1), 29.9 (t, C-2"), 29.4 (t, C-3"), 20.6 (t, C-4")o
3.74 g	With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 6h;	96 First step, hydroxyamine hydrochloride (2.60 g) and NaOAc (3.40 g) were added to a solution of 6-methoxy-1,2,3,4-tetrahydro-1-tetralone (3.52 g) in EtOH (80 ml). The reaction mixture was stirred at room temperature for 6 h. EtOH was removed under reduced pressure. H2O (40 ml) was added to the residue, and the resulting solution was extracted with EtOAc (3*40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield 6-methoxy-1,2,3,4-tetrahydro-1-tetralone oxime (3.74 g) as a pale yellowish solid.
	With hydroxylamine hydrochloride; sodium acetate In methanol for 4h; Reflux;
	With hydroxylamine hydrochloride; sodium acetate In methanol at 20℃; for 12h;
3.74 g	With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 6h;	96.1 First step weigh precisely 6-methoxy-1,2,3,4-tetralin-1-ketone (3.52 g), hydroxylamine hydrochloride (2.60 g) and anhydrous sodium acetate (3.40 g), add ethanol ), Stir at 60 ° C. for 6 hours, recover the solvent with the reaction solution, add 40 mL of water, mix well, dissolve, extract with ethyl acetate 40 ml, extract a total of 3 times , The solvent is recovered with a phase of ethyl acetate to give 6-methoxy-1,2,3,4-tetralin-1-oxime (3.74 g) as a pale yellow solid.
	With hydroxylamine hydrochloride; sodium acetate In methanol for 2h; Reflux; Inert atmosphere;

Reference： [1]Tang, Wenjun; Capacci, Andrew; Sarvestani, Max; Wei, Xudong; Yee, Nathan K.; Senanayake, Chris H. [Journal of Organic Chemistry, 2009, vol. 74, # 24, p. 9528 - 9530]
[2]Shrestha, Pradeep; Dissanayake, Komadhie C.; Gehrmann, Elizabeth J.; Wijesooriya, Chamari S.; Mukhopadhyay, Atreyee; Smith, Emily A.; Winter, Arthur H. [Journal of the American Chemical Society, 2020, vol. 142, # 36, p. 15505 - 15512]
[3]Angeles-Dunham, Veronica V.; Nickerson, David M.; Ray, Devin M.; Mattson, Anita E. [Angewandte Chemie - International Edition, 2014, vol. 53, # 52, p. 14538 - 14541][Angew. Chem., 2014, vol. 126, # 52, p. 14766 - 14769,4]
[4]Guo, Zheng; Zhang, Zixue; Zhang, Yi; Wang, Guan; Huang, Ziyi; Zhang, Qinwei; Li, Jianqi [European Journal of Medicinal Chemistry, 2021, vol. 218]
[5]Location in patent: scheme or table Chanda, Debabrata; Saikia, Dharmendra; Kumar; Thakur, Jay Prakash; Agarwal, Jyoti; Chanotiya; Shanker, Karuna; Negi, Arvind S. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 13, p. 3966 - 3969]
[6]Miki [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1941, vol. 61, p. 272,278] Schroeter et al. [Chemische Berichte, 1930, vol. 63, p. 1308,1325] Goertz,A. [Diss.<Tieraerztl.Hochsch.Berlin 1924> S.18]
[7]Perrone; Berardi; Tortorella [Farmaco, Edizione Scientifica, 1984, vol. 39, # 3, p. 255 - 264]
[8]Current Patent Assignee: SERVIER MONDE - US2005/59675, 2005, A1 Location in patent: Page/Page column 4
[9]Current Patent Assignee: SERVIER MONDE - US2003/199555, 2003, A1 Location in patent: Page/Page column 3
[10]Current Patent Assignee: The United States of America as represented by the Secretary of the Navy - US753, 1990, H1
[11]Zhou, Hai; Chung, Wan-Jun; Xu, Yun-He; Loh, Teck-Peng [Chemical Communications, 2009, # 23, p. 3472 - 3474]
[12]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - EP2116527, 2009, A1 Location in patent: Page/Page column 61
[13]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2011/59784, 2011, A1 Location in patent: Page/Page column 78-79
[14]Phipps, Robert J.; Hiramatsu, Kenichi; Toste, F. Dean [Journal of the American Chemical Society, 2012, vol. 134, # 20, p. 8376 - 8379]
[15]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - EP2511283, 2012, A1 Location in patent: Page/Page column 91
[16]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - US2013/45942, 2013, A1 Location in patent: Paragraph 0382
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[19]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - JP2015/172077, 2015, A Location in patent: Paragraph 0188
[20]Current Patent Assignee: RIEDEL J D - DE397150, 1924, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 460][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 460]
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8
[ 105-58-8 ]
[ 1078-19-9 ]
[ 16425-80-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: Diethyl carbonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran; mineral oil at 0 - 80℃; for 12h; Inert atmosphere; Schlenk technique;
91.8%	With sodium hydride In tetrahydrofuran for 48h; Heating / reflux;	2.a NaH (3.4 g, 60% in mineral oil, 83.3 mmol) was washed with hexanes (3×70 mL) and THF (1×30 mL) in an oven dried 3 neck round-bottomed flask. Diethyl carbonate (5.5 mL, 45.4 mmol) was added to the NaH/THF suspension in anhydrous THF (20 mL) and the slurry was heated at reflux under N2. 6-Methoxy-1-tetralone (4 g, 22.7 mmol) in THF (40 mL) was added dropwise via an addition funnel to the suspension at reflux. The reaction mixture was then heated at reflux for 2 days. The solution was cooled to room temperature and glacial AcOH (3.6 mL) was added in a dropwise manner. Et2O (150 mL) was then added and the organic layer was washed with saturated NaCl solution (5×25 mL), dried (MgSO4), and concentrated under reduced pressure to provide a crude brown oil (6.0 g). The oil was subjected to medium pressure chromatography on silica (CHCl3) to provide a dark oil which solidified upon standing (5.17 g, 91.8% yield). The solid was recrystallized from EtOAc/hexane to provide a white solid. mp 58-60° C. 1H-NMR (300 MHz, CDCl3) δ 1.27-1.36 (t, 3H), 2.20-3.56 (m, 5H), 3.85 (s, 3H), 4.23-4.28 (m, 2H), 6.70 (s, 1H), 6.77-6.85 (d, 1H), 7.72-8.03 (d, 1H).
85%	With sodium hydride

77%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran Reflux; Stage #2: Diethyl carbonate In tetrahydrofuran for 25.5h; Reflux; Stage #3: With acetic acid In tetrahydrofuran; diethyl ether at 20℃;
70%	Stage #1: Diethyl carbonate With sodium hydride In toluene; mineral oil at 20 - 120℃; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In toluene; mineral oil at 120℃; Stage #3: With hydrogenchloride In toluene; mineral oil
57%	With sodium hydride In 1,2-dimethoxyethane at 85℃; for 2h;
	With sodium hydride
	With hydrogenchloride; acetic acid In tetrahydrofuran	8.a (a) (a) Ethyl 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate A solution of 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene (3 g) in tetrahydrofuran (30 ml) was added slowly to a solution of diethyl carbonate (5.85 ml) in tetrahydrofuran (150 ml) containing a suspension of sodium hydride (50% in oil, 3.28 g) over a period of 30 minutes. The mixture was treated at reflux with stirring, for 4 hours. Acetic acid (6 ml) then dilute HCl (20 ml) were added dropwise, and the bulk of the tetrahydrofuran removed by evaporation. The residue was taken up in ether (100 ml), washed with saturated brine and evaporated to give the sub-title compound as an orange oil (4.4 g).
	In N,N-dimethyl-formamide	P.4.1 (1) (1) Synthesis of 2-ethoxycarbonyl-6-methoxy-1-tetralone 6.29 g of diethyl carbonate was added to a DMF (50 ml) suspension containing 2.40 g of sodium hydride (about 60%, in oil). The mixture was heated to 60°C. Thereto was dropwise added a DMF (10 ml) solution containing 5.28 g of 6-methoxy-1-tetralone. The mixture was stirred at the same temperature for 2 hours. The reaction mixture was subjected to distillation to remove DMF. To the residue was added diluted hydrochloric acid. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by the use of a column to obtain 6.80 g of an intended product. 1H NMR (CDCl3, δ) 1.30 (3H, t), 2.29-2.51 (2H, m), 2.95-3.02 (2H, m), 3.53-3.58 (1H, m), 3.84 (3H, s), 4.23-4.28 (2H, m), 6.69 (1H, d), 6.84 (1H, dd), 8.02 (1H, d).
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In toluene Stage #2: Diethyl carbonate In toluene for 18h; Reflux;
	Stage #1: Diethyl carbonate With sodium hydride In toluene at 120℃; for 0.5h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In toluene at 120℃; for 12h;	27; XXXV Example 27 To a solution of XXXV-1A (7.4 g, 62.7 mmol) in toluene (100 mL) was added portion wise NaH (3.7 g, 92.5 mmol) at 25° C. and the mixture was heated at 120° C. for 30 min. Then to the mixture was added a solution of XXXV-1 (5.1 g, 18.5 mmol) in toluene (50 mL). The resulting mixture was stirred at 120° C. for 12 h. After being cooled to rt, aq. HCl (1M, 20 mL) was added to the mixture, and the mixture was extracted with EtOAc. The organics were combined, dried with Na2SO4, and concentrated to afford crude XXXV-2 (5.0 g, yield: 78.1%), which was used to next step directly.
	With potassium <i>tert</i>-butylate In tetrahydrofuran; ethanol Reflux;

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[2]Current Patent Assignee: RESEARCH TRIANGLE INSTITUTE - US2006/183743, 2006, A1 Location in patent: Page/Page column 6
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[8]Current Patent Assignee: SANOFI - US4670452, 1987, A
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[10]Location in patent: scheme or table Aboraia, Ahmed S.; Makowski, Bart; Bahja, Alba; Prosser, David; Brancale, Andrea; Jones, Glenville; Simons, Claire [European Journal of Medicinal Chemistry, 2010, vol. 45, # 10, p. 4427 - 4434]
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9
[ 74-88-4 ]
[ 1078-19-9 ]
[ 21568-65-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydride In benzene Heating;
100%	In benzene	4 2,2-dimethyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one PREPARATION 4 2,2-dimethyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one To a solution of 10 g (56 mmol) of 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one and 19.88 g(140 mmol) of methyl iodide in 32 mL benzene, were added, under argon atmosphere, 4.42 g (92 mmol) of 55% sodium hydride. The mixture was stirred at 60° C. for 5 h and then reflux for 2 h. The suspension was poured into methanol and the solvent was removed. The residue was dissolved in ether and washed with H2 O and Na2 CO3. The organic solution was dried over MgSO4 and the solvent was evaporated, yielding 11.20 g of the desired product as a colorless oil (yield: 100%). IR (film) ν: 2920, 1667, 1595, 1487, 1379, 1274, 1229, 1107, 1093 cm-1; 1 H NMR (80 MHz, CDCl3) δ (TMS): 7.99 (d, J=9 Hz, 1H, Ar), 6.80 (dd, J=9 Hz, J=2 Hz, 1H, Ar), 6.67 (broad s, 1H, AR), 3.82 (s, 3H, CH3 O), 2.93 (t, J=6.5 Hz, 2H, CH2 Ar), 1.94 (t, J=6.5 Hz, 2H, CH2), 1.19 (s, 6H, 2 CH3).
100%	With sodium hydride In benzene Heating / reflux;	5 REFERENCE EXAMPLE 5; 2,2-Dimethyl-6-methoxy-1 ,2,3,4-tetrahydronaphthalen-1 -one; To a suspension of sodium hydride (55% in mineral oil, 26.80 g, 0.55 mol) in benzene (159 ml_), 6-methoxy-1 ,2,3,4-tetrahydronaphthalen-1-one (50.00 g, 0.28 mol) and methyl iodide (99.10 g, 0.69 mol) were added. The mixture was heated to reflux overnight and allowed to cool to room temperature. After adding some drops of MeOH to destroy the excess of hydride, EtOAc and water were added.The phases were separated and the aqueous phase was reextracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was evaporated to afford the title compound (quantitative yield).1H NMR (80 MHz, CDCI3) δ (TMS): 1.19 (s, 6 H), 1.94 (t, J = 6.5 Hz, 2 H), 2.93 (t, J= 6.5 Hz, 2 H)1 3.82 (s, 3 H), 6.67 (broad s, 1 H), 6.80 (dd, J = 9 Hz, J1 =2 Hz, 1H), 7.99 (d, J = 9 Hz, 1 H).

100%	With sodium hydride In mineral oil; benzene Reflux;	5 Reference Example 5; 2,2-Dimethyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-oneTo a suspension of sodium hydride (55% in mineral oil, 26.80 g, 0.55 mol) in benzene (159 mL), 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one (50.00 g, 0.28 mol) and methyl iodide (99.10 g, 0.69 mol) were added. The mixture was heated to reflux overnight and allowed to cool to room temperature. After adding some drops of MeOH to destroy the excess of hydride, EtOAc and water were added. The phases were separated and the aqueous phase was reextracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was evaporated to afford the title compound (quantitative yield).1H NMR (80 MHz, CDCl3) 6 (TMS): 1.19 (s, 6H), 1.94 (t, J=6.5 Hz, 2H), 2.93 (t, J=6.5 Hz, 2H), 3.82 (s, 3H), 6.67 (broad s, 1H), 6.80 (dd, J=9 Hz, J'=2 Hz, 1H), 7.99 (d, J=9 Hz, 1H).
100%	With sodium hydride In benzene Heating / reflux;	5 REFERENCE EXAMPLE 5; 2,2-Dimethyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one; To a suspension of sodium hydride (55% in mineral oil, 26.80 g, 0.55 mol) in benzene (159 ml_), 6-methoxy-1 ,2,3,4-tetrahydronaphthalen-1-one (50.00 g, 0.28 mol) and methyl iodide (99.10 g, 0.69 mol) were added. The mixture was heated to reflux overnight and allowed to cool to room temperature. After adding some drops of MeOH to destroy the excess of hydride, EtOAc and water were added. The phases were separated and the aqueous phase was reextracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was evaporated to afford the title compound (quantitative yield). 1H NMR (80 MHz, CDCI3) δ (TMS): 1.19 (s, 6 H), 1.94 (t, J = 6.5 Hz, 2 H), 2.93 (t, J= 6.5 Hz, 2 H), 3.82 (s, 3 H), 6.67 (broad s, 1 H), 6.80 (dd, J = 9 Hz, J' =2 Hz, 1 H), 7.99 (d, J = 9 Hz, 1 H).
91%	With potassium <i>tert</i>-butylate In benzene for 3h; Ambient temperature;
90%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran for 1h; Cooling with ice; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 16h;	6-Methoxy-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one (8b) [25,27]: To a stirred solution of6-methoxy-3,4-dihydronaphthalen-1(2H)-one 7b (10.0 g, 56.8 mmol) dissolved in dry tetrahydrofuran(THF, 150 mL) in a 500 mL round bottomed flask was added NaH (11.4 g, 284 mmol, 60% in oil).After stirring the mixture for 1 h under ice-water bath, methyl iodide (32.3 g, 227 mmol) in dryTHF (50 mL) was added slowly. The mixture was allowed to stir at r.t. for 16 h. The reactionwas quenched by addition of water (slowly and dropwise). The mixture was then extractedwith ethyl acetate (3 100 mL), washed with water (2 100 mL), and dried over anhydrousNa2SO4. Evaporation of the solvent yielded a yellow oil. The residue was subjected to silica gelchromatography using petroleum ether (PE) and ethyl acetate (EtOAc) (10:1) as eluent to afford6-methoxy-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one 8b (10.4 g, yield 90%) as a yellow oil.1H-NMR (300 MHz, CDCl3) δ 7.99 (d, J = 8.7 Hz, 1H), 6.79 (dd, J = 8.8, 2.6 Hz, 1H), 6.65 (d, J = 2.5 Hz,1H), 3.81 (s, 3H), 2.92 (t, J = 6.4 Hz, 2H), 2.00-1.85 (m, 2H), 1.19 (s, 6H). 13C-NMR (75 MHz, CDCl3) δ 200.95, 162.86, 145.36, 129.76, 124.49, 112.84, 111.83, 54.84, 40.78, 36.30, 25.65, 24.06.
85%	With potassium hydroxide; 18-crown-6 ether In toluene at 70℃; for 2h;
80%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: methyl iodide In tetrahydrofuran at 20℃;	462.1 Step 1 : 6-methoxy-2,2-dimethyl-3.4-dihvdronaphthalen-1(2H)-one. 6-methoxy-l-tetralone (3.00 g, 17 mmol) was added to RBF followed by THF (20 mL). Sodium hydride (1.1 ml, 43 mmol) was added and the reaction was stirred at RT under nitrogen for 20 minutes. Gas evolution was observed. Iodomethane (2.7 ml, 43 mmol) was added via syringe and the reaction was stirred at RT overnight. The reaction was quenched with water (25 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and the residue was purified by column chromatography (0-10% EtOAc/Hexaϖe to provide the title compound as a white solid (2.77 g, 80% yield). MS m/z: 205.2 (M+l).
	With sodium hydride
	With potassium <i>tert</i>-butylate 1.) benzene, 0 deg C, 30 min, 2.) benzene, RT, 3 h; Yield given. Multistep reaction;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: methyl iodide In tetrahydrofuran at 40℃; for 0.5h;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 16h;	20.1 6-methoxy-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one To a solution of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1.0 g, 5.68 mmol) in anhydrous THF (7 mL) was added sodium hydride (442 mg, 9.6 mmol). After stirring at room temperature for 20 min, iodomethane ( 2.0 g, 14.2 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. The reaction was poured into water (10 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with (20 mL) and dried over Na2S04, filtered and concentrated in vacuo to afford crude oil product 1.17 g (99%). LCMS (ESI) m/z: 205.2 [M+H]+ . 1H-NMR (500 MHz, CDCl3): δ 8.02 (d, J= 9 Hz, 1H), 6.83 (s, 1H), 6.67 (d, J= 2.5 Hz, 1H), 3.85 (s, 3H), 2.95 (t, J= 6 Hz, 2H), 1.97 (t, J = 6 Hz, 2H), 1.20 (s, 6H)
13.4 g	With sodium hydride In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Almansa; Gomez; Cavalcanti; Rodriguez; Carceller; Bartroli; Garcia-Rafanell; Forn [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2121 - 2133]
[2]Current Patent Assignee: URIACH S.A. - US5208246, 1993, A
[3]Current Patent Assignee: PALAU PHARMA SA - WO2007/339, 2007, A1 Location in patent: Page/Page column 40
[4]Current Patent Assignee: PALAU PHARMA SA - US2010/222363, 2010, A1 Location in patent: Page/Page column 14
[5]Current Patent Assignee: PALAU PHARMA SA; URIACH S.A. - WO2007/337, 2007, A1 Location in patent: Page/Page column 32
[6]Murthy, A. Radha Krisna; Rao, G. S. R. Subba [Tetrahedron, 1982, vol. 38, # 22, p. 3335 - 3338]
[7]Wan, Chuan; Wang, Mingan; Yang, Dongyan; Han, Xiaoqiang; Che, Chuanliang; Ding, Shanshan; Xiao, Yumei; Qin, Zhaohai [Molecules, 2017, vol. 22, # 12]
[8]Oelgemoeller, Michael; Brem, Bernhard; Frank, Rudolf; Schneider, Siegfried; Lenoir, Dieter; Hertkorn, Norbert; Origane, Yumi; Lemmen, Peter; Lex, Johann; Inoue, Yoshihisa [Journal of the Chemical Society. Perkin Transactions 2 (2001), 2002, # 10, p. 1760 - 1771]
[9]Current Patent Assignee: AMGEN INC - WO2007/62007, 2007, A1 Location in patent: Page/Page column 205
[10]Hattersley,P.J. et al. [Journal of the Chemical Society C: Organic, 1969, p. 217 - 222]
[11]Collins, David J.; Jacobs, Howard A. [Australian Journal of Chemistry, 1986, vol. 39, # 12, p. 2095 - 2110]
[12]Nyangulu, James M.; Galka, Marek M.; Jadhav, Ashok; Gai, Yuanzhu; Graham, Cindy M.; Nelson, Ken M.; Cutler, Adrian J.; Taylor, David C.; Banowetz, Gary M.; Abrams, Suzanne R. [Journal of the American Chemical Society, 2005, vol. 127, # 6, p. 1662 - 1664]
[13]Current Patent Assignee: ROCHE HOLDING AG; XENON PHARMACEUTICALS INC - WO2014/144545, 2014, A2 Location in patent: Page/Page column 77; 78
[14]Takeuchi, Jun; Ohnishi, Toshiyuki; Okamoto, Masanori; Todoroki, Yasushi [Organic and Biomolecular Chemistry, 2015, vol. 13, # 14, p. 4278 - 4288]

10
[ 1730-48-9 ]
[ 1885-13-8 ]
[ 1078-19-9 ]

Reference： [1]Tetrahedron,1985,vol. 41,p. 4107 - 4118

11
[ 100-52-7 ]
[ 1078-19-9 ]
[ 50558-94-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydroxide In water Reflux;	General procedure for synthesis of 2 General procedure: Compound 2 is prepared by refluxing a mixture of 1-tetralone and aromatic aldehyde in aq. NaOH by the reported [20] procedure.
80%	With potassium hydroxide In methanol at 20℃; for 48h;
68%	With potassium hydroxide In ethanol for 4h; Ambient temperature;

64%	With toluene-4-sulfonic acid In ethanol for 24h; Reflux;
58%	With sodium hydroxide In water at 0 - 20℃; for 24h;

Reference： [1]Gautam, Deepika; Chaudhary [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015, vol. 135, p. 219 - 226]
[2]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]
[3]Tewari, S. C.; Rastogi, Shri Nivas [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 12, p. 1060 - 1064]
[4]Ranjbar, Sara; Akbari, Abdolhossein; Edraki, Najmeh; Khoshneviszadeh, Mahsima; Hemmatian, Hajar; Firuzi, Omidreza; Khoshneviszadeh, Mehdi [Letters in drug design and discovery, 2018, vol. 15, # 11, p. 1170 - 1179]
[5]Caleffi, Guilherme S.; Brum, Juliana De O. C.; Costa, Angela T.; Domingos, Jorge L. O.; Costa, Paulo R. R. [Journal of Organic Chemistry, 2021, vol. 86, # 6, p. 4849 - 4858]

12
[ 123-11-5 ]
[ 1078-19-9 ]
[ 72861-80-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium hydroxide In ethanol at 20℃; for 24h;	(E)-6-methoxy-2-(4-methoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one (3) A mixture of 6-methoxy-1-tetralone (1.76 g, 10 mmol) and 4-methoxybenzaldehyde (1.36 g, 1.22 mL, 10 mmol) in 4% ethanolicKOH (25 mL) was stirred at room temperature for 24 h. The reactionmixture was cooled to 0 C and the precipitate formed was filtered off,washed with 80% aqueous methanol, and finally recrystallized fromEthanol to obtain the corresponding arylidene (3).Yellow crystals; yield: 89%; m.p.: 143-145 C. 1H NMR (400 MHz,DMSO-d6): δ 7.91 (d, J = 8.6 Hz, 1H), 7.63 (s, 1H), 7.48 (d, J = 8.7 Hz,1H), 7.02 (d, J = 2.0 Hz, 1H), 7.00 (d, J = 2.0 Hz, 1H), 6.93 (dd, J = 8.7,2.6 Hz, 1H), 6.88 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 3.04 (t, J= 5.9 Hz, 2H), 2.88 (t, J = 6.5 Hz, 2H). 13C NMR (101 MHz, DMSO-d6):δ 185.74 (CO), 163.54 (6-benzo-C-OCH3), 160.02 (CH = CH-Ph-COCH3),146.15, 135.36 (Phe-CH = CH), 133.90 (Phe-CH = CH), 132.10,130.21, 128.18, 126.85, 114.47, 114.00, 112.65, 55.91 (OCH3), 55.65(OCH3), 28.64 (4-CH2), 27.11 (3-CH2); Anal. Calcd. for C19H18O3 (Exactmass: 294.13) as previously reported
89%	With potassium hydroxide In ethanol at 20℃; for 24h;	(E)-6-methoxy-2-(4-methoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one (3) A mixture of 6-methoxy-1-tetralone (1.76 g, 10 mmol) and 4-methoxybenzaldehyde (1.36 g, 1.22 mL, 10 mmol) in 4% ethanolicKOH (25 mL) was stirred at room temperature for 24 h. The reactionmixture was cooled to 0 C and the precipitate formed was filtered off,washed with 80% aqueous methanol, and finally recrystallized fromEthanol to obtain the corresponding arylidene (3).Yellow crystals; yield: 89%; m.p.: 143-145 C. 1H NMR (400 MHz,DMSO-d6): δ 7.91 (d, J = 8.6 Hz, 1H), 7.63 (s, 1H), 7.48 (d, J = 8.7 Hz,1H), 7.02 (d, J = 2.0 Hz, 1H), 7.00 (d, J = 2.0 Hz, 1H), 6.93 (dd, J = 8.7,2.6 Hz, 1H), 6.88 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 3.04 (t, J= 5.9 Hz, 2H), 2.88 (t, J = 6.5 Hz, 2H). 13C NMR (101 MHz, DMSO-d6):δ 185.74 (CO), 163.54 (6-benzo-C-OCH3), 160.02 (CH = CH-Ph-COCH3),146.15, 135.36 (Phe-CH = CH), 133.90 (Phe-CH = CH), 132.10,130.21, 128.18, 126.85, 114.47, 114.00, 112.65, 55.91 (OCH3), 55.65(OCH3), 28.64 (4-CH2), 27.11 (3-CH2); Anal. Calcd. for C19H18O3 (Exactmass: 294.13) as previously reported
76%	With toluene-4-sulfonic acid In ethanol for 24h; Reflux;

70%	With potassium hydroxide In ethanol for 4h; Ambient temperature;
47%	With sodium hydroxide In lithium hydroxide monohydrate at 0 - 20℃; for 24h;
	With potassium hydroxide In ethanol

Reference： [1]Abouzid, Khaled A. M.; Ahmed, Al-Shaimaa F.; Awad, Eman M.; Billon, Cyrielle; Daabees, Hoda; Elagawany, Mohamed; Elgendy, Bahaa; Kassab, Shaymaa E.; Ragab, Mahmoud A. [Bioorganic Chemistry, 2022, vol. 119]
[2]Abouzid, Khaled A. M.; Ahmed, Al-Shaimaa F.; Awad, Eman M.; Billon, Cyrielle; Daabees, Hoda; Elagawany, Mohamed; Elgendy, Bahaa; Kassab, Shaymaa E.; Ragab, Mahmoud A. [Bioorganic Chemistry, 2022, vol. 119]
[3]Ranjbar, Sara; Akbari, Abdolhossein; Edraki, Najmeh; Khoshneviszadeh, Mahsima; Hemmatian, Hajar; Firuzi, Omidreza; Khoshneviszadeh, Mehdi [Letters in drug design and discovery, 2018, vol. 15, # 11, p. 1170 - 1179]
[4]Tewari, S. C.; Rastogi, Shri Nivas [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 12, p. 1060 - 1064]
[5]Caleffi, Guilherme S.; Brum, Juliana De O. C.; Costa, Angela T.; Domingos, Jorge L. O.; Costa, Paulo R. R. [Journal of Organic Chemistry, 2021, vol. 86, # 6, p. 4849 - 4858]
[6]Devi Priya, Duraipandi; Mohana Roopan, Selvaraj [Synthetic Communications, 2020, vol. 50, # 12, p. 1813 - 1834]

13
[ 33513-42-7 ]
[ 1078-19-9 ]
[ 72019-91-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at -10℃; Reflux; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In N,N-dimethyl-formamide for 2h; Reflux; Stage #3: With water; sodium acetate In N,N-dimethyl-formamide
84%	With trichlorophosphate In dichloromethane at 27℃; for 2h;
75%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone at 0 - 95℃; for 5.083h;	1.1 (1) Preparation of compound 1 Add 5 mL of N,N-dimethylformamide (DMF) to a 25 mL two-necked flask, Then 2mL (20mmol) of phosphorus oxychloride (POCl3) was slowly added into a two-necked flask with a constant pressure funnel at 0 °C (the addition was completed within 5 minutes), After stirring for 30 minutes, add 0.2mL N,N-dimethylformamide and 0.3535g (2mmol) 6-methoxy-1-tetralone,After stirring for 5 minutes, the temperature is slowly raised to 9095°C, and stirring is continued for 5 hours to obtain a reaction liquid;A large number of viscous solids appeared after cooling with ice water, which was filtered under reduced pressure and vacuum dried to obtain compound 1 with a yield of 75%

51%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Inert atmosphere; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone at 0 - 80℃; for 2h;	6.6 6.6. Synthetic Method B; Preparation of 7-Methoxy-4,5-dihydronaphtho[1,2-b]thiophene-2-carboxylic acid and 6,7-difluoro-4,5-dihydronaptho[1,2-b]thiophene-2-carboxylic acid Under N2, phosphorous oxychloride (0.444 g, 2.90 mmol) was added drop-wise to DMF (1 mL) at 0° C. then stirred vigorously for 30 minutes. 6-Methoxy-3,4-dihydronaphthalen-1(2H)-one 5 (0.500 g, 2.83 mmol) was added at 0° C. and stirred at 0° C. for 30 minutes, followed by heating at 80° C. for 90 minutes. The reaction was cooled to room temperature, poured into a 25% aqueous NaOAc solution, and extracted with diethyl ether. The combined organic layers were washed with brine solution, dried over MgSO4 and concentrated in vacuo. The crude mixture was purified by silica gel chromatography (ethyl acetate-hexanes) to give 1-chloro-6-methoxy-3,4-dihydronaphthalene-2-carbaldehyde 6 (0.327 g, 1.46 mmol, 51% yield) as an orange solid. In some cases, the aldehyde could be carried to next step without chromatographic purification.
	With trichlorophosphate Yield given;
	With trichlorophosphate
	With trichlorophosphate for 5h;
	With trichlorophosphate at 60℃;

Reference： [1]Location in patent: experimental part LaFrate, Andrew L.; Gunther, Jillian R.; Carlson, Kathryn E.; Katzenellenbogen, John A. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 23, p. 10075 - 10084]
[2]Donkor; Gangjee; Kisliuk; Gaumont [Journal of Heterocyclic Chemistry, 1991, vol. 28, # 7, p. 1651 - 1655]
[3]Current Patent Assignee: XUCHANG UNIVERSITY - CN112876425, 2021, A Location in patent: Paragraph 0020; 0031-0036
[4]Current Patent Assignee: LEXICON PHARMACEUTICALS INC - US2012/302562, 2012, A1 Location in patent: Page/Page column 9
[5]Ramesh, D.; Kar, Gandhi K.; Chatterjee, Basanta G.; Ray, Jayanta K. [Journal of Organic Chemistry, 1988, vol. 53, # 1, p. 212 - 214]
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14
[ 298-12-4 ]
[ 1078-19-9 ]
[ 13587-70-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sulfuric acid In diethylene glycol dimethyl ether; water at 110℃;	1 2-(6-Methoxy-l-oxo-3,4-dihvdronaphthalen-2(lH)-ylidene)acetic acid (1A): 2-(6-Methoxy-l-oxo-3,4-dihvdronaphthalen-2(lH)-ylidene)acetic acid (1A): Glyoxalic acid (190 mL, 1702 mmol) and water (180 mL) were added to a stirred solution of 6- methoxy tetralone (300 g, 1702 mmol) in diglyme (600 mL) followed by sulfuric acid (80 mL, 1500 mmol). The reaction mixture was heated to 1 10 °C overnight. The reaction mixture was cooled to 0 °C, and resulting solids were filtered off and washed with water (3 x 200 mL), dried under reduced pressure to afford the title compound (350 g, 88%) as a solid. lH NMR (300 MHz, DMSO-i/6): δ 12.9 (bs, 1H), 7.9 (d, J= 8.4 Hz, 1H), 7.0 (m, 2H), 6.6 (s, 1H), 3.8 (s, 3H), 3.3 (m, 2H), 3.0 (m, 2H). ESI-MS m/z: 233 (M+H)+.
88%	With sulfuric acid In diethylene glycol dimethyl ether; water at 110℃;	1 2-(6-Methoxy-l-oxo-3,4-dihydronaphthalen-2(lH)-ylidene)acetic acid (1A) Glyoxalic acid (190 mL, 1.7 mol) and water (180 mL) were added to a stirred solution of 6-methoxytetralone (300 g, 1.7 mol) in diglyme (600 mL) followed by sulfuric acid (80 mL, 1.5 mol) and the reaction mixture was heated to 1 10 °C overnight. The reaction mixture was cooled to 0 °C and resulting solids were filtered off and washed with water (3 x 200 mL), dried under reduced pressure to afford the title compound (350 g, 88%) as a solid. lB NMR (300 MHz, DMSO-i/6): δ 12.9 (bs, 1H), 7.9 (d, J= 8.4 Hz, 1H), 7.0 (m, 2H), 6.6 (s, 1H), 3.8 (s, 3H), 3.3 (m, 2H), 3.0 (m, 2H). ESI-MS m/z: 233 (M+H)+.
85%	With sulfuric acid In diethylene glycol dimethyl ether at 85℃;	79 j0558] Glyoxalic acid (30 mE, 303 mmol) and water (14 mE) were added to a stirred solution of 6-methoxy tetralone (25 g, 141 mmol) in diglyme (50 mE) followed by sulphuric acid (6.5 mE, 35 mmol). The reaction mixture was heated to 85° C. overnight. The reaction mixture was cooled to 0° C., and resulting solids were filtered off and washed with water (3x25 mE), dried under reduced pressure to afford title compound (28 g, 85%) as solid. ‘H NMR (300 MHz, DMSO-d5):ö 12.9 (bs, 1H), 7.9 (d, J=8.4 Hz, 1H), 7.0(m, 2H), 6.6 (s, 1H), 3.8 (s, 3H), 3.3 (m, 2H), 3.0 (m, 2H). ESI-MS mlz: 233 (M+H).

85%	With sulfuric acid In diethylene glycol dimethyl ether; water at 85℃; for 15h;
30%	With acetic acid at 120℃;
	With sodium hydroxide In ethanol; water room temp., then 60 deg C;
	With sodium hydroxide In water for 3h; Ambient temperature;

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/74761, 2014, A2 Location in patent: Page/Page column 27
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/81995, 2014, A1 Location in patent: Page/Page column 17
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2015/307445, 2015, A1 Location in patent: Paragraph 0555; 0557 0558
[4]Cheung, Mui; Tangirala, Raghuram S.; Bethi, Sridhar R.; Joshi, Hemant V.; Ariazi, Jennifer L.; Tirunagaru, Vijaya G.; Kumar, Sanjay [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 103 - 108]
[5]Location in patent: scheme or table Josef, Kurt A.; Aimone, Lisa D.; Lyons, Jacquelyn; Raddatz, Rita; Hudkins, Robert L. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 12, p. 4198 - 4202]
[6]Ravina; Fueyo; Teran; Cid; Garcia Mera; Orallo; Bardan [Pharmazie, 1992, vol. 47, # 8, p. 574 - 577]
[7]Barlocco; Pinna; Carboni; Cipolla [Il Farmaco, 1989, vol. 44, # 10, p. 967 - 974]

15
[ 109-94-4 ]
[ 1078-19-9 ]
[ 16252-53-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium <i>tert</i>-butylate In toluene at -78 - -5℃; Inert atmosphere;	1.1.1 EXAMPLE 1; General procedure for α^α-formylation of tetralone IV into VIt is based on the work disclosed by B. C. Pearce, R. A. Parker, M. E. Deason, D. D. Dischino, E. Gillepsie, A. A. Qureshi, K. Volk, J. J. Kim Wright J. Med. Chem. 1994, 37, 526-541. A mixture of tetralone IV in toluene (1 eq, 0.45 mmol.mL"1) and ethyl formate (2.0 eq) was prepared. The solution was cooled to -78°C under Argon and mechanically stirred while potassium tert-butoxide (2.0 eq) was added in portions: the solution became milky and pinky. The solution was warmed to -5°C until TLC monitoring (petroleum ether / Et20: 3 / 1) indicated the completion of the reaction. The solution was quenched with 10% HCl (the pink solution disappeared) and the mixture extracted with Et20. The organic phases were dried (brine, MgS04) and concentrated in vacuo to yield alpha-formyl tetralone (usually as solid compound).Note: usually the product does not need to be further purified and can be directly engaged in the next step.1.1. 2-(hydroxymethylene)-6-methoxy-3,4-dihydronaphthalen-l(2H)-oneYield : >98% (light brown solid)1H NMR (200 MHz, CDC13) : δ = 2.51 (t, 2H, J = 7.3 Hz), 2.82 (t, 2H, J = 7.3 Hz), 3.82 (s, 3H), 6.68 (d, 1H, J= 2.4 Hz), 6.82 (dd, 1H, J= 8.6 Hz, 2.4 Hz), 7.91 (d, 1H, J= 8.6 Hz), ppmThe spectroscopic and physical data were identical to those reported in the literature (S. H. Kim, J. R. Gunther, J. A. Katzenellenbogen Org. Lett. 2008, 10, 4931-4934).
98%	Stage #1: formic acid ethyl ester; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With potassium <i>tert</i>-butylate at -78 - -5℃; Inert atmosphere; Stage #2: With hydrogenchloride In water	1; 1.1 EXAMPLE 1 General procedure for alpha-formylation of tetralone IV into V General procedure: It is based on the work disclosed by B. C. Pearce, R. A. Parker, M. E. Deason, D. D. Dischino, E. Gillepsie, A. A. Qureshi, K. Volk, J. J. Kim Wright J. Med. Chem. 1994, 37, 526-541. [0052] A mixture of tetralone IV in toluene (1 eq, 0.45 mmol.ML-1) and ethyl formate (2.0 eq) was prepared. The solution was cooled to -78°C under Argon and mechanically stirred while potassium tert-butoxide (2.0 eq) was added in portions: the solution became milky and pinky. The solution was warmed to -5°C until TLC monitoring (petroleum ether / Et2O: 3 / 1) indicated the completion of the reaction. The solution was quenched with 10% HCl (the pink solution disappeared) and the mixture extracted with Et2O. The organic phases were dried (brine, MgSO4) and concentrated in vacuo to yield alpha-formyl tetralone (usually as solid compound). [0053] Note: usually the product does not need to be further purified and can be directly engaged in the next step. Yield : >98% (light brown solid) [0056] 1H NMR (200 MHz, CDCl3) : δ = 2.51 (t, 2H, J = 7.3 Hz), 2.82 (t, 2H, J = 7.3 Hz), 3.82 (s, 3H), 6.68 (d, 1H, J = 2.4 Hz), 6.82 (dd, 1H, J = 8.6 Hz, 2.4 Hz), 7.91 (d, 1H, J = 8.6 Hz), ppm [0057] The spectroscopic and physical data were identical to those reported in the literature (S. H. Kim, J. R. Gunther, J. A. Katzenellenbogen Org. Lett. 2008, 10, 4931-4934).
98%	With potassium <i>tert</i>-butylate In toluene at -78 - -5℃; Inert atmosphere;

96%	With potassium <i>tert</i>-butylate In toluene at -78 - 20℃;
92%	With sodium methylate In benzene for 7h; Ambient temperature;
92%	With sodium hydride In mineral oil; benzene
86%	With sodium methylate In benzene for 24h; Ambient temperature;
85%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil for 4h; Inert atmosphere; Stage #2: formic acid ethyl ester In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil for 20h; Inert atmosphere;	4.3.1.3 6-Methoxy-2-hydroxymethylen-3,4-dihydro-2H-naphthalen-1-one (1) To a stirred solution of sodium hydride (27 mg, of 60 % dispersion in oil, 1.13 mmol) in 2 mL of dry DMF under an N2 atmosphere, a solution of 6-methoxy-1-tetralone (0.20 g,1.13 mmol) in 2 mL of dry THF was added dropwise. After being stirred for 4 h, ethyl formate (0.1 mL, 1.25 mmol) was added and the mixture was stirred for an additional 20 h.A saturated solution of NH4Cl was added to quench the reaction mixture, and the product was extracted twice with ethyl acetate (2 × 15 mL). The joint organic layers were evaporated under vacuum, and the resulting orange solid was chromatographed (20 % EtOAc-hexanes) to give 0.18 g of the desired product as amorphous yellow solid in 85 % yield. M.p. 95-96 °C (lit: 93 °C [26] and 97-100 °C [27]). - IR (KBr): 1688,3211 cm-1. - 1H NMR (400 MHz, CDCl3): δ = 2.52 (t, J = 6.6Hz, 2H, 3-H), 2.85 (t, J = 6.6 Hz, 2H, 4-H), 3.83 (s, 3H, CH3O),6.71 (d, J = 2.2 Hz, 1H, 5-H), 6.84 (dd, J = 8.7, 2.2 Hz, 1H, 7-H),7.93 (m, 2H, C = CH, 8-H), 14.70 (br s, 1H, OH) ppm. - 13C NMR(400 MHz, CDCl3): δ = 25.2, 28.4, 60.3, 114.2, 130.9, 166.7,168.9 (-C = C-OH), 185.6 (C = O) ppm. - Anal. for C12H12O3(204.2): calcd. C 70.57, H 5.92; found: C 70.44, H 6.01.
	With sodium ethanolate In pyridine
	With sodium methylate
	With hydrogenchloride In toluene	1 2-Hydroxymethylene-6-Methoxy-1-Tetralone (2) EXAMPLE 1 2-Hydroxymethylene-6-Methoxy-1-Tetralone (2) A mixture of 6-methoxy-1-tetralone (1) (20 g, 0.113 mole) and ethyl formate (16.82 g, 0.23 mole) were dissolved in about 250 mL of toluene. The solution was cooled to about -78° C. under nitrogen and mechanically stirred while potassium t-butoxide (25.5 g, 0.23 mole) was added in portions giving rise to a reddish colored solution. The mixture was slowly warmed to about -5° over a period of about one hour at which time TLC analysis (1:1 EtOAc:Hexanes) indicated a complete conversion to the less polar product. The reaction mixture was quenched with about 10% HCl and extracted with ether. The ether extracts were dried (brine, MgSO4) and concentrated in vacuo to yield 24.4 g of a dark brown oil. The oil was purified by distillation in a Kugelrohr oven [bath temp. 160°-180°/0.1 mm Hg] to yield the title compound as a yellow oil (22.6 g, 0.11 mole, 98% yield) that solidified on standing [mp 66°-68°, (Lit. Kieboom et al., Synthesis, 476-478, (1970)), mp 68°-69°].

Reference： [1]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - WO2012/131010, 2012, A1 Location in patent: Page/Page column 66-67
[2]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - EP2505583, 2012, A1 Location in patent: Paragraph 0051-0057
[3]Rodo, Elena Cesar; Feng, Liwen; Jida, Mouhamad; Ehrhardt, Katharina; Bielitza, Max; Boilevin, Jérémy; Lanzer, Michael; Williams, David Lee; Lanfranchi, Don Antoine; Davioud-Charvet, Elisabeth [European Journal of Organic Chemistry, 2016, vol. 2016, # 11, p. 1982 - 1993]
[4]Maeta, Naoya; Kamiya, Hidehiro; Okada, Yohei [Organic Letters, 2019, vol. 21, # 21, p. 8519 - 8522]
[5]Collins; Cullen; Fallon; Gatehouse [Australian Journal of Chemistry, 1984, vol. 37, # 11, p. 2279 - 2294]
[6]Kim, Sung Hoon; Gunther, Julian R.; Katzenellenbogen, John A. [Organic Letters, 2008, vol. 10, # 21, p. 4931 - 4934]
[7]Collins, David J.; Fallon, Gary D.; Skene, Colin E. [Australian Journal of Chemistry, 1994, vol. 47, # 4, p. 623 - 648]
[8]Kasiotis, Konstantinos M.; Tzanetou, Evangelia N.; Stagos, Dimitrios; Fokialakis, Nikolas; Koutsotheodorou, Eleni; Kouretas, Dimitrios; Haroutounian, Serkos A. [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2015, vol. 70, # 9, p. 677 - 690]
[9]Kieboom,A.P.G.; van Bekkum,H. [Synthesis, 1970, p. 476 - 478]
[10]Bhattacharya, Sudin; Mandal, Asok N.; Chaudhuri, Swadesh R. Ray; Chatterjee, Amareshwar [Journal of the Chemical Society. Perkin transactions I, 1984, # 1, p. 5 - 13]
[11]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US5204373, 1993, A

16
[ 50-00-0 ]
[ 1078-19-9 ]
[ 27752-24-5 ]

Reference： [1]Tetrahedron,1988,vol. 44,p. 81 - 90

17
[ 7677-24-9 ]
[ 1078-19-9 ]
[ 80859-07-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With zinc(II) chloride
64%	With zinc(II) iodide for 48h; Ambient temperature;
56%	With zinc(II) iodide In toluene; acetonitrile at 60℃; for 5h;	VI To a stirred mixture of compound VI- 1 (10 g, 57 mmol) and Znl2 (0.2 g) in toluene/CH3CN (v/v=3: l, 100 mL) was added TMSCN (7.3 g, 73.8 mmol). The mixture was stirred at 60°C for 5 hrs. Then the mixture was diluted with EtOAc (100 mL), the organic layer was separated, washed with water and brine, dried over Na2S04 and concentrated. The residue was purified by column chromatography on silica gel to give product VI-2 (8.8 g, yield 56%). MS (ESI) m/z (M+H)+ 276.1.

With zinc(II) iodide

Reference： [1]Beeley, Nigel R. A.; Cremer, Gerard; Dorlhene, Alain; Mompon, Bernard; Pascard, Claudine; Tran Huu Dau, Elise [Journal of the Chemical Society. Chemical communications, 1983, # 18, p. 1046 - 1048]
[2]Belletire, J. L.; Howard, H.; Donahue, K. [Synthetic Communications, 1982, vol. 12, # 10, p. 763 - 770]
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2013/25733, 2013, A1 Location in patent: Paragraph 0445
[4]Itani, Hiromichi; Ito, Harunobu; Sakata, Yoshihiko; Hatakeyama, Yoshifumi; Oohashi, Hiroko; Satoh, Yoshinari [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 757 - 761]

18
[ 358-23-6 ]
[ 1078-19-9 ]
[ 115375-59-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In dichloromethane at 0 - 40℃; for 24h; Sealed tube; Inert atmosphere;	General Procedure B: Synthesis of Trifluoromethanesulfonates General procedure: To an oven dried 25 mL round-bottomed flask was added 1-tetralone (600 mg, 4.1 mmol, 1equiv). The flask was sealed and purged with N2 before addition of CH2Cl2 (16.5 mL, 0.25M) and Et3N (0.86 mL, 6.2 mmol, 1.5 equiv). The reaction mixture was cooled to 0 °C andtrifluoromethanesulfonic anhydride (1 mL, 6.2 mmol, 1.5 equiv) was added dropwise undernitrogen before it was heated to 40 °C and maintained at this temperature with stirring for 24h. Upon completion of the reaction, the solution was washed with water (2 x 20 mL) and theorganics passed through a hydrophobic frit and concentrated under reduced pressure to give abrown oil, which was purified by flash chromatography (silica gel, 0-5% Et2O in petroleumether) to afford the title compound as a yellow oil (1.15 g, quant.).
70%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at 0 - 20℃;
69%	With triethylamine In dichloromethane at 0℃; for 22h; Inert atmosphere; Reflux;	2.1. General Procedure A: Triflation of tetralones General procedure: For example, the preparation of 6-methoxy-3,4-dihydronaphthalen-1-yl trifluoromethanesulfonate (1a)-6-Methoxy-1-tetralone (2.00 g, 11.35 mmol, 1 equiv) was weighed into an oven-dried flask.The flask was sealed and purged with N2 before the addition of CH2Cl2 (45 mL, 0.25 M). The reaction was cooled to 0 °C and triflic anhydride (3.8 mL, 22.7 mmol, 2 equiv) and Et3N (3.2mL, 22.7 mmol, 2 equiv) were added dropwise via syringe sequentially. The reaction mixture was then heated to reflux for 22 h with stirring. After the reaction was complete, the reaction was allowed to cool to room temperature and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica gel, 0-5% EtOAc in petroleum ether)to afford the desired product as a yellow oil (2.41 g, 69%).

62%	With 2,6-di-tert-butyl-4-methylpyridine In dichloromethane for 7h; Ambient temperature;
	With Cs₂CO₃ In 1,4-dioxane; toluene regioselective reaction;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With 2-chloropyridine In dichloromethane at 0℃; for 0.166667h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at 0 - 20℃; Inert atmosphere;

Reference： [1]Wilson, Kirsty L.; Murray, Jane; Jamieson, Craig; Watson, Allan J. B. [Synlett, 2018, vol. 29, # 5, p. 650 - 654]
[2]Chang, Dalu; Gu, Yang; Shen, Qilong [Chemistry - A European Journal, 2015, vol. 21, # 16, p. 6074 - 6078]
[3]Cain, David L.; McLaughlin, Calum; Molloy, John J.; Carpenter-Warren, Cameron; Anderson, Niall A.; Watson, Allan J. B. [Synlett, 2019, vol. 30, # 7, p. 787 - 791]
[4]Arcadi, Antonio; Cacchi, Sandro; Marinelli, Fabio [Tetrahedron, 1993, vol. 49, # 22, p. 4955 - 4964]
[5]Wu, Zhao; Xu, Xiaolong; Wang, Jianchun; Dong, Guangbin [Science, 2021, vol. 374, # 6568, p. 734 - 740]
[6]Gong, Li; Li, Chao; Liu, Senlin; Yuan, Fangyan; Zeng, Xiaoming [Organic Letters, 2022, vol. 24, # 17, p. 3227 - 3231]

19
[ 1083-11-0 ]
[ 676-58-4 ]
[ 1078-19-9 ]
[ 83669-11-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1982,vol. 19,p. 545 - 550

20
[ 39959-51-8 ]
[ 1078-19-9 ]
[ 98799-48-5 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 4933 - 4938

21
[ 25384-14-9 ]
[ 1078-19-9 ]
[ 83876-53-3 ]

Reference： [1]Journal of Medicinal Chemistry,1983,vol. 26,p. 303 - 306

22
[ 39232-91-2 ]
[ 1078-19-9 ]
[ 3200-42-8 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 380 - 386

23
[ 39232-91-2 ]
[ 1078-19-9 ]
6,11-dihydro-4,8-dimethoxy-5H-benzo<a>carbazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 380 - 386

24
[ 1078-19-9 ]
[ 20933-24-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With tetra-N-butylammonium tribromide In methanol; dichloromethane at 20℃;
88%	With bromine In diethyl ether for 3h;	1 2-BROMO-6-METHOXY-3,4-DIHYDRO-2H-NAPHTHALEN-1-ONE (3) 6-Methoxy-1-tetralone 1 (100 g, 0.567 mole) was dissolved in ethyl ether (2 liters) and treated with a dropwise addition of Br2 (30 ml, 0.59 mole) over a 1 hour period. The solution was stirred for two additional hours and then worked up by washing with a 10% Na2SO3 solution, NaHCO3 and brine. The solution was allowed to set overnight and 30 grams of crystals filtered off the following day. The remaining solution was concentrated to yield an additional 98 grams of product. The combined yield of the desired product was 128 g (88%). The material was used "as is" for subsequent reactions.
84%	With phenyltrimethylammonium tribromide In tetrahydrofuran at -78 - 20℃; for 17h; Inert atmosphere;	10 5.1.10. (2RS)-2-Bromo-6-methoxy-3,4-dihydronaphthalen-1(2H)-one(10a) To a solution of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one(9a, 35.6 g, 200 mmol) in THF (600 mL) was added a solution ofphenyltrimethylammonium tribromide (76.4 g, 200 mmol) in THF(400 mL) at 78 C for 1 h under N2 atmosphere. After stirring at78 C to room temperature (rt) for 4 h and at rt for 12 h., the precipitationwas collected off and washed with EtOAc. The filtrate wasconcentrated under reduced pressure. The residue was cooled withrefrigerator. The precipitation was collected off and washed withiPr2O to obtain 10a (42.9 g, 84%) as white powder. Furthermore,the recrystallization form n-hexane/iPr2O gave colorless plate. 1HNMR (CDCl3) d 2.33-2.60 (2H, m), 2.87 (1H, ddd, J = 17.0 Hz,4.5 Hz, 4.2 Hz), 3.30 (1H, ddd, J = 17.0 Hz, 9.8 Hz, 6.1 Hz), 3.87(3H, s), 4.69 (1H, dd, J = 4.2 Hz, 4.2 Hz), 6.72 (1H, d, J = 2.7 Hz),6.87 (1H, dd, J = 9.1 Hz, 2.7 Hz), 8.07 (1H, d, J = 9.1 Hz); IR (KBr)cm1 3007, 2943, 2909, 2839, 1680, 1599, 1568, 1495, 1462,1454, 1443, 1435, 1429, 1352, 1319, 1302, 1261, 1215, 1194,1159, 1124, 1113, 1086, 1034, 1016, 995, 930; Anal. Calcd forC11H11O2Br: C, 51.79; H, 4.35. Found: C, 51.75; H, 4.28.

80%	With triphenylphosphine hydrobromide; dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; chemoselective reaction;
74%	With copper(ll) bromide In chloroform; ethyl acetate for 2h; Heating;
	With hydrogenchloride; bromine In tetrachloromethane; diethyl ether
	With n-butyllithium; bromine; 1,1,1,3,3,3-hexamethyl-disilazane 1.) THF, hexane, -78 deg C, 1 h; 2.) THF, hexane, -78 deg C, 2 h; 3.) THF, hexane, -78 deg C, 5 min; Yield given. Multistep reaction;
	With copper(I) bromide
	With N-Bromosuccinimide; toluene-4-sulfonic acid at 60℃; for 0.166667h;
	With bromine	6 2 -Bromo-6-methoxytetralone PREPARATION 6 2 -Bromo-6-methoxytetralone 6-Methoxytetralone (2.0 g, 11.4 mmol) and bromine (0.6 ml, 11.7 mmol) were refluxed in ether (50 ml) for 30 minutes. The reaction mixture was cooled, concentrated, the residue partitioned between ethyl acetate and dilute NaHSO3. The organic layer was washed with saturated NaHCO3 and water, dried over CaSO4, and concentrated to an oil (2.83 g, 100%); 1 H-NMR 8.03 (d, J=9.0 Hz, 1H), 6.84 (dd, J1 =9.0 Hz, J2 =2.7 Hz, 1H), 6.69 (d, J=2.3 Hz, 1H), 4.66 (t, J=4.1 Hz, 1H), 3.84 (s,3H), 3.20-3.30 (m, 1H), 2.82-2.90 (m, 1H), 2.34-2.50 (m, 2H).
	With 1,1'-(ethane-1,2-diyl)dipyridinium bistribromide In acetonitrile for 0.166667h;
	With N-Bromosuccinimide; toluene-4-sulfonic acid at 80℃; for 0.166667h;
	With copper(ll) bromide In 1,2-dichloro-ethane at 75℃; Heating; Reflux; Inert atmosphere;	1 A lO L flask was fitted with two cooling condensers and a dry pipe. 6.75 L of 1,2- dichloroethane and 750 grams of 6-methoxy-l-tetralone were added and stirred to get a brown transparent liquid. The temperature was raised to 75 °C, then 47 Ig Of CuBr2 was added over a period of 30 min. The mixture was heated to reflux for 2 hrs and a further 337.5g of CuBr2added. After reflux overnight, the color had changed to yellowish-green- gray. HPLC revealed that 10% starting material still remained; a further 100 g OfCuBr2 was added and stirred for 3 hours to complete the reaction.The reaction was cooled to room temperature, filtered, and the filter cake was washed with 1 ,2-dichloroethane (750 mL x 2), and the mother liquid was washed with NaHCO3 (1500 mL x 4), then washed with brine (750 mL x 2). The organic layer was dried with Na2SO4 and de-colored with active carbon. The liquid was maintained at a temperature lower than 90 °C, concentrated under vacuum, and cooled to 50 °C. Methanol was added, the solution decolorized with charcoal, filtered, and washed with 300 mL methanol. The liquids were combined, cooled to 0-5 °C for 30 min, filtered, then washed with 150 mL methanol. The cake was dried to obtain 940 g of 2-bromo-6-methoxy-3,4- dihydronaphthalen-l(2H)-one, M=255.2, purity 98.48%.
	With bromine In diethyl ether at 20℃;	20.A EXAMPLE 20Preparation of Methyl [(2S)- 1 - { (2S)-2- [4-(8- { 2-[(2S)- 1 - { (2^)-2-[(methoxycarbonyl)amino] -3 - methylbutanoyl } pyrrolidin-2-yl] - lH-imidazol-5 -yl } -5 , 6-dihydrobenzo [£]naphtho [2, 1- 2 (4.7 g, 29.3 mmol). The resulting reaction was allowed to stir for 2 hours at room temperature, then the reaction mixture was washed with 10% Na2S203, brine, dried over Na2S04, filtered and concentrated in vacuo to provide Int- 20a which was used without further purification. MS (ESI) m/e (M+H) +: 256.
	With bromine In diethyl ether at 20℃;	20.A EXAMPLE 20Preparation of Methyl [(2S)- 1 - { (2S)-2- [4-(8- { 2-[(2S)- 1 - { (2^)-2-[(methoxycarbonyl)amino] -3 - methylbutanoyl } pyrrolidin-2-yl] - lH-imidazol-5 -yl } -5 , 6-dihydrobenzo [£]naphtho [2, 1- 2 (4.7 g, 29.3 mmol). The resulting reaction was allowed to stir for 2 hours at room temperature, then the reaction mixture was washed with 10% Na2S203, brine, dried over Na2S04, filtered and concentrated in vacuo to provide Int- 20a which was used without further purification. MS (ESI) m/e (M+H) +: 256.
	With N-Bromosuccinimide; toluene-4-sulfonic acid at 60℃; for 0.183333h;
	With bromine	6 2-Bromo-6-methoxytetralone PREPARATION 6 2-Bromo-6-methoxytetralone 6-Methoxytetralone (2.0 g, 11.4 mmol) and bromine (0.6 ml, 11.7 mmol) were refluxed in ether (50 ml) for 30 minutes. The reaction mixture was cooled, concentrated, the residue partitioned between ethyl acetate and dilute NaHSO3. The organic layer was washed with saturated NaHCO3 and water, dried over CaSO4, and concentrated to an oil (2.83 g, 100%); 1 H-NMR 8.03 (d, J=9.0Hz, 1H), 6.84 (dd, J1 =9.0 Hz, J2 =2.7 Hz, 1H), 6.69 (d, J=2.3 Hz, 1H), 4.66 (t, J=4.1Hz, 1H), 3.84 (s,3H), 3.20-3.30 (m, 1H), 2.82-2.90 (m, 1H), 2.34-2.50 (m, 2H).
	With N-Bromosuccinimide; toluene-4-sulfonic acid In dichloromethane for 4h; Reflux;

Reference： [1]Voets, Marieke; Antes, Iris; Scherer, Christiane; Müller-Vieira, Ursula; Biemel, Klaus; Marchais-Oberwinkler, Sandrine; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2006, vol. 49, # 7, p. 2222 - 2231]
[2]Current Patent Assignee: PFIZER INC - US2006/4087, 2006, A1 Location in patent: Page/Page column 11; 16
[3]Imaeda, Toshihiro; Ono, Koji; Nakai, Kazuo; Hori, Yasunobu; Matsukawa, Jun; Takagi, Terufumi; Fujioka, Yasushi; Tarui, Naoki; Kondo, Mitsuyo; Imanishi, Akio; Inatomi, Nobuhiro; Kajino, Masahiro; Itoh, Fumio; Nishida, Haruyuki [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 14, p. 3719 - 3735]
[4]Mal, Kanchan; Sharma, Abhinandan; Maulik, Prakas R.; Das, Indrajit [Chemistry - A European Journal, 2014, vol. 20, # 3, p. 662 - 667]
[5]Hobbs-Mallyon, David; Li, Warren; Whiting, Donald A. [Journal of the Chemical Society. Perkin transactions I, 1997, # 10, p. 1511 - 1516]
[6]Kasturi,T.R.; Arunachalam,T. [Canadian Journal of Chemistry, 1968, vol. 46, p. 3625 - 3629]
[7]Posner, Gary H.; Switzer, Christopher [Journal of the American Chemical Society, 1986, vol. 108, # 6, p. 1239 - 1244]
[8]Kamila, Sukanta; Mukherjee, Chandrani; Mondal, Sasanka S.; De, Asish [Tetrahedron, 2003, vol. 59, # 8, p. 1339 - 1348]
[9]Pravst, Igor; Zupan, Marko; Stavber, Stojan [Tetrahedron Letters, 2006, vol. 47, # 27, p. 4707 - 4710]
[10]Current Patent Assignee: PFIZER INC - US5356905, 1994, A
[11]Murru, Siva; Singh; Kavala, Veerababurao; Patel, Bhisma K. [Tetrahedron, 2008, vol. 64, # 8, p. 1931 - 1942]
[12]Pravst, Igor; Zupan, Marko; Stavber, Stojan [Tetrahedron, 2008, vol. 64, # 22, p. 5191 - 5199]
[13]Current Patent Assignee: BIOGEN IDEC INC. - WO2010/51031, 2010, A1 Location in patent: Page/Page column 22
[14]Current Patent Assignee: MERCK & CO INC - WO2012/41227, 2012, A1 Location in patent: Page/Page column 106
[15]Current Patent Assignee: MERCK & CO INC - WO2012/40924, 2012, A1 Location in patent: Example 20
[16]Xiao, Hai-Yun; Watterson, Scott H.; Langevine, Charles M.; Srivastava, Anurag S.; Ko, Soo S.; Zhang, Yanlei; Cherney, Robert J.; Guo, Wei-Wei; Gilmore, John L.; Sheppeck, James E.; Wu, Dauh-Rurng; Li, Peng; Ramasamy, Duraisamy; Arunachalam, Piramanayagam; Mathur, Arvind; Taylor, Tracy L.; Shuster, David J.; McIntyre, Kim W.; Shen, Ding-Ren; Yarde, Melissa; Cvijic, Mary Ellen; Marino, Anthony M.; Balimane, Praveen V.; Yang, Zheng; Banas, Dana M.; Cornelius, Georgia; D'Arienzo, Celia J.; Warrack, Bethanne M.; Lehman-McKeeman, Lois; Salter-Cid, Luisa M.; Xie, Jenny; Barrish, Joel C.; Carter, Percy H.; Dyckman, Alaric J.; Murali Dhar [Journal of Medicinal Chemistry, 2016, vol. 59, # 21, p. 9837 - 9854]
[17]Current Patent Assignee: PFIZER INC - US5436255, 1995, A
[18]Pan, Jianke; Wu, Jia-Hong; Zhang, Hongkui; Ren, Xiaoyu; Tan, Jian-Ping; Zhu, Lixiang; Zhang, Hong-Su; Jiang, Chunhui; Wang, Tianli [Angewandte Chemie - International Edition, 2019, vol. 58, # 22, p. 7425 - 7430][Angew. Chem., 2019, vol. 131, p. 7503 - 7508,6]

25
[ 1078-19-9 ]
[ 1885-13-8 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1982,vol. 324,p. 550 - 556

26
[ 1078-19-9 ]
[ 3648-86-0 ]
[ 22245-89-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 53% 2: 15%	With hydrogenchloride; sodium azide In water at 0 - 50℃;
1: 13% 2: 50%	With sodium azide; methanesulfonic acid at 0 - 20℃; for 24h;
1: 49% 2: 27%	With sodium azide; trichloroacetic acid at 70℃; for 4h;	E.1 To a heated solution of 6-methoxy-1-tetalone (1G) in trichloroacetic acid (10g) is added sodium azide (553mg) at 70C, and the mixture is maintaining with stirring for 4h. The reaction mixture is diluted with ice water and neutralized with potassium carbonate, and extracted with ethyl acetate. The organic layer is successively washed with water and saturated NaCI aq, dried over MgS04, concentrated in vacuo. The crude product is purified by silica gel column chromatography to give 7-methoxy-2,3, 4,5-tetrahydro-benzo [c] azepin- 1-one (later) in 49% yield and 7-methoxy-1,3, 4,5-tetrahydro-benzo [b] azepin-2-one in 27% yield.

1: 48% 2: 35%	With sodium azide; trichloroacetic acid at 60℃;
1: 38% 2: 21%	With sodium azide; sulfuric acid In toluene at 0 - 20℃;
	With sodium azide; methanesulfonic acid at 20℃; for 18h;
	Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium acetate / ethanol / 2 h / Reflux 2: polyphosphoric acid / 2 h / 95 °C
1: 47.6 %Chromat. 2: 23.1 %Chromat.	With sodium azide; methanesulfonic acid In neat (no solvent) at 6 - 8℃;

Reference： [1]Location in patent: experimental part Crosby, Ian T.; Shin, James K.; Capuano, Ben [Australian Journal of Chemistry, 2010, vol. 63, # 2, p. 211 - 226]
[2]Wang, Xiao-Feng; Guan, Fang; Ohkoshi, Emika; Guo, Wanjun; Wang, Lili; Zhu, Dong-Qing; Wang, Sheng-Biao; Wang, Li-Ting; Hamel, Ernest; Yang, Dexuan; Li, Linna; Qian, Keduo; Morris-Natschke, Susan L.; Yuan, Shoujun; Lee, Kuo-Hsiung; Xie, Lan [Journal of Medicinal Chemistry, 2014, vol. 57, # 4, p. 1390 - 1402]
[3]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2004/69256, 2004, A1 Location in patent: Page/Page column 31
[4]Nicholls; Alewood [Bioorganic Chemistry, 1994, vol. 22, # 3, p. 300 - 317]
[5]Location in patent: experimental part Crosby, Ian T.; Shin, James K.; Capuano, Ben [Australian Journal of Chemistry, 2010, vol. 63, # 2, p. 211 - 226]
[6]Dalence-Guzman, Maria F.; Berglund, Magnus; Skogvall, Staffan; Sterner, Olov [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 5, p. 2499 - 2512]
[7]Crosby, Ian T.; Shin, James K.; Capuano, Ben [Australian Journal of Chemistry, 2010, vol. 63, # 2, p. 211 - 226]
[8]Piao, Feng-Yu; Xie, Yu-Zhong; Zhang, Wen-Bin; Zhang, Wei; Han, Rong-Bi [Synthetic Communications, 2013, vol. 43, # 14, p. 1920 - 1930]

27
[ 93340-26-2 ]
[ 40463-28-3 ]
[ 1078-19-9 ]

Reference： [1]Journal of Chemical Research, Miniprint,1988,p. 2856 - 2876

28
[ 1078-19-9 ]
[ 13587-99-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: methyl-triphenylphosphonium iodide With sodium hydride In dimethyl sulfoxide at 20 - 75℃; for 1.33333h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In dimethyl sulfoxide at 65 - 70℃; for 8h;	1 6-Methoxy-1-methylene-1,2,3,4-tetrahydro-naphthalene (27) 6-Methoxy-1-methylene-1,2,3,4-tetrahydro-naphthalene (27) To a dry 500 mL 3-necked round bottom flask equipped with a reflux condenser and magnetic stir bar, was charged sodium hydride (3.0 g, 172.89 mmol). The reaction flask was put under nitrogen, and 35 mL of anhydrous DMSO was added. The reaction mixture was heated to 70-75° C., and stirred at that temperature until the evolution of hydrogen ceased. The reaction mixture was cooled to room temperature and additional 25 mL of DMSO was added. Methyltriphenylphosphonium iodide (46.57 g, 115.26 mmol) was added in portions over a period of 1 h. 25 mL of additional DMSO was added to facilitate easy stirring. After the completion of addition, the reaction mixture was stirred for 20 minutes. 6-methoxytetralone (10.156 g, 57.63 mmol) dissolved in 10 mL of anhydrous DMSO was added to reaction mixture. Then, the reaction mixture was heated to 60-65° C., and stirred at that temperature for 8 h. The reaction mixture was poured into a 500 mL Erlenmeyer flask containing 150 mL of crushed ice and 150 mL of hexanes. The resulting mixture was stirred vigorously for 15 min, and then extracted with hexanes. The combined organic layers were washed DMSO:Water (1:1) and then dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. Purification by flash column chromatography (silica gel 3:97 EtOAc:Hexanes) yielded 9.42 g of 27 as white solid (94%). Rf: 0.71, (30:70, EtOAc:Hexanes). 1H NMR (CDCl3, 300 MHz): δ 7.8 (d, J=8.73 Hz, 1H), δ 6.74 (dd, J=8.72 Hz, 2.74 Hz, 1 H), δ 6.62 (d, J=2.71 Hz, 1 H), δ 5.34 (s, 1H), δ 4.84 (s, 1 H), δ3.76 (s, 3H), δ 2.81 (t, J=6.27 Hz, 2 H), δ 2.53 (t, J=6.34, 2H), δ 1.87 (p, J=6.16, 2 H).
	With Methyltriphenylphosphonium bromide; sodium tert-pentoxide In benzene Heating;

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2006/293394, 2006, A1 Location in patent: Page/Page column 24
[2]Moreau,C.; Rouessac,F. [Bulletin de la Societe Chimique de France, 1973, p. 3427 - 3432]

29
[ 74-88-4 ]
[ 1078-19-9 ]
[ 27752-24-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In toluene; at 80℃; for 72h;	A mixture of 6-methoxy-1-tetralone (5.0 g, 28.4 mmol), methyl iodide (20 mL, 262 mmol) and sodium hydride (60%, 5.5 g, 138 mmol, prewashed twice with hexanes) in toluene is heated at 80 0C for 3 days. The mixture is quenched carefully with water and is partitioned between EtOAc and brine. The organic extract is dried with MgSO4, concentrated and purified via column chromatography to give the title compound as a light yellow oil: 1H NMR (CDCI3) delta 1.27 (d, J = 7 Hz, 3H), 1.83-1.89 (m, 1 H), 2.10-2.15 (m, 1 H), 2.51-2.60 (m, 1H), 2.90-3.00 (m, 2H), 3.85 (s, 3H), 6.68 (s, 1H), 6.81 (d, J = 8.6 Hz, 1 H), 8.01 (d, J = 8.6 Hz, 1 H).

Reference： [1]Organic Letters,2013,vol. 15,p. 5000 - 5003
[2]Journal of the American Chemical Society,2013,vol. 135,p. 15306 - 15309
[3]European Journal of Organic Chemistry,2002,p. 181 - 187
[4]Journal of medicinal chemistry,1970,vol. 13,p. 314 - 317
[5]Patent: WO2007/67615,2007,A2 .Location in patent: Page/Page column 86
[6]Organic Letters,2019,vol. 21,p. 6884 - 6887

30
[ 1779-49-3 ]
[ 1078-19-9 ]
[ 13587-99-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: Methyltriphenylphosphonium bromide With sodium hydride In tetrahydrofuran; n-heptane; dimethyl sulfoxide; mineral oil at 20℃; for 0.5h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran; n-heptane; dimethyl sulfoxide; mineral oil for 4h;	1.1 Preparation No.1: 5-Benzyl-2-methoxy-8,9-dihydro-5H-benzo[7]annulen-6(7H)-one (4, R2=Benzyl)Step No.1: 6-Methoxy-1-methylene-1,2,3,4-tetrahydronaphthalene (2)Step 1 was performed according to methods described by Michael W. Justik and Gerald F. Koser in Molecules 2005, 10, 217-225. Thus, into a 1 L 3-neck flask outfitted with a mechanical stirrer and addition funnel was added a suspension of sodium hydride (60% in mineral oil, 9.99 g, 250 mmol). The sodium hydride was washed with heptane (3×75 mL) and dry DMSO (163 mL) was added. The reaction was heated at about 60° C. for about 1 h and then cooled to rt. The reaction was diluted with THF (160 mL) and methyltriphenylphosphonium bromide (91.0 g, 256 mmol) was added in one portion. The reaction was stirred for about 30 min, then a solution of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (22.0 g, 125 mmol) in THF (85 mL) was added dropwise. The reaction was stirred for about 4 h, then poured into water (1000 mL) and extracted with Et2O (3×500 mL). The combined Et2O extracts were washed with water (500 mL), dried over Na2SO4, filtered and concentrated. The residue was extracted several times with 10% EtOAc in heptane (5×50 mL). The combined extracts were concentrated and the residue was purified on silica gel (200 g) using a gradient from 0-15% EtOAc in heptane. The product fractions were combined, concentrated and dried to constant weight to yield 6-methoxy-1-methylene-1,2,3,4-tetrahydronaphthalene (2) (21.5 g, 95%) as an oil. LC/MS, method 1, Rt=0.90 min, no parent ion. 1H NMR (400 MHz, DMSO-d6) δ 7.57 (d, J=8.7 Hz, 1H), 6.71 (dd, J=8.7, 2.8 Hz, 1H), 6.65 (d, J=2.7 Hz, 1H), 5.36 (d, J=1.1 Hz, 1H), 4.81 (d, J=1.4 Hz, 1H), 3.73 (s, 3H), 2.75 (t, J=6.2 Hz, 2H), 2.46-2.37 (m, 2H), 1.78-1.71 (m, 2H).
70%	Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 2h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran at 0 - 20℃;	10.1 (1) Preparation of 6-methoxy-1-methylene-1,2,3,4-tetrahydronaphthalene Ph3P+CH3Br- (2.64g, 7.40mmol)Soluble in 15ml tetrahydrofuran,At 0 ° C,Partial addition of potassium t-butoxide(0.83g, 7.40mmol),After the addition was completed, the mixture was stirred at room temperature for 2 h.6-methoxy-3,4-dihydronaphthalene-1(2H)-one was added dropwise at 0 °C(1.0g, 5.70mmol)Tetrahydrofuran solution (10ml),After 15 minutes,The reaction was allowed to rise to room temperature overnight.The reaction solution was filtered through celite.Dry the solvent,Column chromatography (eluent: petroleum ether: ethyl acetate = 50:1) yielded 0.7 g of colorless transparent liquid.Yield: 70%.
	(i) BuLi, hexane, Et₂O, (ii) /BRN= 972739/; Multistep reaction;

	With potassium <i>tert</i>-butylate In diethyl ether for 20h; Ambient temperature;
	Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 0.5h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran at 50℃; for 3h; Inert atmosphere;	Method A General procedure: To a 100 mL round bottom flask equipped with a Teflon coated stir bar was added methyltriphenylphosphonium bromide (15 mmol, 1.5 equiv) and THF (40 mL). The reaction mixture was cooled to 0 C and stirred. Once cooled, KOtBu (15 mmol, 1.5 equiv) was added and the system was removed from the ice bath and let stir at room temperature for 0.5 h. Next, ketone (10 mmol, 1 equiv) was added to the system which was then purged with N2 and heated to 50 °C for 3 h. Upon completion, the reaction was quenched with water (20 mL), extracted with ether (250 mL), and dried with sufficient MgSO4. The resulting extracts were concentrated in vacuo and purified via flash column chromatography.

Reference： [1]Current Patent Assignee: ABBVIE INC; ABBOTT LABORATORIES INC - US2012/238549, 2012, A1 Location in patent: Page/Page column 29
[2]Current Patent Assignee: GUANGZHOU HENOVCOM BIOSCIENCE - CN108341822, 2018, A Location in patent: Paragraph 0196; 0200-0202
[3]Strike; Jen; Hughes; Douglas; Smith [Steroids, 1966, vol. 8, # 3, p. 309 - 317]
[4]Ohta, Tetsuo; Ikegami, Hiroshi; Miyake, Tsutomu; Takaya, Hidemasa [Journal of Organometallic Chemistry, 1995, vol. 502, # 1-2, p. 169 - 176]
[5]Ritz, Mikhaila D.; Parsons, Astrid M.; Palermo, Philip N.; Jones, William D. [Polyhedron, 2020, vol. 180]

31
[ 37595-74-7 ]
[ 1078-19-9 ]
[ 115375-59-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.75h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 0℃; for 3h;
89%	With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; for 16h; Inert atmosphere;
80%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 20℃; Inert atmosphere;

38%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at 20℃; Inert atmosphere;	30.1 Step 1. 6-methoxy-3 ,4-dihydronaphthalen- 1 -yl trifluoromethanesulfonate Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 6-methoxy- 1,2,3 ,4-tetrahydronaphthalen- 1-one (500 mg, 2.84 mmol, 1.00 equiv) in tetrahydrofuran (14 mL). This was followed by the addition of LHIVIDS (1M in tetrahydrofuran) (4.3 mL) at -78 °C. The mixture was stirred for lh at -78 °C. To this was added phenyl [(trifluoromethane) sulfonyloxy] amino trifluoromethanesulfonate (1.52 g, 3.90 mmol, 1.90 equiv). The resulting solution was stirred overnight at room temperature (20 °C). The resulting solution was diluted with 40 mL of EA, washed with brine (100 mL x 2) and of sat. NH4C1 (100 mL x 2), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was applied onto a silica gel column with EA:PE (0-10%). The collected fraction was concentrated to give 330 mg (38%) of 6-methoxy-3,4- dihydronaphthalen-1-yl trifluoromethanesulfonate as a yellow solid. MS (ES, m/z): 309 [M+H]
	With lithium hexamethyldisilazane 1.) THF, -78 deg C, 1 h, 2.) THF, -78 deg C to RT, 1 h; Yield given. Multistep reaction;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 20℃; for 2h;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 20℃; Inert atmosphere;
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 0℃; for 3h;

Reference： [1]Richmond, Edward; Duguet, Nicolas; Slawin, Alexandra M. Z.; Lebl, Tomas; Smith, Andrew D. [Organic Letters, 2012, vol. 14, # 11, p. 2762 - 2765]
[2]Lou, Terry Shing-Bong; Bagley, Scott W.; Willis, Michael C. [Angewandte Chemie - International Edition, 2019, vol. 58, # 52, p. 18859 - 18863][Angew. Chem., 2019, vol. 131, # 52, p. 19035 - 19039,5]
[3]Hamze, Abdallah; Brion, Jean-Daniel; Alami, Mouad [Organic Letters, 2012, vol. 14, # 11, p. 2782 - 2785]
[4]Current Patent Assignee: THE ROCKEFELLER UNIVERSITY - WO2017/123518, 2017, A1 Location in patent: Paragraph 0109
[5]Pal [Synthesis, 1995, # 12, p. 1485 - 1487]
[6]Torrado, Alicia; Lamas, Carlos; Agejas, Javier; Jiménez, Alma; Díaz, Nuria; Gilmore, Jeremy; Boot, John; Findlay, Jeremy; Hayhurst, Lorna; Wallace, Louise; Broadmore, Richard; Tomlinson, Rosemarie [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 20, p. 5277 - 5295]
[7]Hon, Yung-Son; Tseng, Tze-Wei; Cheng, Chia-Yi [Chemical Communications, 2009, # 37, p. 5618 - 5620]
[8]Cai, Guilong; Zhou, Zhibing; Wu, Wenchao; Yao, Bo; Zhang, Shaowen; Li, Xiaofang [Organic and Biomolecular Chemistry, 2016, vol. 14, # 37, p. 8702 - 8706]

32
[ 51516-96-2 ]
[ 1078-19-9 ]
3-methoxy-9-nitro-5,11-dihydro-6H-benzo[a]carbazole [ No CAS ]

Reference： [1]Il Farmaco,1996,vol. 51,p. 75 - 78

33
[ 24743-11-1 ]
[ 13185-18-7 ]
[ 1078-19-9 ]

Reference： [1]Organic Preparations and Procedures International,1997,vol. 29,p. 477 - 480

34
[ 74-88-4 ]
[ 1078-19-9 ]
[ 27752-24-5 ]
[ 21568-66-1 ]

Reference： [1]Tetrahedron,1997,vol. 53,p. 15771 - 15786

35
[ 16821-32-2 ]
[ 1078-19-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With 1-hydroxy-1H-1,2,3-benziodoxathiole 1,3,3-trioxide; Oxone; cetyltrimethylammonim bromide In water at 20℃; for 2h; Green chemistry; chemoselective reaction;	IBS-catalysed alcohol oxidation in CTAB micelle; general procedure General procedure: The alcohol (2 mmol) was added to a solution of IBS (0.02 mmol, 0.01 eq), oxone (2.2 mmol, 1.1 equiv.) and 3 wt% CTAB solution (5 mL). The mixture was stirred at room temperature. The reaction was monitored by TLC. After completion, the solution was extracted with CH2Cl2 (3 × 10 mL). The combined organic phase was then filtered through a pad of silica gel and evaporated under vacuum to afford the desired product.
93%	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In water at 25℃; for 24h; Micellar solution;	General procedure for the oxidation of alcohols General procedure: A vial was charged with alcohol (1 mmol), IBX (1.2 mmol, 1.2 equiv) and 2 wt % GMPGS-2000/H2O solution (5 mL). The mixture was stirred for 24 h at 25 °C and filtered. The solid was washed with CH2Cl2 and the filtrate was extracted with CH2Cl2 (3×10 mL). Then, the organic phase was combined and dried with anhydrous Na2SO4, evaporated to dryness. The crude product was purified was purified by column chromatography on silica gel eluted with (petroleum ether/EtOAc) to afford the desired product.
92%	With diisopropyl-carbodiimide In toluene at 120℃; for 24h; Inert atmosphere; Sealed tube;

90%	With oxygen In N,N-dimethyl-formamide at 20℃; for 6h; UV-irradiation;	Photocatalytic oxidation of benzyl alcohols by 3D-RGO/ZnO photocatalyst General procedure: A 25 mL round-bottomed flask was charged with alcohol (1 mmol),3D-RGO/ZnO (40 mg) and N,N-dimethyl formamide (5 mL). The resultant mixture was stirred under O2 with two white LED lamps (12W). After completion of the reaction, the 3D-RGO/ZnO catalyst was recycled by filtration and the organic phase of the filtrate was extracted with EtOAc, washed three times with water and dried over Na2SO4.The pure product was then isolated by silica chromatography using petroleum ether/EtOAc mixtures as the eluent.
82%	With chromium(VI) oxide; tert.-butylhydroperoxide; silica gel In dichloromethane for 0.166667h; microwave irradiation;
75%	With iodine; potassium carbonate; potassium iodide at 90℃; for 0.5h;
65%	With iodine; hydrazine hydrate; dimethyl sulfoxide In water; acetonitrile at 80℃; for 6h;
93 %Spectr.	With C₃₉H₃₇N₆OPRu⁽²⁺⁾2F₆P^(1-)CH₂Cl₂; potassium <i>tert</i>-butylate In toluene at 100℃; for 0.5h;

Reference： [1]Liu, Yangyang; Wang, Boliang [Journal of Chemical Research, 2014, vol. 38, # 7, p. 427 - 431]
[2]Xie, Aming; Zhou, Xiangxiang; Feng, Liandong; Hu, Xinyu; Dong, Wei [Tetrahedron, 2014, vol. 70, # 21, p. 3514 - 3519]
[3]Sueki, Shunsuke; Matsuyama, Mizuki; Watanabe, Azumi; Kanemaki, Arata; Katakawa, Kazuaki; Anada, Masahiro [European Journal of Organic Chemistry, 2020, vol. 2020, # 31, p. 4878 - 4885]
[4]Wang, Yuxiang; Zhang, Xianlong; Wang, Lihua; Chen, Youjian [Journal of Chemical Research, 2015, vol. 39, # 12, p. 727 - 730]
[5]Singh; Sharma; Chhibber; Kaur; Kad [Synthetic Communications, 2000, vol. 30, # 21, p. 3941 - 3945]
[6]Gogoi, Pranjal; Konwar, Dilip [Organic and Biomolecular Chemistry, 2005, vol. 3, # 19, p. 3473 - 3475]
[7]Gogoi, Pranjal; Sarmah, Gautam Kumar; Konwar, Dilip [Journal of Organic Chemistry, 2004, vol. 69, # 15, p. 5153 - 5154]
[8]Naziruddin, Abbas Raja; Zhuang, Chun-Shiuan; Lin, Wan-Jung; Hwang, Wen-Shu [Dalton Transactions, 2014, vol. 43, # 14, p. 5335 - 5342]

36
methyllithium-lithium bromide [ No CAS ]
[ 1078-19-9 ]
[ 27752-24-5 ]
1-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydronaphthalene [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 9241 - 9244

37
[ 325723-04-4 ]
[ 1078-19-9 ]
[ 1769-84-2 ]
6-Methoxy-2,2-diphenyl-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2000,p. 3775 - 3778

38
[ 867-13-0 ]
[ 1078-19-9 ]
(6-methoxy-3,4-dihydro-2<i>H</i>-[1]naphthyliden)-acetic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.3%	With sodium hydride In tetrahydrofuran at 20 - 60℃; for 4h; Inert atmosphere;	Step A: To the solution of 6-methoxy-3,4-dihydronaphthalen-l(2H)-one(5.0mmol, 0.88Ig) in THF (25.OmL) was added NaH (12.5mmol, 0.5Og) and then ethyl 2- (diethoxyphosphoryl) acetate (12.5mmol, 2.5mL) under nitrogen at room temperature. The reaction mixture was heated at 60 0C for four hours. The reaction was cooled and quenched with water, extracted with EtOAc. The organic layer was washed with water, brine and dried over Na2SO4.The solvent was removed under reduced pressure and chromato graphed (Silica gel, 30% EtOAc in Hexanes.) to give compound (266) (0.792g, 64.3%). LC-MS ESI m/z found 247.0 [M+H]+.
64.3%	With sodium hydride In tetrahydrofuran at 0℃; Reflux; Inert atmosphere;	10.A [0291] Step A: Sodium hydride (0.5 g, 12.5 mmol) was added slowly to a mixture of 6- methoxy-l-tetralone (0.881 g, 5.0 mmol) and triethyl phosphonoacetate (2.5 mL, 12.5 mmol) in anhydrous tetrahydrofuran (25 mL) at 0 °C. The reaction was warmed to room temperature and refluxed under nitrogen for 48 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase was washed with water, brine, dried with sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (40% EtOAc in hexanes) to provide ethyl 2-(6-methoxy-3,4-dihydronaphthalen-l(2H)-ylidene)acetate (512) (0.792 g, 64.3%) as a yellow oil.
64.3%	With sodium hydride In tetrahydrofuran at 0℃; Reflux; Inert atmosphere;	10.A [0283] Step A: Sodium hydride (0.5 g, 12.5 mmol) was added slowly to a mixture of 6- methoxy-1-tetralone (0.881 g, 5.0 mmol) and triethyl phosphonoacetate (2.5 mL, 12.5 mmol) in anhydrous tetrahydrofuran (25 mL) at 0 0C. The reaction was warmed to room temperature and refluxed under nitrogen for 48 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase was washed with water, brine, dried with sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (40% EtOAc in hexanes) to provide ethyl 2- (6-methoxy-3,4-dihydronaphthalen-l(2H)-ylidene)acetate (512) (0.792 g, 64.3%) as a yellow oil.

	With sodium hydride In various solvent(s)
	With sodium hydride In toluene Reflux;

Reference： [1]Current Patent Assignee: CYMABAY THERAPEUTICS, INC. - WO2010/48207, 2010, A2 Location in patent: Page/Page column 90
[2]Current Patent Assignee: CYMABAY THERAPEUTICS, INC. - WO2011/159297, 2011, A1 Location in patent: Page/Page column 93
[3]Current Patent Assignee: CYMABAY THERAPEUTICS, INC. - WO2010/80537, 2010, A1 Location in patent: Page/Page column 68
[4]Berardi, Francesco; Ferorelli, Savina; Colabufo, Nicola Antonio; Leopoldo, Marcello; Perrone, Roberto; Tortorella, Vincenzo [Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 5, p. 1325 - 1335]
[5]Location in patent: scheme or table Negoro, Nobuyuki; Sasaki, Shinobu; Ito, Masahiro; Kitamura, Shuji; Tsujihata, Yoshiyuki; Ito, Ryo; Suzuki, Masami; Takeuchi, Koji; Suzuki, Nobuhiro; Miyazaki, Junichi; Santou, Takashi; Odani, Tomoyuki; Kanzaki, Naoyuki; Funami, Miyuki; Tanaka, Toshimasa; Yasuma, Tsuneo; Momose, Yu [Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1538 - 1552]

39
[ 105-36-2 ]
[ 1078-19-9 ]
[ 87901-81-3 ]

Reference： [1]Chemical Research in Toxicology,2002,vol. 15,p. 332 - 342

40
[ 1078-19-9 ]
[ 128557-02-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -78 - 45℃; for 18h;
71%	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -78℃; for 20h; Inert atmosphere; Reflux;
61%	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -78℃; for 20h; Inert atmosphere; Reflux;

60%	With phosphorus tribromide In benzene at 80℃;
	With phosphorus tribromide In benzene at 60℃; Inert atmosphere;
	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -60 - 20℃; for 20h; Inert atmosphere; Reflux;
	With triphenyl phosphite; bromine; triethylamine In dichloromethane at -60 - 50℃; for 18h; Inert atmosphere;
	With triphenyl phosphite; bromine; triethylamine In dichloromethane at 20℃; for 12h; Inert atmosphere;	10.1 Step 1: Synthesis of intermediate WX010-2 At room temperature and under nitrogen atmosphere, triphenyl phosphite (96.85 g, 312.13 mmol, 82.07 mL)was dissolved in dichloromethane (1000 mL), cooled to -78 °C, and then liquid bromine (54.41 g, 340.50 mmol, 17.55mL) was added dropwise, and then triethylamine (368.88 mmol, 51.34 mL) was added dropwise. The reaction mixturewas stirred and reacted for 30 minutes, then the compound WX010-1 (50 g, 283.75 mmol) was added, and the reactionmixture was returned to room temperature and stirred and reacted for 12 hours. After completion of the reaction, thereaction solution was poured into saturated aqueous sodium sulfite solution (1500 mL), and extracted with dichloromethane(1000 mL 3 3). The organic phase was combined, washed with saturated brine (1000 mL 3 3) successively, driedover anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to remove the solvent.The resulting residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate = 1/0, volume ratio)to obtain intermediate WX010-2. 1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J = 8.8 Hz, 1H), 6.75 (dd, J = 2.2, 8.6 Hz, 1H),6.67 (d, J = 2.4 Hz, 1H), 6.30 (t, J = 4.8 Hz, 1H), 3.82 (s, 3H), 2.82 (t, J = 7.8 Hz, 2H), 2.41-2.28 (m, 2H).

Reference： [1]Egami, Hiromichi; Hamashima, Yoshitaka; Masuda, Kousuke; Niwa, Tomoki; Rouno, Taiki; Yamashita, Kenji [Angewandte Chemie - International Edition, 2020, vol. 59, # 33, p. 14101 - 14105][Angew. Chem., 2020, vol. 132, # 33, p. 14205 - 14209,5]
[2]Lukamto, Daniel H.; Gaunt, Matthew J. [Journal of the American Chemical Society, 2017, vol. 139, # 27, p. 9160 - 9163]
[3]Romanov-Michailidis, Fedor; Romanova-Michaelides, Maria; Pupier, Marion; Alexakis, Alexandre [Chemistry - A European Journal, 2015, vol. 21, # 14, p. 5561 - 5583]
[4]Shagufta; Raghunandan, Resmi; Maulik, Prakas R.; Panda, Gautam [Tetrahedron Letters, 2005, vol. 46, # 32, p. 5337 - 5341]
[5]Singh, Ritesh; Panda, Gautam [RSC Advances, 2013, vol. 3, # 42, p. 19533 - 19544]
[6]Olivares, Astrid M.; Weix, Daniel J. [Journal of the American Chemical Society, 2018, vol. 140, # 7, p. 2446 - 2449]
[7]Kang, Jun-Chen; Tu, Yong-Qiang; Dong, Jia-Wei; Chen, Chao; Zhou, Jia; Ding, Tong-Mei; Zai, Jian-Tao; Chen, Zhi-Min; Zhang, Shu-Yu [Organic Letters, 2019, vol. 21, # 8, p. 2536 - 2540]
[8]Current Patent Assignee: WUXI APPTEC CO., LTD. - EP3848363, 2021, A1 Location in patent: Paragraph 0144-0145

41
[ 7654-06-0 ]
[ 1078-19-9 ]
[ 851366-70-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydride In dimethyl sulfoxide at 25℃; for 6h;
91%	With sodium hydride In dimethyl sulfoxide at 25℃; Inert atmosphere;	2.i FIG. 12 shows Scheme 2, the synthesis of Chemosensor (12). (i) NaH, DMSO, 25° C., N2 (g), 91%; ii. 8-hydroxyquinoline-2-carbaldehyde, TFA, DCM, 25° C., N2 (g); iii. p-chloranil, DCM, 25° C., N2 (g); iv. TEA, BF3-OEt2, 25° C., N2 (g), 25% (for ii., iii., iv.).
91%	With sodium hydride In dimethyl sulfoxide at 25℃; for 6h; Inert atmosphere;

80%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In dimethyl sulfoxide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 3-phenyl-2H-azirine In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere;
80%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 0.5h; Stage #2: 3-phenyl-2H-azirine In dimethyl sulfoxide; mineral oil at 0 - 20℃; for 1h;
25.8%	With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 3h;

Reference： [1]Mei, Yujiang; Bentley, Paul A.; Wang, Wei [Tetrahedron Letters, 2006, vol. 47, # 14, p. 2447 - 2449]
[2]Current Patent Assignee: STC.UNM (in: University of New Mexico); UNIVERSITY OF NEW MEXICO - US7994311, 2011, B2 Location in patent: Page/Page column 7
[3]Shrestha, Pradeep; Dissanayake, Komadhie C.; Gehrmann, Elizabeth J.; Wijesooriya, Chamari S.; Mukhopadhyay, Atreyee; Smith, Emily A.; Winter, Arthur H. [Journal of the American Chemical Society, 2020, vol. 142, # 36, p. 15505 - 15512]
[4]Zhou, Effie Y.; Knox, Hailey J.; Liu, Chang; Zhao, Weili; Chan, Jefferson [Journal of the American Chemical Society, 2019, vol. 141, # 44, p. 17601 - 17609]
[5]Yadav, Anuj K.; Tapia Hernandez, Rodrigo; Chan, Jefferson [Methods in Enzymology, 2021, vol. 657, p. 415 - 441]
[6]Müller, Bernhard J.; Borisov, Sergey M.; Klimant, Ingo [Advanced Functional Materials, 2016, vol. 26, # 42, p. 7697 - 7707]

42
[ 1078-19-9 ]
methyl halide [ No CAS ]
[ 27752-24-5 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 1721 - 1724

43
[ 1867-38-5 ]
[ 1078-19-9 ]
[ 893618-25-2 ]

Yield	Reaction Conditions	Operation in experiment
72%	With piperidine In ethanol for 5h; Heating;
65%	With piperidine In ethanol at 130℃; for 0.25h; Microwave irradiation;	2.3.2. General procedure for the synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenyl (or substituted phenyl)-4H-benzo [h]chromene-3-carbonitrile 2a-e General procedure: A mixture of 2-substituted arylidenemalononitriles (0.001 mol),namely; 2-Benzylidene malononitrile, 2-((furan-2-yl) methylene)malononitrile, 2-(4-chlorobenzylidene) malononitrile, 2-(3,4,5-trimethoxybenzylidene) malononitrile, or 2-(4-methoxybenzylidene) malononitrile, in ethanol (3 mL), were addedto a mixture of 6-methoxy-1-tetralone (1) (0.001 mol), and fewdrops of piperidine. The reaction mixture was subjected to microwaveirradiation at 130 C, (400W) for ~ 15 min. Completion of thereaction (was monitored by TLC). After cooling the product wasfiltered, and recrystallized from dilute ethanol to give compounds2a-e.

Reference： [1]Jachak; Kendre; Avhale; Toche; Medhane [Organic Preparations and Procedures International, 2006, vol. 38, # 3, p. 313 - 324]
[2]Haiba, Mogedda E.; Al-Abdullah, Ebtehal S.; Ahmed, Nesreen S.; Ghabbour, Hazem A.; Awad, Hanem M. [Journal of Molecular Structure, 2019, vol. 1195, p. 702 - 711]

44
[ 1867-38-5 ]
[ 1078-19-9 ]
[ 929698-66-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With ammonium acetate; acetic acid In ethanol for 5h; Heating;
86%	With ammonium acetate; acetic acid In ethanol for 12h; Reflux;	General Procedure to Obtain Derivatives 4-7(a-m) General procedure: A solution of tetralone (2.0 mmol) and benzylidenemalononitrile (3.08 mmol) respectives in ethanol 10 mL and acetic acid catalytic amount was refluxed for 12h. The solid formed on cooling was collected, washed with diethyl ether and recrystallized from ethanol.
65%	With piperidine; ammonium acetate In ethanol at 130℃; for 0.25h; Microwave irradiation;	2.3.12. General procedure for the synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenyl (or substituted phenyl) benzo [h] quinoline-3-carbonitrile 6a-e General procedure: A mixture of suitable 2-substituted arylidenemalononitriles(0.001 mol), namely; 2-Benzylidene malononitrile, 2-((furan-2-yl)methylene) malononitrile, 2-(4-chlorobenzylidene) malononitrile,2-(3,4,5-trimethoxybenzylidene) malononitrile, and/or 2-(4-methoxybenzylidene) malononitrile, in ethanol (3 mL), wereadded to a mixture of 6-methoxy-1-tetralone (1) (0.001 mol),ammonium acetate (0.002 mol), and few drops of piperidine. Thereaction mixture was subjected to microwave irradiation at 130 C,(400W) for ~ 15 min. Completion of the reaction (was monitored byTLC), after cooling the product was filtered, and recrystallized fromdilute ethanol to give compounds 6a-e.

Reference： [1]Jachak; Kendre; Avhale; Toche; Medhane [Organic Preparations and Procedures International, 2006, vol. 38, # 3, p. 313 - 324]
[2]Mata, Gricelda; Rodrigues, Juan; Gamboa, Neira; Charris, Katiuska; Lobo, Gricela; Monasterios, Melina; Avendaño, Milagros; Lein, Michael; Jung, Klaus; Abramjuk, Claudia; Nitzsche, Bianca; Höpfner, Michael; Charris, Jaime [Letters in drug design and discovery, 2017, vol. 14, # 4, p. 398 - 413]
[3]Haiba, Mogedda E.; Al-Abdullah, Ebtehal S.; Ahmed, Nesreen S.; Ghabbour, Hazem A.; Awad, Hanem M. [Journal of Molecular Structure, 2019, vol. 1195, p. 702 - 711]

45
[ 1078-19-9 ]
[ 3648-86-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium azide; sulfuric acid In acetic acid at 0 - 5℃; for 4h; Reflux;
60%	With sodium azide In hydrogenchloride; water at 0 - 20℃;	General Procedure for the Preparation of the Benzolactams 3, 4, and 17-21 by Schmidt Reaction General Procedure: To an ice-cooled solution of the benzocycloketone (1.4 mmol) in 1:1 CH2Cl2/methanesulfonic acid (10 mL) (except for compound 17, where concentrated HCl was used as solvent), sodium azide (0.2g, 2.8 mmol) was added in portions. The resulting mixture was allowed to stir at 0 °C for 1h, and then warmed up to room temperature while stirring overnight. Then, the reaction mixture was poured into ice-water (20 mL), basified with 5M NaOH (aq) until pH 9, and extracted with CH2Cl2 (3 × 10 mL). The organic layers were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude lactam. Purification on silicagel chromathography (1:1 AcOEt/Hexane → AcOEt) provided the desired 2H-benzolactam. The isomeric 1H benzolactam was also isolated in lower yield.
50%	With sodium azide; methanesulfonic acid

	With sodium azide; sulfuric acid In toluene
	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With trimethylsilylazide In trifluoroacetic acid at 20℃; for 168h; Stage #2: With sodium carbonate In water; ethyl acetate; trifluoroacetic acid	57.A A. 7-Methoxy-2,3,4,5-tetrahydro-2-benzazepin-1-one 7-Methoxy-2,3,4,5-tetrahydro-2-benzazepin-1-one A solution of 6-methoxy-3,4-dihydro-2H-naphthalen-1-one (5.28 g, 30 mmol) in 50 mL of TFA is treated with trimethylsilylazide (5.2 mL, 39 mmol) at RT. After 7 days, the reaction is quenched with ice, then diluted with water while stirring. The product is taken up in EtOAc, and the organic solution is washed with aqueous saturated Na2CO3 and brine, dried over anhydrous NA2SO4 and concentrated. The product is purified by chromatography on silica (eluent : ETOAC/ HEXANE - 2/3 # ETOAC) to afford 7-methoxy-2,3, 4,5-tetrahydro-2- BENZAZEPIN-1-ONE : API-MS 192 [M+1]+.
		1 1,3,4,5-Tetrahydro-2H-2-benzazepine-2-carbothioamides and 1,2,4,5-tetrahydro-3H-3-benzazepine-3-carbothioamides of the invention were synthesized starting from commercially available 1- or 2-tetralones. The tetralones were converted to the corresponding benzazepinones via a Schmidt reaction. Benzazepinones were then reduced to the corresponding benzazepines with borane. In some cases, the aromatic ring of benzazepines was chlorinated using sulfuryl chloride. The methoxyarylethers were cleaved under reflux in concentrated hydrobromic acid. The protonated benzazepines were coupled to isothiocyanates, which were synthesized from the corresponding amines by reaction with thiophosgene, to give 1,3,4,5-tetrahydro-2H-2-benzazepine-2-carbothioamides or 1,2,4,5-tetrahydro-3H-3-benzazepine-3-carbothioamides. The reaction paths are illustrated in Reaction Schemes A and B.

Reference： [1]Shinde, Anil Karbhari; Badange, Rajesh Kumar; Reballi, Veena; Achanta, Pramod Kumar; Bojja, Kumar; Manchineella, Sravanthi; Rao Muddana, Nageswara; Subramanian, Ramkumar; Choudary Palacharla, Raghava; Benade, Vijay; Jayarajan, Pradeep; Thentu, Jagadeesh Babu; Lingavarapu, Bujji Babu; Yarra, Sivasekhar; Kagita, Narendra; Rao Doguparthi, Mallikarjuna; Mohammed, Abdul Rasheed; Nirogi, Ramakrishna [ChemMedChem, 2022, vol. 17, # 3]
[2]Ortega, Raquel; Hübner, Harald; Gmeiner, Peter; Masaguer, Christian F. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 9, p. 2670 - 2674]
[3]Takeuchi, Kumiko; Holloway, William G.; Mitch, Charles H.; Quimby, Steven J.; McKinzie, Jamie H.; Suter, Todd M.; Statnick, Michael A.; Surface, Peggy L.; Emmerson, Paul J.; Thomas, Elizabeth M.; Siegel, Miles G. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 24, p. 6841 - 6846]
[4]Jesudason, Cynthia D.; Beavers, Lisa S.; Cramer, Jeffrey W.; Dill, Joelle; Finley, Don R.; Lindsley, Craig W.; Stevens, F. Craig; Gadski, Robert A.; Oldham, Samuel W.; Pickard, R. Todd; Siedem, Christopher S.; Sindelar, Dana K.; Singh, Ajay; Watson, Brian M.; Hipskind, Philip A. [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3415 - 3418]
[5]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2004/65351, 2004, A1 Location in patent: Page 112-113
[6]Current Patent Assignee: RESPIRATORIUS - US2005/165004, 2005, A1 Location in patent: Page/Page column 6-7

46
[ 1078-19-9 ]
[ 26231-23-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-Bromosuccinimide; sulfuric acid In water at 70℃; Inert atmosphere;
81%	With N-Bromosuccinimide; sulfuric acid In water at 60℃; for 5h;
61%	With N-Bromosuccinimide; sulfuric acid In water at 60℃; for 5h;

54%	With hydrogen bromide; dihydrogen peroxide; acetic acid In water at 20℃;
	With N-Bromosuccinimide; sulfuric acid In water at 60℃; for 5h;
	With N-Bromosuccinimide In water at 20℃; Darkness;

Reference： [1]Li, Shuangjiang; Wang, Kung K. [Journal of Organic Chemistry, 2019, vol. 84, # 16, p. 10554 - 10558]
[2]Maguire, Casey J.; Chen, Zhi; Mocharla, Vani P.; Sriram, Madhavi; Strecker, Tracy E.; Hamel, Ernest; Zhou, Heling; Lopez, Ramona; Wang, Yifan; Mason, Ralph P.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [MedChemComm, 2018, vol. 9, # 10, p. 1649 - 1662]
[3]He, Yong; Li, Wangyang; Mao, Yanfei; Song, Qiuling; Wang, Hao; Xu, Jie; Yang, Kai [Journal of the American Chemical Society, 2021, vol. 143, # 27, p. 10048 - 10053]
[4]Kobayashi, Susumu; Koyama, Takeshi; Nakanishi, Kenta; Suzuki, Takahiro; Tanino, Keiji [Journal of Organic Chemistry, 2020, vol. 85, # 15, p. 10125 - 10135]
[5]Pravst, Igor; Zupan, Marko; Stavber, Stojan [Tetrahedron Letters, 2006, vol. 47, # 27, p. 4707 - 4710]
[6]Location in patent: experimental part Podgoršek, Ajda; Stavber, Stojan; Zupan, Marko; Iskra, Jernej [Tetrahedron, 2009, vol. 65, # 22, p. 4429 - 4439]

47
[ 1147550-11-5 ]
[ 1078-19-9 ]
6-methoxy-2-thiocyanato-3,4-dihydro-2<i>H</i>-naphthalen-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-Bromosuccinimide In acetonitrile at 20℃; for 7h;	General procedure: Method A: To a stirred solution of ammonium thiocyanate (1 mmol, 0.076 g) and NBS (1 mmol, 0.178 g) in acetonitrile (10 mL) was added acetophenone (1 mmol, 0.12 g) at 0 °C and the resulting mixture was stirred at room temperature for the appropriate time (Table 1). After complete conversion as indicated by TLC, the reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2 × 10 mL). The combined extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting product was purified by column chromatography on silica gel (Merck, 60-120 mesh, ethyl acetate/hexane, 2:8) to afford the pure thiocyanatoketone derivative.
82%	With dipotassium peroxodisulfate; copper(II) sulfate In water; acetonitrile at 60 - 70℃; for 1h;
80%	With phosphomolybdic acid; copper dichloride In 1,2-dichloro-ethane at 20℃; for 0.666667h;

Reference： [1]Location in patent: experimental part Reddy, B.V. Subba; Reddy, S. Madhu Sudana; Madan, Ch. [Tetrahedron Letters, 2011, vol. 52, # 13, p. 1432 - 1435]
[2]Kumar, Atul; Ahamd; Maurya [Tetrahedron Letters, 2007, vol. 48, # 8, p. 1399 - 1401]
[3]Location in patent: experimental part Chaskar, Atul C.; Yadav, Arun A.; Langi, Bhushan P.; Murugappan, Anita; Shah, Chetan [Synthetic Communications, 2010, vol. 40, # 19, p. 2850 - 2856]

48
[ 118994-84-6 ]
[ 1078-19-9 ]
[ 936331-84-9 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 1875 - 1878

49
[ 1078-19-9 ]
[ 144464-66-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 88 percent / aq. HBr 2: 100 percent / Et₃N / CH₂Cl₂ 3: 65 percent / Pd(OAc)2; dppp / dimethylformamide / 65 °C
	Multi-step reaction with 3 steps 1: hydrogen bromide / 48 h / Reflux 2: pyridine / 0 - 20 °C 3: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 48 h / 120 °C / 22502.3 Torr / Sealed tube
	Multi-step reaction with 3 steps 1: hydrogen bromide / water / 24 h / 100 °C 2: triethylamine / dichloromethane / 2 h / 20 °C 3: N-ethyl-N,N-diisopropylamine; palladium diacetate; 1,3-bis-(diphenylphosphino)propane / N,N-dimethyl-formamide / 22 h / 65 °C

Reference： [1]Fotsch, Christopher; Biddlecome, Gloria; Biswas, Kaustav; Chen, Jian Jeff; D'Amico, Derin C.; Groneberg, Robert D.; Han, Nianhe Bruce; Hsieh, Feng-Yin; Kamassah, Augustus; Kumar, Gondi; Lester-Zeiner, Dianna; Liu, Qingyian; Mareska, David A.; Riahi, Babak Bobby; Wang, Yueh-Ju Judy; Yang, Kevin; Zhan, James; Zhu, Joe; Johnson, Eileen; Ng, Gordon; Askew, Benny C. [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 8, p. 2071 - 2075]
[2]Current Patent Assignee: MERCK & CO INC - WO2014/74422, 2014, A1
[3]Zhou, Zijun; Wang, Yang; Li, Jun; Hu, Baichun; Lin, Xiaolin; Chen, Ye; Wang, Rui; Liu, Ju; Liu, Hongsheng [Medicinal Chemistry Research, 2018, vol. 27, # 8, p. 1863 - 1875]

50
[ 1078-19-9 ]
[ 32263-70-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 99 - 102
[2]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2758 - 2763

51
[ 1078-19-9 ]
[ 1769-84-2 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1997,p. 1511 - 1516

52
[ 1078-19-9 ]
/PMAMJ₁₆₂--930/ [ No CAS ]
[ 1769-84-2 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 1704 - 1719

53
[ 1078-19-9 ]
/PMAMJ₁₆₂--930/ [ No CAS ]
[ 87901-81-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1994,vol. 31,p. 1251 - 1258

54
[ 1078-19-9 ]
[ 51015-29-3 ]

Reference： [1]Synthetic Communications,1993,vol. 23,p. 2965 - 2971

55
[ 1078-19-9 ]
[ 90401-84-6 ]

Reference： [1]Synthetic Communications,1993,vol. 23,p. 2965 - 2971

56
[ 1078-19-9 ]
[ 80858-95-3 ]

Reference： [1]Synthetic Communications,1982,vol. 12,p. 763 - 770
[2]Journal of the Chemical Society. Chemical communications,1990,p. 518 - 519
[3]Patent: WO2017/123518,2017,A1

57
[ 1078-19-9 ]
[ 2472-22-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: NaBH₄ / methanol / 4 h / Ambient temperature 2: 93 percent / oxalic acid / H₂O / 6 h / Heating 3: 1.) formic acid, 30 percent hydrogen peroxide; 2.) 20 percent H₂SO₄ / 1.) 35 deg C, 2 h, room temp., 12 h; 2.) reflux, 10 h
	Multi-step reaction with 3 steps 1: 1.) sodium borohydride, ethanol, 15 min., reflux 2.) p-toluenesulfonic acid, benzene, reflux 2: 76 percent / N-methylmorpholine N-oxide, osmium tetroxide / H₂O; acetone; 2-methyl-propan-2-ol; CCl₄ / overnight 3: 98 percent / p-toluenesulfonic acid / benzene / 0.25 h / Heating
	Multi-step reaction with 3 steps 1: caesium carbonate / toluene; 1,4-dioxane 2: dichloro(1,5-cyclooctadiene)palladium(II); caesium carbonate; C11H15NO; 2′-(diphenylphosphino)-N,N′-dimethyl-(1,1′-biphenyl)-2-amine; 5-(trifluoromethyl)-2(1H)-pyridone / toluene / 24 h / 100 °C 3: water / toluene / Acidic conditions

Reference： [1]Vebrel, Joel; Carrie, Robert [Bulletin de la Societe Chimique de France, 1982, vol. 2, # 5-6, p. 161 - 166]
[2]Hauser, Frank M.; Prasanna, Subbarao [Synthesis, 1980, # 8, p. 621 - 623]
[3]Wu, Zhao; Xu, Xiaolong; Wang, Jianchun; Dong, Guangbin [Science, 2021, vol. 374, # 6568, p. 734 - 740]

58
[ 1078-19-9 ]
[ 116854-10-5 ]

Reference： [1]Synthesis,1987,p. 845 - 846

59
[ 1078-19-9 ]
[ 27752-24-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1984,p. 5 - 13
[2]Journal of Organic Chemistry,2015,vol. 80,p. 4722 - 4728

60
[ 7252-82-6 ]
[ 1078-19-9 ]

Reference： [1]Tetrahedron,1987,vol. 43,p. 1847 - 1856
[2]Tetrahedron Letters,1987,vol. 28,p. 4163 - 4164

61
[ 6943-97-1 ]
[ 1078-19-9 ]

Reference： [1]Australian Journal of Chemistry,1990,vol. 43,p. 815 - 824
[2]Australian Journal of Chemistry,1990,vol. 43,p. 815 - 824

62
[ 1078-19-9 ]
[ 15159-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: HCl, ZnCl₂, AcOH 2: ethanol / Heating 3: Raney-Ni / ethanol / Heating

Reference： [1]Delobelle,J.; Fetizon,M. [Bulletin de la Societe Chimique de France, 1961, p. 1900 - 1905]

63
[ 108-86-1 ]
[ 1078-19-9 ]
[ 1769-84-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium t-butanolate;dichloro bis((p-dimethylaminophenyl)-?-di-tert-butylphosphine)palladium(II); In toluene; at 60℃; for 18h;Inert atmosphere;Product distribution / selectivity;	Scheme 2 ynthesis of 6-methoxy-2-phenyl-3,4-dihvdronaphthalene-1 (2H)-oneA)91 % crude yield98% HPLC purity6-Methoxy-3,4-dihydronaphthalene-1 (2H)-one (I, 352 mg, 2.0 mmol), NaOf-Bu (365 mg, 3.8 mmol) and Pd-132 (14 mg, 0.02 mmol) were added to a Schlenk flask. The flask was sealed with a rubber stopper, evacuated and backfilled with nitrogen three times. Bromobenzene (0.21 mL, 2.0 mmol) followed by toluene (2.0 mL), was added via airtight syringe through the rubber stopper, and the reaction mixture was stirred at 60 C for 18 hours. The reaction mixture was filtered on silica gel and the silica pad was washed with MTBE (20 mL). The filtrate was concentrated to give the desired product as an off-white solid (461 mg, 91 %). H NMR (CDCI3) delta = 2.39 - 2.44 (m, 2H), 3.0 - 3.1 (m, 2H), 3.8 (t, 1 H), 3.9 (s, 3H), 6.7 (d, 1 H), 6.9 (dd, 1 H), 7.2 (m, 2H), 7.3 (m, 1 H), 7.4 (m, 2H), 8.1 (d, 1 H) ppm.3C NMR (CDCI3) delta = 28.9, 31 .2, 54.0, 55.4, 1 12.4, 1 13.2, 1 26.4, 1 26.7, 128.35, 1 28.4, 130.2, 140.0, 146.5, 1 63.5, 1 96.9 ppm.
91%	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium t-butanolate; In toluene; at 60℃; for 18h;Schlenk technique; Inert atmosphere;	4.2.1.1. From bromobenzene. Tetralone 1 (352 mg, 2.0 mmol), NaOt-Bu (365 mg, 3.8 mmol) and Pd-132 (14 mg, 0.02 mmol) wereadded to a Schlenk flask. The flask was sealed with a rubber stopper,evacuated and backfilled with nitrogen three times. Bromobenzene(0.21 mL, 2.0 mmol) followed by toluene (2.0 mL),was added via airtight syringe through the rubber stopper, andthe reaction mixture was stirred at 60 C for 18 h. The reactionmixture was filtered through silica gel and the silica pad waswashed with MTBE (20 mL). The filtrate was concentrated to givethe desired product 2 as an off-white solid (461 mg, 91%).
33%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 5,5-dimethyl-1,3-cyclohexadiene; at 130℃; for 24h;Sealed tube;	A mixture of 6-methoxy-3,4-dihydronaphthalen-l(2H)-one LI 8-1 (20 g, 120.5 mmol), benzyl bromide (22.7 g, 144.5 mmol) and cesium carbonate (117 g, 359.1 mmol) in xylene (200 mL) was degassed with argon for 15 min in a seal tube at room temperature. To the resulting solution was added Pd(OAc)2(1.34 g, 5.982 mmol) and Xanthphos (3.5 g, 6.055 mmol) and degassing was continued for another 15 min. The reaction mixture was sealed properly and heated to l30C for 24 h. After completion of the reaction (monitored by TLC and LCMS), the reaction mixture was diluted with water and extracted with ethyl acetate (3 x ). The combined organic layer was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The resulting crude compound was purified by silica gel column chromatography eluting with 0-10% ethyl acetate in -hexane to afford 10 g (33% yield) of compound L18-2 as off white solid.LCMS-Condition 01: [M + H]+= 253.05; Rt = 1.95 min NMR (400 MHz, DMSO-r/e) d: 7.87 (d, J= 9.29 Hz, 1H), 7.29-7.34 (m, 2H), 7.22-7.26 (m, 1H), 7.17 (d, J = 7.34 Hz, 2H), 6.89-6.95 (m, 2H), 3.88 (d, = 4.89 Hz, 1H), 3.85 (s, 3H), 3.06-3.16 (m, 1H), 2.95 (td, J= 4.04, 16.87 Hz, 1H), 2.21-2.39 (m, 2H).

	With potassium tert-butylate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl;palladium diacetate; In toluene; at 100℃; for 2.16667h;	A mixture OF PALLADIUM (IN acetate (0.57 g), rac-2,2'-bis (diphenylphosphino) - 1, L'-BINAPHTYL (1.91 g) and potassium tert-butoxide (4.15 g) in dry toluene was stirred under argon for 10 minutes. Bromobenzene (5.34 g) and 6-methoxy-1-tetralo- ne (3.0 g) solvated in dry toluene were added and the mixture was stirred at 100 C for 2 h. The reaction mixture was cooled to room temperature and poured into saturated aqueous ammonium chloride and extracted with ethyl ether. Organic extract was washed with brine, dried and evaporated. The crude product was purified by flash chromatography on silica gel using toluene and toluene-ethyl acetate (9: 1) as an ELUANT. 1H NMR (400 MHz, d6-DMSO) 6 : 7.87 (d, 1H, J 7.8 Hz), 7.16-7. 33 (m, 5H), 6.91-6. 94 (m, 2H), 3.85 (s, 3H), 3.82-3. 88 (m, 1H), 3.06-3. 14 (m, 1H), 2.92-2. 98 (m, 1H), 2.23-2. 38 (m, 2H).
	With sodium t-butanolate;di-tert-butyl[dichloro({di-tert-butyl[4-(dimethylamino)phenyl]phosphaniumyl})palladio][4-(dimethylamino)phenyl]phosphanium; In toluene; at 60℃; for 18h;Sealed flask; Inert atmosphere;Product distribution / selectivity;	6-Methoxy-3,4-dihydronaphthalene-1(2H)-one (1, 352 mg, 2.0 mmol), NaOt-Bu (365 mg, 3.8 mmol) and Pd-132 (14 mg, 0.02 mmol) were added to a Schlenk flask. The flask was sealed with a rubber stopper, evacuated and backfilled with nitrogen three times. Bromobenzene (0.21 mL, 2.0 mmol) followed by toluene (2.0 mL), was added via airtight syringe through the rubber stopper, and the reaction mixture was stirred at 60C for 18 hours. The reaction mixture was filtered on silica gel and the silica pad was washed with MTBE (20 mL). The filtrate was concentrated to give the desired product as an off-white solid (461 mg, 91 %). 1H NMR (CDCl3) delta = 2.39 - 2.44 (m, 2H), 3.0 - 3.1 (m, 2H), 3.8 (t, 1 H), 3.9 (s, 3H), 6.7 (d, 1 H), 6.9 (dd, 1H), 7.2 (m, 2H), 7.3 (m, 1 H), 7.4 (m, 2H), 8.1 (d, 1 H) ppm. 13C NMR (CDCl3) delta = 28.9, 31.2, 54.0, 55.4, 112.4, 113.2, 126.4, 126.7, 128.35, 128.4, 130.2, 140.0, 146.5, 163.5, 196.9 ppm.
	With sodium t-butanolate; In toluene; at 60℃; for 18h;Schlenk technique; Inert atmosphere;	6- Methoxy- 3, 4- dihydronaphthalene- 1 (2H)- one (l, 352 mg, 2.0 mmol), NaOt- Bu (365 mg, 3.8 mmol) and Pd- 132(14 mg, 0.02 mmol) were added to a Schlenk flask. The flask was sealed with a rubber stopper, evacuated and backfilledwith nitrogen three times. Bromobenzene (0.21 mL, 2.0 mmol) followed by toluene (2.0 mL), was added via airtightsyringe through the rubber stopper, and the reaction mixture was stirred at 60 C for 18 hours. The reaction mixture wasfiltered on silica gel and the silica pad was washed with MTBE (20 mL) . The filtrate was concentrated to give the desiredproduct as an off- white solid (461 mg, 91 %) .1H NMR (CDCl3) f = 2.39- 2.44 (m, 2H), 3.0- 3.1 (m, 2H), 3.8 (t, 1 H), 3.9 (s, 3H), 6.7 (d, 1H), 6.9 (dd, 1H), 7.2 (m, 2H),7.3 (m, 1H), 7.4 (m, 2H), 8.1 (d, 1H) ppm.13C NMR (CDCl3) f = 28.9, 31.2, 54.0, 55.4, 112.4, 113.2, 126.4, 126.7, 128.35, 128.4, 130.2, 140.0, 146.5, 163.5, 196.9ppm.
	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium t-butanolate; In toluene; at 80℃; for 16h;	4-((1R,2S)-6-Methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenol 101d was prepared according to Lednicer D., et al (1969) J. Med. Chem. 12:881-885 by alpha-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one 101a with phenyl bromide and palladium catalysis to give 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one 101b. Formation of the enol triflate of 101b with triflic anhydride followed by coupling with (4-hydroxyphenyl)boronic acid gave 4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenol 101c. Hydrogen reduction of 101c with palladium on carbon gave the cis 101d, also known as 4-(cis-6-methoxy-2-phenyl-tetralin-1-yl)phenol.

Reference： [1]Patent: WO2012/159981,2012,A2 .Location in patent: Page/Page column 19-20
[2]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 2691 - 2697
[3]Patent: WO2019/144132,2019,A1 .Location in patent: Paragraph 000258; 000425
[4]Patent: WO2004/63191,2004,A1 .Location in patent: Page 40-41
[5]Patent: JP2005/504738,2005,A .Location in patent: Page/Page column 39-40
[6]Patent: EP2524908,2012,A1 .Location in patent: Page/Page column 13
[7]Patent: EP2644603,2013,A1 .Location in patent: Paragraph 0082
[8]Patent: US2017/129855,2017,A1 .Location in patent: Paragraph 0182
[9]Patent: WO2020/55973,2020,A1 .Location in patent: Paragraph 0024; 0088-0090

64
[ 1073-06-9 ]
[ 1078-19-9 ]
[ 861930-31-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 115℃; for 18h;	2 Charge an oven-dried 250 mL round-bottom flask with 6-methoxy-1-tetralone (3. 0g, 17.0 mmol. ) and place under nitrogen. Dissolve the solid in toluene (30mL) and add 1-bromo-3-fluorobenzene (4. 7 mL, 42.6 mmol), sodium t-butoxide (6.5g, 68.1 mmol), palladium acetate (76mg, 0.34 mmol), and racemic BINAP (212mg, 0.34 mmol). Heat the solution to 115°C and stir for 18 hours. Dilute the solution with cold 5N HC1 (50mL) and ethyl acetate (200mL). Separate the organic layer and dry over sodium sulfate, filter over a pad of celite and concentrate in vacuo. Purify the crude product using radial chromatography to give 3.4 g (74%) of the title compound. This material is used without further purification: mass spectrum (ion spray) m/z =267 (M-H). Dissolve 2- (3-fluoro-phenyl)-6-methoxy-naphthalen-l-ol (3.36g, 12.5 mmol) in N-methyl-2-pyrrolidinone (NMP) (lOmL) and add sodium hydride (500mg, 60% oil dispersion, 12.5 mmol) at room temperature. After stirring for 1 hour this solution is added to a solution of 4-fluorobenzaldehyde (2.4mL, 22.5 mmol) in NMP (lOmL) that has been heated to 185°C. Continue stirring for 2.5 hours. Cool the reaction to room temperature and add pH 7 buffer (50mL) and extract with ethyl acetate (2 X 100mL). Wash the organic extracts with water and filter through a plug of silica gel. Purify the crude product using radial chromatography giving 2. 50g (54%) of the title compound and use without further purification: mass spectrum (ion spray) m/z = 371 (M-H). Charge a 100 mL round-bottom flask with 4- [2- (3-fluoro-phenyl)-6-methoxy- naphthalen-l-yloxy]-benzaldehyde (2. 5g, 6.71 mmol) and ethyl acetate (5 mL). At room temperature add 2 mL of 35% hydrogen peroxide. To this solution slowly add 2 mL of concentrated sulfuric acid. The mixture warms to approximately 40 °C and returns to room temperature where it is stirred for 2 hours. Dilute the reaction with water and ethyl acetate (100 mL) and dry the organic layer over sodium sulfate, filter and concentrate in vacuo. Purify the crude product using radial chromatography eluting with CH2C12 to yield 540 mg (22%) of the title compound: mass spectrum (ion spray) m/z = 359 (M-H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO; PFIZER INC - WO2005/73204, 2005, A1 Location in patent: Page/Page column 21-22

65
[ 3466-32-8 ]
[ 1078-19-9 ]
[ 648906-33-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: 4-bromoohenyl methyl sulfone; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In toluene Heating / reflux; Stage #2: With sodium t-butanolate In toluene at 20 - 80℃; for 1 - 2h; Stage #3: With water In toluene at 40℃;	32 Add 6-methoxytetralone (1.0 eq. ), 4-bromophenyl-methyl-sulfone (1.02 eq. ), Pd (OAc) 2 (0.025 eq. ), DPEphos ligand [(Oxydi-2, 1-phenylene) bis (diphenylphosphine)] (0.026 eq. ) and toluene (12 vols) to a three-neck flask equipped with a reflux condenser and nitrogen vent purge. Then add sodium t-butoxide (2.5 eq. ) in one portion. The reaction mixture exotherms to approximately 40°C and forms a heterogeneous yellow mixture. Heat the heterogeneous yellow reaction mixture to 75°-80°C for 1-2 hours. Cool the yellow slurry to room temperature and slowly quench the reaction with water (12 vols), keeping the temperature below 40°C. Cool the aqueous slurry to room temperature and stir for 2 to 3 hours. Filter the slurry over polypropylene and wash the solids with water (3x2 vols). Dry the resulting filter cake in a vacuum overnight at 50° C to provide crude 2- (4-methanesulfonyl-phenyl)-6-methoxy-3, 4-diliydro-2H-naphthalen-1-one (91%). Add 2- (4-methanesulfonyl-phenyl)-6-methoxy-3, 4-dihydro-2H-naphthalen-1-one (1. 0 eq.), hyflo (20 wt%), and toluene (7.5 vols) to a three neck flask with a reflux condenser and nitrogen vent purge. While stirring at room temperature, add PBr3 (1. 75 eq. ) in one portion. Heat the reaction to reflux (-110° C) overnight allowing it to vent through a caustic scrubber. After refluxing for 15 hours, cool the yellow solution to 45°C and slowly add THF (20 vols). Stir this mixture for 30 minutes at 45'and filter it, while warm, over a pad of Hyflo. Wash the pad with 45°C THF (2X2 vols). Concentrate the filtrate at reduced pressure to remove all of the THF. Carefully add water (7.5 vols) to the remaining mixture keeping the temperature below 40°C. Cool the slurry to room temperature and stir it for 2 to 3 hours. Filter the slurry over a polypropylene pad and wash it with water (2x2 vols). Dry the resulting filter cake in a vacuum oven overnight at 50°C to provide the title compound (74%).
	Stage #1: 4-bromoohenyl methyl sulfone; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In toluene Heating / reflux; Stage #2: With sodium t-butanolate In toluene at 40 - 80℃;	33 To a 3-neck flask equipped with a reflux condenser and nitrogen vent purge, add 6-methoxytetralone (1. 0 eq. ), 4-bromophenyl-methyl-sulfone (1. 02-1. 05 eq. ), Pd (OAc) 2 (0.025 eq. ), DPEphos ligand (0.026 eq. ) and toluene 10-12 volumes. Add sodium t- butoxide (2.5 eq. ) in one portion and allow mixture to exotherm to-40°C. Heat to 75° to 80° C. Upon the reaction completion, as judged by HPLC analysis, cool to room temperature. Add 12 volumes water slowly keeping the temperature <40°C. Stir 2 to 3 hours. Filter over polypropylene pad and wash with water (3 x 2 volumes). Dry the filter cake overnight at 50° C to give 2- (4-methanesulfonylphenyl)-6-methoxytetralone. Combine 2- (4-methanesulfonylphenyl)-6-methoxytetralone (1.0 eq. ), hyflo (20%/weight), and toluene (7.5 volumes). Add PBr3 (1. 5-1. 75 eq. ) in one portion while stirring at room temperature. Heat contents to reflux (-110° C) overnight. Upon reaction completion, as judged by HPLC analysis (usually 15 hours), cool solution to 45°C and slowly add 20 volumes THF. Stir for 30 minutes at 45° and filter warm over a pad of hyflo. The pad is washed with 2x2 volumes THF at 45° C. Concentrate filtrate to approximately 7 volumes. Add 7.5 volumes water to the remaining mixture keeping the temperature below 40° C. (NOTE: initial addition of water is very exothermic with large evolution of HBr). Cool slurry to room temperature and stir for 2 to 3 hours. Filter over a polypropylene pad and wash with 2 x 2 volumes water. Dry filter cake overnight at 60°C under vacuum to give l-bromo-2- (4-methanesulfonylphenyl)-3, 4-dihydro-6- methoxynaphthalene. Combine l-bromo-2-(4-methanesulfonylphenyl)-3, 4-dihydro-6- methoxynaphthalene and 2,3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ, 1.8 equiv.) in 10 volumes acetonitrile and 5 volumes of THF. Under nitrogen atmosphere, heat reaction contents to 73-75°C. Monitor reaction progress by GC analysis until reaction completion. Additional DDQ (0.2-0. 3 equiv.) may be required for reaction completion. Cool contents to ambient temperature and add 10 volumes 1 N sodium hydroxide. Stir for approximately 1 hour and filter. Rinse filter cake with 2 volumes water, 3x5 volumes 50% acetonitrile/water and finally 3 volumes methanol. Vacuum dry the filter cake at 65°C to give the title compound.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2004/9086, 2004, A1 Location in patent: Page/Page column 92-93
[2]Current Patent Assignee: ELI LILLY & CO - WO2004/9086, 2004, A1 Location in patent: Page/Page column 94-95

66
[ 104-95-0 ]
[ 1078-19-9 ]
[ 648905-51-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (4-bromophenyl)thioanisole; 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In toluene Heating / reflux; Stage #2: With sodium t-butanolate In toluene at 20℃; for 2 - 4h; Heating / reflux; Stage #3: With hydrogenchloride In tetrahydrofuran; water; toluene at 20℃; for 0.5h;	28 Place 6-methoxy-1-tetralone (1 eq. ), 4-bromothioanisole (2.5 eq. ), palladium acetate (0.01 eq.), 2-dicyclohexylphosphino-2'- (N, N-dimethylamino) biphenyl (0.02 eq. ) and toluene in a 3 neck flask equipped with a mechanical stirrer, reflux condenser, nitrogen purge and a temperature probe. Add sodium tert-butoxide (4 eq. ) and heat the slurry to reflux. After about 2-4 hours, cool the reaction to room temperature and add 3M aqueous HC1 along with tetrahydrofuran. Stir the biphasic reaction mixture for 30 minutes before filtration and separation of the layers. Concentrate the organic layer to isolate 6-methoxy-2-(4-methylthiophenyl) naphthalene-1-ol by filtration. Place sodium hydride (1.05 eq. ) in dry dimethylformamide in a 3 neck flask equipped with a mechanical stirrer, addition funnel with nitrogen purge, and a temperature probe under nitrogen. Charge the addition funnel with 6-methoxy-2- (4- methylthiophenyl) naphthalene-l-ol (1 eq. ) dissolved in dry dimethylformamide. Add this solution dropwise to the stirred sodium hydride solution at a rate that holds the temperature below 35°C. Stir the reaction mixture for 30 minutes before adding 4-fluoronitrobenzene with additional dry dimethylformamide. Heat the solution to 60°C. Once the reaction is complete, cool the flask and add water slowly to cause precipitation of the product. Filter the crude product and wash with water and then methyl tert-butyl ether. Dry the filter cake in a vacuum oven to give 6-methoxy-2- (4-methylthiophenyl)-1- (4-nitrophenoxy) naphthalene. Place meta-chloroperbenzoic acid (2. 5 eq. ) and methylene chloride in a 3 neck flask equipped with a mechanical stirrer, addition funnel with nitrogen purge, and a temperature probe. Charge the addition funnel with 6-methoxy-2- (4-methylthiophenyl)-1- (4-nitrophenoxy) naphthalene (1 eq. ) dissolved in methylene chloride. Add this solution dropwise to the stirred slurry of perbenzoic acid at 10°C. Upon completion of the addition, stir the solution for 30 minutes. Upon reaction completion, add 1N aqueous NaOH slowly holding the temperature at or below 25°C."Separate the layers and concentrate the organic layer. Purify the crude reaction concentrate on silica gel eluting with methylene chloride to afford 6-methoxy-2-(4-methanesulfonylphellyl)-1-(4- nitrophenoxy) naphthalene. Place 6-methoxy-2-(4-methanesulfonylphenyl)-1-t4-nitrophenoxy) naphthalene in a hydrogenation vessel with 3 volumes of dimethylformamide and 5% Pd/C catalyst. Pressurize the vessel with hydrogen and once the reaction is deemed complete, remove the catalyst by filtering over Hyflo. To the filtrate add IN aqueous HC1 to precipitate the crude product. Filter the precipitate, wash with IN aqueous HCl and place the filter cake in a vacuum drying oven to give 6-metlioxy-2- (4-methanesulfonylphenyl)-1- (4- aminophenoxy) naphthalene hydrochloride. Place 6-methoxy-2-(4-methanesulfonylphenyl)-1-(4-aminophenoxy) nsaphthalene hydrochloride (1 eq. ), iodine (0.6 eq. ), copper iodide (1. 05 eq. ) and acetonitrile in a 3 neck flask equipped with a mechanical stirrer, addition funnel, nitrogen purge and temperature probe. Charge the addition funnel with isoamylnitrite (1. 1 eq. ) in acetonitrile and add this mixture dropwise at 20°C or below. After the addition, stir the mixture for 1 hour. Once the reaction is complete, add saturated sodium thiosulfate and methylene chloride to the mixture and stir for 1 hour. Filter the reaction mixture and separate the layers. Concentrate the organic layer to form a solid. Purify the solid on silica gel to afford the title compound.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2004/9086, 2004, A1 Location in patent: Page/Page column 85-86

67
[ 120-14-9 ]
[ 1078-19-9 ]
[ 149862-20-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide In ethanol; water	7 2-(3,4-Dimethoxybenzylidene)-6-methoxy-1-tetralone 2-(3,4-Dimethoxybenzylidene)-6-methoxy-1-tetralone 6-Methoxy-1-tetralone (7.04 g, 40 mmol) and 3,4-dimethoxybenzaldehyde (6.44 g, 40 mmol) are mixed with 100 ml of absolute ethanol. The mixture is stirred for 0.5 h to dissolve as much as possible of the reagents. The introduction of gaseous hydrogen chloride is commenced. An exothermic reaction is noted which enables the complete dissolution of all of the reagents. The round-bottomed flask is cooled from time to time with an ice bath so that the temperature does not exceed 80° C. The mixture is thus saturated with hydrogen chloride after 1 h to give an intense red color. This mixture is allowed to stand at room temperature for 2 h. The reaction mixture is poured into a mixture of 400 ml of water and 40 ml of aqueous NaOH (3N). It is stirred vigorously for 3 h at room temperature. The precipitated solid is filtered over a glass frit, washed with water and finally dried under vacuum, over P2 O5, to give a solid (12.35 g, 95%). A small quantity of product is recrystallized from the mixture AcOEt/hexane=1:2.
86%	With potassium hydroxide In methanol at 5 - 20℃;
75%	With sodium hydroxide In ethanol at 20℃; for 12h;	4.1.5. General procedure for the synthesis of 6-methoxy-2-(arylidene)-3,4-dihydronaphthalen-1(2H)-ones 9a-c General procedure: A mixture of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1)(1.76 g, 10 mmol), the appropriate aldehyde 8a-c (10 mmol) and 10% sodium hydroxide solution (10%, 15 mL) in ethanol (30 mL) was stirred for 12 h at room temperature. The separated precipitate was filtered,washed with water and crystallized from ethanol to yield compounds 9a-c, respectively.

Reference： [1]Current Patent Assignee: OXIS INTERNATIONAL INC - US5543298, 1996, A
[2]Gautam, Yashveer; Dwivedi, Sonam; Srivastava, Ankita; Hamidullah; Singh, Arjun; Chanda; Singh, Jyotsna; Rai, Smita; Konwar, Rituraj; Negi, Arvind S. [RSC Advances, 2016, vol. 6, # 40, p. 33369 - 33379]
[3]Abdelsalam, Esraa A.; Zaghary, Wafaa A.; Amin, Kamilia M.; Abou Taleb, Nageh A.; Mekawey, Amal A.I.; Eldehna, Wagdy M.; Abdel-Aziz, Hatem A.; Hammad, Sherif F. [Bioorganic Chemistry, 2019, vol. 89]

68
bromhydric acid [ No CAS ]
[ 1078-19-9 ]
[ 3470-50-6 ]

Yield	Reaction Conditions	Operation in experiment
84.7%	In acetic acid;	The starting material was prepared as follows: A mixture of 6-methoxy-1-tetralone (5 g, 28.4 mmol) in acetic acid (50 ml) and 48% bromhydric acid (25 ml) was heated at reflux for 7 hours. After extraction with CH2 Cl2 and evaporation, the residue was purified by flash chromatography (AcoEt/petroleum ether 45/55) to give 6-hydroxy-1-tetralone as a foam (3.9 g; 84.7%). 1 H-NMR (DMSO-d6) δ: 1.95-2 (m, 2H); 2.46-2.52 (m, 2H); 2.83 (t, 2H); 6.64 (d, 1H); 6.70 (dd, 1H); 7.73 (d, 1H).
84.7%	In acetic acid;	The starting material was prepared as follows: A mixture of 6-methoxy-1-tetralone (5 g, 28.4 mmol) in acetic acid (50 ml) and 48% bromhydric acid (25 ml) was heated at reflux for 7 hours. After extraction with CH2Cl2 and evaporation, the residue was purified by flash chromatography (AcoEt/petroleum ether 45/55) to give 6-hydroxy-1-tetralone as a foam (3.9 g; 84.7%). 1H-NMR (DMSO-d6) δ: 1.95-2 (m, 2H); 2.46-2.52 (m, 2H); 2.83 (t, 2H); 6.64 (d, 1H); 6.70 (dd, 1H); 7.73 (d, 1H).

Reference： [1]Patent: US5607928,1997,A
[2]Patent: EP695753,1996,A1

69
[ 51145-58-5 ]
[ 1078-19-9 ]
5-methoxy-1-tetralone-(4-benzyloxyphenyl)-hydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	acetic acid; In ethanol; for 1h;Heating / reflux;	5-Methoxy-1-tetralone-(4-Benzyloxyphenyl)-hydrazone A solution of 6-methoxy-1-tetralone [1078-19-9]* (14.8 g, 84 mmol) and 4-benzyloxyphenyl hydrazine [5111-70-6]** (15.0 g, 70 mmol) and a few drops of AcOH in EtOH was heated to reflux for 1 hr. The reaction was then cooled and a solid precipitated out. The solid was filtered to give 21.5 g of #14: Mp = 86 - 91C; 1H NMR (DMSO) 8.8 (s, 1 H), 8.00 - 6.50 (m, 12 H), 5.00 (s, 2 H), 3.82 (s, 3 H), 2.80 - 2.65 (m, 4 H), 1.90 (t, 2 H, J = 6.0 Hz).

Reference： [1]Patent: EP1082319,2006,B1 .Location in patent: Page/Page column 10; 17

70
[ 16420-13-6 ]
[ 74-88-4 ]
[ 1078-19-9 ]
[ 3470-50-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; NaH;AlCl3; In N-methyl-acetamide; methanol; cyclohexane; N,N-dimethyl-formamide; mineral oil;	EXAMPLE 31 6-Thiomethyl1-tetralone 6-Hydroxy- 1-tetralone (16.2 g) prepared from 6-methoxy1-tetralone and AlCl3, was dissolved in dry dimethylformamide (DMF)(50 ml) and added dropwise to a suspension of 4 g NaH (60% in mineral oil) and dry DMF (200 ml) over 30 min. Then, dimethylthiocarbamyl chloride (14.8 g) was added and the reaction heated at 85 C. for, 4 hrs. The reaction was poured onto ice and extracted with CH2 Cl2 (150 ml). The CH2 Cl2 layer was washed with 10% aq. NaOH, then saturated NaCl solution. The organic layer was separated, dried (Na2 SO4), filtered and evaporated giving a tan solid (18.1 g). This was added to mineral oil (100 ml) and heated at 270 C. for 2 hrs, then cooled. Cyclohexane (500 ml) was added and a solid separated (14.3 g). This product was added to NaOH (10 g) and MeOH (150 ml) and refluxed 2 hrs. The reaction was cooled, then methyliodide (9.94 g) was added followed by refluxing for 2 hrs.
	With sodium hydroxide; NaH;AlCl3; In N-methyl-acetamide; methanol; cyclohexane; N,N-dimethyl-formamide; mineral oil;	EXAMPLE 31 6-Thiomethyl-1-tetralone 6-Hydroxy-1-tetralone (16.2 g) prepared from 6-methoxy 1-tetralone and AlCl3, was dissolved in dry dimethylformamide (DMF)(50 ml) and added dropwise to a suspension of 4 g NaH (60% in mineral oil) and dry DMF (200 ml) over 30 min. Then, dimethylthiocarbamyl chloride (14.8 g) was added and the reaction heated at 85 C. for 4 hrs. The reaction was poured onto ice and extracted with CH2 Cl2 (150 ml). The CH2 Cl2 layer was washed with 10% aq. NaOH, then saturated NaCl solution. The organic layer was separated, dried (Na2 SO4), filtered and evaporated giving a tan solid (18.1 g). This was added to mineral oil (100 ml) and heated at 270 C. for 2 hrs, then cooled. Cyclohexane (500 ml) was added and a solid separated (14.3 g). This product was added to NaOH (10 g) and MeOH (150 ml) and refluxed 2 hrs. The reaction was cooled, then methyliodide (9.94 g) was added followed by refluxing for 2 hrs.

Reference： [1]Patent: US5086074,1992,A
[2]Patent: US5128362,1992,A

71
trimethylsilyl cyanide (TMSCN) [ No CAS ]
[ 1078-19-9 ]
[ 6398-50-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With hydrogenchloride In sodium hydroxide; water; ethyl acetate; benzene	1 1-Cyano-6-methoxy-3,4-dihydronaphthalene EXAMPLE 1 1-Cyano-6-methoxy-3,4-dihydronaphthalene To a refluxing benzene solution (60 ml) of 6-methoxy-1-tetralone was added trimethylsilyl cyanide (TMSCN) (67.5 g) and a trace of AlCl3 or ZnI2. Refluxing was continued for 1 hr., then the solvent removed under vacuum. Isopropyl alcohol saturated with HCl(g) was added and the solution refluxed for 1 hr. Precipitation began to occur and the reaction was cooled, then evaporated to dryness. Water was added, followed by an ethyl acetate (EtOAc) extraction. The organic layer was washed in sequence with IN NaOH, 1N HCl, and brine, separated, dried (MgSO4), filtered and evaporated. The dark oil was chromatographed on silica gel and eluted with CH2 Cl2, affording 98.5 g, 94% yield of product.
94%	With hydrogenchloride; sodium hydroxide In water; ethyl acetate; benzene	1 1-Cyano-6-methoxy-3,4-dihydronaphthalene EXAMPLE 1 1-Cyano-6-methoxy-3,4-dihydronaphthalene To a refluxing benzene solution (60ml) of 6-methoxy-1-tetralone was added trimethylsilyl cyanide (TMSCN) (67.5g) and a trace of AlCl3 or ZnI2. Refluxing was continued for 1 hr., then the solvent removed under vacuum. Isopropyl alcohol saturated with HCl(g) was added and the solution refluxed for 1 hr. Precipitation began to occur and the reaction was cooled, then evaporated to dryness. Water was added, followed by an ethyl acetate (EtOAc) extraction. The organic layer was washed in sequence with 1N NaOH, 1N HCl, and brine, separated, dried (MgSO4), filtered and evaporated. The dark oil was chromatographed on silica gel and eluted with CH2 Cl2, affording 98.5g, 94% yield of product.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5086074, 1992, A
[2]Current Patent Assignee: ABBOTT LABORATORIES INC - US5128362, 1992, A

72
[ 616-38-6 ]
[ 1078-19-9 ]
[ 40153-87-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydride Inert atmosphere; Reflux;	4.2. Typical procedure for the synthesis of 2-(methoxycarbonyl)tetralones 5 General procedure: A solution of α-tetralone (10 mmol) in dimethyl carbonate(5 mL) was added to a stirred suspension of NaH (60% dispersion,15 mmol) in dimethyl carbonate (10 mL) under argon atmosphere.The solution was refluxed and once the reaction was judged completeafter a TLC test the solvent was evaporated. The resultant solid was dissolved in hydrochloric acid (2 M) and the phases were separated. The aqueous phase was extracted with ethyl acetate(35 mL). The organic extracts were dried (MgSO4) and evaporated to dryness. Flash chromatography (EtOAc/hexane 10%) afforded the pure products.
98%	With sodium hydride Inert atmosphere; Reflux;	Methyl 1-Oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylates 10; General Procedure General procedure: A solution of the α-tetralone (10 mmol) in dimethyl carbonate (5 mL) was added to a stirred suspension of NaH (60% dispersion, 15 mmol) in dimethyl carbonate (10 mL) under an atmosphere of argon. The solution was refluxed; when the reaction was complete (TLC monitoring) the solvent was evaporated. The resultant solid was dissolved in 2 M HCl and the phases were separated. The aqueous phase was extracted with EtOAc (3 × 15 mL). The organic extracts were dried (MgSO4) and evaporated to dryness. Flash chromatography (10% EtOAc/hexane) afforded the pure products.
96%	In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; hexane; acetic acid; mineral oil	30 1,2,3,4-Tetrahydro-6-methoxy-1-oxo-2-naphthalenecarboxylic acid, methyl ester EXAMPLE 30 1,2,3,4-Tetrahydro-6-methoxy-1-oxo-2-naphthalenecarboxylic acid, methyl ester A suspension of 24.0 g (0.60 mole) of sodium hydride (60% dispersion in mineral oil) and 49.5 ml (52.9 g; 0.59 mole) of dimethyl carbonate (freshly distilled from sodium hydride) in 240 ml of tetrahydrofuran under a nitrogen atmosphere was stirred and heated to reflux. Reflux was maintained while a solution of 29.7 g (0.17 mole) of 6-methoxy-1-tetralone in 105 ml of tetrahydrofuran was added dropwise over two hours. After addition was complete, the mixture was stirred at reflux for an additional 90 minutes, cooled in ice, and treated dropwise with 36 ml of glacial acetic acid, followed by 450 ml of ice water. The two-phase reaction mixture was extracted with ethyl acetate (4250 ml), and the combined organic layers were washed with water (1600 ml), 5% aqueous sodium bicarbonate solution (3*600 ml), and water again. The ethyl acetate extract was dried (anhydrous sodium sulfate and evaporated (vacuum). The residue was pulverized and stirred in 500 ml of hexane. Filtration yielded 37.9 g (96% yield) of the ester product, mp 79°-81°, suitable for further synthesis. A sample purified by bulb-to-bulb distillation followed by recrystallization from hexane/ethyl acetate was analytically pure, mp 82°-84° (a mp of 88°-89° is given by J. Jacques and A. Horeau, Bull. Soc. Chem. France, 512 (1950)). Calcd. for C13 H14 O4: C, 66.65; H, 6.02; Found C, 66.69; H, 6.00.

94%	With sodium hydride In tetrahydrofuran; mineral oil for 3.5h; Reflux; Inert atmosphere;
88%	With sodium hydride In tetrahydrofuran at 0℃; Inert atmosphere; Reflux;
88%	Stage #1: carbonic acid dimethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 12h; Inert atmosphere; Reflux; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran Inert atmosphere; Stage #3: With acetic acid In tetrahydrofuran	Tetrahydro-6-methoxy-l-oxonaphthalene-2-carboxyIate (SI) A solution of NaH (4.70 g, 323.5 mmol) in anhydrous THF (50 mL) was treated with dimeihylcarbonate (19 mL, 215.6 mmol). The reaction mixture was cooled to 0° C under Al¬ and a solution of 6-methoxy-3 ,4-dihydronaphthalen- 1 (2H)-one (10 g, 56.75 mmol) in THF (10 mL) was added dropwise. The reaction mixture was warmed at reflux for 12 h then quenched with the addition of HO Ac (until pH :=: 7) and diluted with EtOAc. The organic layer was washed with ¾G, saturated aqueous NaCl, and dried over Na2S04. Evaporation in vacuo yielded the crude product that was purified by flash chromatography (Si02, 30% EtOAc-hexanes) to provide the title compound (1 1.70 g, 88%) as a white solid: lH NMR (CDCI3, 500 MHz) δ 7.98 (d, IH, J = 9.0 Hz), 6.81 (dd, IH, J = 2.5, 9.0 Hz), 6.66 (d, 1H, J =2.5 Hz), 3.83 (s, 3H), 3.74 (s, 3H), 3.56-3.53 (m, III), 3.03-2.89 (m, 2H), 2.47-2.43 (m, I H), 2.33-2.30 (m, IH); l3C NMR (CDC13, 125 MHz) δ 191.6, 170.7, 163.8, 146.1 , 130.1 , 125.1 , 1 13.4, 1 12.4, 55.3, 54.0, 52.1 , 27.9, 26.3.
36%	With sodium hydride for 2h; Reflux;	9 Methyl 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate Methyl 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate To a mixture of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (5 g, 28.41 mmol, 1.00 equiv), and dimethyl carbonate (50 mL) was added sodium hydride (1.46 g, 42.58 mmol, 1.50 equiv, 70%) in several batches, and the reaction was heated to reflux for 2 hours. The resulting mixture was concentrated in vacuo and diluted with 50 mL of water. The pH of the aqueous solution was adjusted to 6 with aqueous HCl (1M). The resulting solution was extracted with 3*50 mL of ethyl acetate.The organic layers were combined, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography with EA:PE (1:20) affording 2.4 g (36%) of methyl 6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate as a white solid.
	With sodium hydride In tetrahydrofuran
	With potassium <i>tert</i>-butylate; sodium hydride at 0℃; Inert atmosphere;
	With sodium hydride In mineral oil for 4h; Reflux;
	With sodium hydride In mineral oil for 12h; Reflux;
	With sodium hydride In tetrahydrofuran; mineral oil Reflux;	1. β-keto amides General procedure: β-keto methyl esters were prepared according to the literature procedures (Eur. J. Org. Chem.-6530;).2010, 34, 6525NaH (50 mmol, 2.5 g, 2.5 equiv., 60% dispersion in mineral oil) andanhydrous dimethyl carbonate (DMC, 5 mL)andanhydrous THF (100 mL) were addedsequentially to a dry three-necked flask equipped with a septum, condenser, argon inlet, and alarge stirring egg. The 1-indanone (20 mmol, 1 eq), solubilized in anhydrous THF (20 mL),was added via a dropping funnel for the course of 30 minutes. The heterogeneous mixturewas brought to reflux, and heated for 6 h at this temperature. The reaction was allowed to cooland cautiously quenched at 0 C with H2O (10 mL). The mixture was transferred to aseparative funnel with EtOAc while adding additional 50 mL of 1M HCl. The reaction wasextracted with EtOAc (50 mL x 3) and the combined organic layers washed with a saturatedbrine solution before being dried over solid anhydrous magnesium sulfate and the crudemethyl esters was purified by column chromatography. -keto amides 1a-1v were prepared745).according to the literature procedure (Adv. Synth. Catal. 2016, 358, 737-To a flask equipped with a reflux condenser was added -keto methyl ester (1 mmol), correspondingmmol).amidesR4NH(1.5The mixture was refluxed until complete conversion wasobserved by TLC, then concentrated under reduced pressure and the crude residue waspurified by column chromatography and recrystallization. The 1-indanone derivates werepurchased from Energy-Chemical, Aladdin and Adamas

Reference： [1]Cívicos, José F.; Ribeiro, Carlos M.R.; Costa, Paulo R.R.; Nájera, Carmen [Tetrahedron, 2016, vol. 72, # 16, p. 1897 - 1902]
[2]Cívicos, José F.; Coimbra, Juliana S. M.; Costa, Paulo R. R. [Synthesis, 2017, vol. 49, # 17, p. 3998 - 4006]
[3]Current Patent Assignee: PFIZER INC - US4767776, 1988, A
[4]Geibel, Irina; Christoffers, Jens [European Journal of Organic Chemistry, 2016, vol. 2016, # 5, p. 918 - 920]
[5]Ezzili, Cyrine; Mileni, Mauro; McGlinchey, Nicholas; Long, Jonathan Z.; Kinsey, Steven G.; Hochstatter, Dustin G.; Stevens, Raymond C.; Lichtman, Aron H.; Cravatt, Benjamin F.; Bilsky, Edward J.; Boger, Dale L. [Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 2805 - 2822]
[6]Current Patent Assignee: SCRIPPS RESEARCH - WO2012/106569, 2012, A1 Location in patent: Page/Page column 63-64
[7]Current Patent Assignee: SYNERGENICS LCC - US2012/277224, 2012, A1 Location in patent: Page/Page column 18
[8]Liang, Yu-Feng; Jiao, Ning [Angewandte Chemie - International Edition, 2014, vol. 53, # 2, p. 548 - 552][Angew. Chem., 2014, vol. 53, # 2, p. 558 - 562,5]
[9]Qiu, Jia-Shen; Wang, Yao-Feng; Qi, Gui-Rong; Karmaker, Pran G.; Yin, Hong-Quan; Chen, Fu-Xue [Chemistry - A European Journal, 2017, vol. 23, # 8, p. 1775 - 1778]
[10]Yang, Tonghao; Fan, Xing; Zhao, Xiaopeng; Yu, Wei [Organic Letters, 2018, vol. 20, # 7, p. 1875 - 1879]
[11]Ding, Tianqi; Jiang, Lvqi; Yang, Jie; Xu, Yimin; Wang, Guixiang; Yi, Wenbin [Organic Letters, 2019, vol. 21, # 15, p. 6025 - 6028]
[12]Chen, Pengli; Fu, Yang; Hu, Yanqin; Wang, Shuaifei; Wang, Yakun; Zhang, Conghui; Zhang, Mingwei; Zhao, Ting [Synlett, 2021, vol. 32, # 11, p. 1123 - 1130]

73
[ 1078-19-9 ]
[ 90-15-3 ]
[ 22604-07-5 ]

Yield	Reaction Conditions	Operation in experiment
34%	With hydrogen sulfide; In dichloromethane;	EXAMPLE 1 6-Methoxy-1-naphthalenol A mixture of 50.0 g (0.28 mole) of 6-methoxy-1-tetralone and 9.2 g (0.29 mole) of elemental sulfur was stirred and heated at 250°-260° for three hours (until the evolution of hydrogen sulfide gas had ceased). The mixture was cooled and then subjected to bulb-to-bulb distillation. The distillate was dissolved in 300 ml of dichloromethane, and the solution was extracted with 1.0N potassium hydroxide solution (3*150 ml). The base extracts were combined, cooled in ice, and acidified with 10percent hydrochloric acid to precipitate the crude naphthol product as a gum. Trituration of the gum with tert-butyl methyl ether yielded 16.8 g (34percent yield) of the analytically pure naphthol, mp 84°-86° (a mp of 83°-84° is given by M. P. Sibi, J. W. Dankwardt, and V. Snieckus, J. Org. Chem., 51, 271 (1986)). Calcd. for C11 H10 O2: C, 75.84; H, 5.79. Found C, 75.66; H, 5.69.

Reference： [1]Patent: US4767776,1988,A

74
[ 80567-00-6 ]
[ 1078-19-9 ]
6-methoxy-2-(2,6-dimethylmorpholinomethyl)-1,2,3,4-tetrahydronaphthalen-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With paraformaldehyde;hydrogenchloride; In ethanol;	EXAMPLE 1 This Example illustrates the preparation of 6-methoxy-2-(2,6-dimethylmorpholinomethyl)-1,2,3,4-tetrahydronaphthalene (compound No. 11 of Table 1). 6-Methoxy-1,2,3,4-tetrahydronaphthalen-1-one (17.6 g, 0.1 mol), <strong>[80567-00-6]2,6-dimethylmorpholine hydrochloride</strong> (15.1 g, 0.1 mol), and paraformaldehyde (6.0 g, 0.2 mol) were refluxed together in ethanol (50 ml) with concentrated hydrochloric acid (0.25 ml) as a catalyst for 3 hours. The reaction was cooled and poured into water containing concentrated hydrochloric acid (5 ml) and extracted with ether (200 ml). The aqueous solution was cooled in ice and neutralised with sodium hydroxide solution (10%) then extracted with ether (2*200 ml) dried over magnesium sulphate and evaporated under reduced pressure to give a residue which was recrystallized from petrol (60-80) to give 6-methoxy-2-(2,6-dimethylmorpholinomethyl)-1,2,3,4-tetrahydronaphthalen-1-one a white crystalline solid (10 g, 33% yield) melting at 110 C.

Reference： [1]Patent: US4785006,1988,A

75
[ 26934-35-0 ]
[ 1078-19-9 ]
2-[[4-[3-(Dimethylamino)propoxy]phenyl]methylene]-3,4-dihydro-6-methoxy-1(2H)-naphthalenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In potassium hydroxide; ethanol	5.A (A) (A) 2-[[4-[3-(Dimethylamino)propoxy]phenyl]methylene]-3,4-dihydro-6-methoxy-1(2H)-naphthalenone Interaction of 16 g of 6-methoxy-1-tetralone and 19 g of 4-(3-dimethylaminopropoxy)benzaldehyde in 95 ml of ethanol in the presence of 0.6 g of potassium hydroxide following the procedure described in Example 1A, yields 27 g of crude product; melting point 68-71° C. Following crystallization from 70 ml of diisopropyl ether, the product weighs 18.6 g, melting point 76°-78° C.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US4179558, 1979, A

76
[ 2398-37-0 ]
[ 1078-19-9 ]
[ 96045-09-9 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium t-butanolate In tetrahydrofuran at 32 - 35℃; for 96h; Heating / reflux;	1 Synthesis Preparation 1 l-(4-(2-Piperidinylethoxy)phenoxy)-2-(3-methoxyphenyl)-6-methoxynaphthalene, hydrochlorideTo a 12-L four-neck round-bottom flask equipped with a mechanical stirrer, thermocouple, reflux condenser and a three-way valve connected to a nitrogen source and house vacuum, charge a solution of 6-methoxy-α-tetralone (750 g, 4.26 moles) in tetrahydrofuran (THF; 3750 ml) at ambient temperature. Apply house vacuum until a gentle reflux is observed degassing the solution. Purge the round-bottom with nitrogen via the three-way valve. Repeat this procedure two additional times. Solid bis palladium (0) tris (dibenzylideneacetone) (Pd2(dba)3; 19.5 g, 0.0213 moles, 0.005 eq.) and bis[2- (diphenylphosphino)phenyl]ether (DPE-Phos; 23.0 g, 0.0426 moles, 0.01 eq.) is charged and degas the resulting solution as before. Charge solid sodium t-butoxide (421g, 4.38 moles, 1.03 eq.) and follow immediately by neat 3-bromoanisole (820 g, 555 ml, 4.38 moles, 1.03 eq.). Degas the reaction mixture for a third time, then stir vigorously under positive nitrogen pressure. Allow the reaction to cool to 35 °C then use a heating mantle to maintain a temperature of 320C for four days. Remove the heating mantle and quench the reaction mixture slowly by addition of water (2 L) at such a rate to keep the reaction temperature below 36°C. Transfer the vessel contents to a 22-L bottom-outlet flask equipped with a mechanical stirrer. Charge ethyl Acetate (4 L) and water (4 L) and stir the contents. Isolate the aqueous layer and extract with ethyl acetate (2 L). Combine the organic layers and wash with water (4 L) followed by saturated aqueous sodium chloride (4 L). Dry the organic layer with granular sodium sulfate and filter the mixture directly EPO over a 440-g pad of 100-200 mesh Florisil in a sintered glass funnel (approximately 2 inches deep). Wash the pad with ethyl acetate (2 L) and concentrate the filtrate in vacuo. Dissolve the oil in ter^-butyl methyl ether (4 L) and filter slowly over a 500-g pad of 100- 200 mesh Florisil packed in a sintered funnel (approximately 2 inches). Transfer the filtrate to a 12-L 4-neck flask equipped with a mechanical stirrer and a positive nitrogen inlet. Stir the solution slowly at ambient temperature for 16 hours to form a crystalline mixture. Filter the solid and rinse with methyl ether (500 mL). Dry the material in vacuo at 40°C to yield 844 g (70%) of 6-methoxy-2-(3-methoxyphenyl)-3,4- dihydro-2H-naphthalen-l-one. 1H NMR (DMSOd6, 300 MHz): δ 2.17-2.39 (m, 2H), 2.88-2.96 (m, IH), 3.01-3.12(m,lH), 3.70 (s, 3H), 3.78-3.84 (m, IH), 3.82 (s, 3H), 6.70- 6.78 (m, 2H), 6.79-6.82 (m, IH), 6.89-6.92 (m, 2H), 7.17-7.23 (m, IH), 7.84-7.87 (dd, IH)

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2007/16139, 2007, A2 Location in patent: Page/Page column 7-8

77
[ 1078-19-9 ]
[ 20933-24-8 ]
[ 26231-23-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; dihydrogen peroxide In water at 20℃; for 24h; Irradiation;

Reference： [1]Location in patent: experimental part Podgoršek, Ajda; Stavber, Stojan; Zupan, Marko; Iskra, Jernej [Tetrahedron, 2009, vol. 65, # 22, p. 4429 - 4439]

78
[ 33513-42-7 ]
[ 1078-19-9 ]
[ 883221-31-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In chloroform at 0 - 20℃; for 0.666667h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform at 20℃; for 12h;
80%	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In chloroform at 20℃; for 0.666667h; Inert atmosphere; Cooling with ice; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform at 20℃; for 12h; Inert atmosphere;	General procedure for the synthesis of β-bromo-α,β-unsaturated aldehyde General procedure: A solution of dimethylformamide (5 mmol) inanhydrous chloroform was cooled in ice bath. Phosphorous tribromide (2mmol) was added drop-wise over a period of 10 min. The resulting whitesuspension was warmed to room temperature and stirred for additional 30 min. Asolution of carbonyl compound (1 mmol) in chloroform was added drop-wise and stirred for 12 h at room temperature. The reaction mixture was then poured in icewater. Solid sodium bicarbonate was carefully added to neutralize the acids and the mixture was extracted several times with dichloromethane. The organic partwas then washed with cold water thoroughly, dried with sodium sulphate and evaporated. Purification of the residue was done by silica gel (60-120 mesh)column chromatography to get pure β-bromo-α,β-unsaturated aldehyde
	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In chloroform at 20℃; Cooling with ice; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform at 20℃; for 8.16667h;

	With phosphorus tribromide In chloroform
	With phosphorus tribromide In chloroform at 25℃; for 12h;
	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide at 0℃; Inert atmosphere; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform at 0℃; Inert atmosphere; Reflux;
	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In dichloromethane at 0℃; for 2h; Inert atmosphere; Schlenk technique; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In dichloromethane at 40℃; for 12h; Inert atmosphere; Schlenk technique;
	With phosphorus tribromide
	With boron tribromide In chloroform
	With phosphorus tribromide In chloroform at 0 - 20℃; Inert atmosphere;
	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In chloroform at 0℃; for 0.5h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform at 20℃;	General procedure: To a round-bottomed flask dimethylformamide (3 mmol) and anhydrous chloroform (0.80 mmol) were taken. The flask was cooled down to 0 oC. To the cooled solution was added phosphorous tri bromide (2.7 mmol). The reaction was then left for stirring for a minimum of half hour maintaining the temperature at 0 oC until the formation of a yellow colored solid complex. Next a solution of the tetralones in DMF was added dropwise to the reaction mixture. The reaction was then kept for stirring for overnight at room temperature. After the completion of the reaction, it was quenched with ice cold solution of saturated sodium bicarbonate. The organic part was extracted with DCM several times. Next the organic part was washed with brine and dried over sodium sulphate. Evaporating the organic layer gave the crude product which was purified by column chromatography with silica gel (60-120 mesh). The eluent was petroleum ether/ethyl acetate (50:1).
	Stage #1: N,N-dimethyl-formamide With phosphorus tribromide In chloroform at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In chloroform for 2h; Inert atmosphere; Reflux;

Reference： [1]Gogoi, Junali; Gogoi, Pranjal; Boruah, Romesh C. [European Journal of Organic Chemistry, 2014, vol. 2014, # 16, p. 3483 - 3490]
[2]Gogoi, Junali; Gogoi, Pranjal; Bezbaruah, Pranjal; Boruah, Romesh C. [Tetrahedron Letters, 2013, vol. 54, # 52, p. 7136 - 7139]
[3]Jana, Rathin; Paul, Sunanda; Biswas, Anup; Ray, Jayanta K. [Tetrahedron Letters, 2010, vol. 51, # 2, p. 273 - 276]
[4]Location in patent: scheme or table Yasmin, Nasima; Ray, Jayanta K. [Synlett, 2010, # 6, p. 924 - 930]
[5]Location in patent: scheme or table Paul, Sunanda; Samanta, Shubhankar; Ray, Jayanta K. [Tetrahedron Letters, 2010, vol. 51, # 42, p. 5604 - 5608]
[6]Gogoi, Shyamalee; Shekarrao, Kommuri; Duarah, Aparajita; Bora, Tarun C.; Gogoi, Sanjib; Boruah, Romesh C. [Steroids, 2012, vol. 77, # 13, p. 1438 - 1445]
[7]Shunatona, Hunter P.; Frueh, Natalja; Wang, Yi-Ming; Rauniyar, Vivek; Toste, F. Dean [Angewandte Chemie - International Edition, 2013, vol. 52, # 30, p. 7724 - 7727][Angew. Chem., 2013, vol. 125, # 30, p. 7878 - 7881,4]
[8]Shekarrao, Kommuri; Nath, Dipankar; Kaishap, Partha Pratim; Gogoi, Sanjib; Boruah, Romesh C. [Steroids, 2013, vol. 78, # 11, p. 1126 - 1133]
[9]Yasmin, Nasima; Ghosh, Munmun; Ray, Jayanta K. [RSC Advances, 2014, vol. 4, # 38, p. 19932 - 19938]
[10]Manna, Sudipta Kumar; Panda, Gautam [RSC Advances, 2014, vol. 4, # 40, p. 21032 - 21041]
[11]Ahmed, Atiur; Ray, Jayanta K.; Sarkar, Pompy [Tetrahedron Letters, 2020, vol. 61, # 13]
[12]Deng, Guobo; Jing, Pengyang; Liang, Yun; Sun, Mingjie; Yang, Yuan; Zhou, Fengru; Zhou, Liwei [Organic Letters, 2022, vol. 24, # 6, p. 1400 - 1404]

79
[ 22927-13-5 ]
[ 1078-19-9 ]
[ 1253049-88-5 ]

Reference： [1]European Journal of Medicinal Chemistry,2010,vol. 45,p. 4427 - 4434

80
[ 1078-19-9 ]
[ 703-67-3 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 6488 - 6491

81
[ 100-52-7 ]
[ 17356-08-0 ]
[ 1078-19-9 ]
[ 353268-10-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With (4-sulfobutyl)-tris(4-sulfophenyl)phosphonium hydrogen sulfate at 80℃; for 0.416667h;
85%	With sodium ethanolate In isopropyl alcohol at 20℃; for 0.25h; Sonication;
84%	With trimethylsilyl bromide; iron(III) chloride hexahydrate In acetonitrile at 90℃; for 2h; Microwave irradiation; Sealed tube; Inert atmosphere;	3.2. General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-thiones (4) General procedure: A high-pressure microwave vessel (capacity 10 mL) was loaded with ketones (0.5 mmol),benzaldehydes (0.5 mmol), thiourea (0.75 mmol), FeCl36H2O (0.05 mmol) and TMSBr (0.5 mmol) inCH3CN (3.0 mL). The vessel was degassed, refilled with nitrogen, and sealed. Then the mixture was heated to 90 °C for 2 h under microwave irradiation using a CEM Discover (fixed power, 30 W). After cooling, the solids which had precipitated out were separated by filtration, and the solids obtained were washed with CH3CN to give the desired products 4.

83%	With N-methylpyridinium p-toluenesulfonate In neat (no solvent) at 100 - 110℃; for 3.5h; Green chemistry;
75%	With potassium hydroxide In ethanol for 4h; Reflux;
	With poly(4-vinylpyridinium)hydrogen sulfate In neat (no solvent) at 120℃;
	With poly(4-vinylpyridinium)hydrogen sulfate [P(4-VPH)HSO₄ ] In neat (no solvent) at 120℃; for 0.333333h;	3.2. General procedure for the synthesis of 3-(9-hydroxy-3-methoxy-7-aryl-6,7,9,10-tetrahydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9-yl)-2H-chromen-2-ones (5a-j) General procedure: To a mixture of 6-methoxy-1-tetralone (1, 1 mmol), aryl aldehyde (2a-j, 1 mmol), and thiourea (3, 1 mmol),P(4-VPH)HSO4 (0.015 g) was added and heated at 120° C under neat conditions for 20 min. After consuming of all reactants (confirmed by TLC), to this mixture 3-(2-bromoacetyl)-2H-chromen-2-one (4, 1 mmol) was added and heated at the same temperature for a further 25-40 min. After completion of the reaction as indicated byTLC, 5 mL of ethanol was added and the mixture was stirred at room temperature for an additional 10-15 min.The residue (catalyst) was separated by filtration and the filtrate was concentrated under reduced pressure; the crude product was crystallized from ethanol to aford the pure product.

Reference： [1]Location in patent: experimental part Janardhan, Banothu; Laxmi, Somarapu Vijaya; Rajitha, Bavanthu [Heterocyclic Communications, 2012, vol. 18, # 2, p. 93 - 97]
[2]Location in patent: experimental part Dutta, Mandakini; Gogoi, Junali; Shekarrao, Kommoori; Goswami, Jonalee; Gogoi, Sanjib; Boruah, Romesh Chandra [Synthesis, 2012, vol. 44, # 16, p. 2614 - 2622]
[3]Zhao, Fei; Jia, Xiuwen; Li, Pinyi; Zhao, Jingwei; Huang, Jun; Li, Honglian; Li, Lin [Molecules, 2017, vol. 22, # 9]
[4]Gupta, Richa; Chaudhary, Ram Pal [Journal of Chemical Research, 2012, vol. 36, # 12, p. 718 - 721]
[5]Location in patent: experimental part Gupta, Richa; Chaudhary, Ram Pal [Phosphorus, Sulfur and Silicon and the Related Elements, 2012, vol. 187, # 6, p. 735 - 742]
[6]Janardhan, Banothu; Srinivas, Basavoju; Rajitha, Bavantula; Peter A., Crooks [Tetrahedron Letters, 2014, vol. 55, # 1, p. 224 - 226]
[7]Velpula, Ravibabu; Banothu, Janardhan; Gali, Rajitha; Sargam, Yakaiah; Bavantula, Rajitha [Turkish Journal of Chemistry, 2015, vol. 39, # 3, p. 620 - 629]

82
[ 100-52-7 ]
[ 57-13-6 ]
[ 1078-19-9 ]
3,4,5,6-tetrahydro-8-methoxy-4-phenylbenzo[h]quinazolin-2-(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With (4-sulfobutyl)-tris(4-sulfophenyl)phosphonium hydrogen sulfate at 80℃; for 0.333333h;
81%	With trimethylsilyl bromide; iron(III) chloride hexahydrate In acetonitrile at 90℃; for 2h; Microwave irradiation; Sealed tube; Inert atmosphere;	3.3. General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (6) General procedure: A high-pressure microwave vessel (capacity 10 mL) was loaded with ketones (0.5 mmol),benzaldehydes (0.5 mmol), urea (0.75 mmol), FeCl36H2O (0.05 mmol) and TMSBr (0.5 mmol) in CH3CN (3.0 mL). The vessel was degassed, refilled with nitrogen, and sealed. Then the mixture was heated to 90 °C for 2 h under microwave irradiation using a CEM Discover (fixed power, 30 W). Aftercooling, the solids which had precipitated out were separated by filtration, and the solids obtained were washed with CH3CN to give the desired products 6.

Reference： [1]Location in patent: experimental part Janardhan, Banothu; Laxmi, Somarapu Vijaya; Rajitha, Bavanthu [Heterocyclic Communications, 2012, vol. 18, # 2, p. 93 - 97]
[2]Zhao, Fei; Jia, Xiuwen; Li, Pinyi; Zhao, Jingwei; Huang, Jun; Li, Honglian; Li, Lin [Molecules, 2017, vol. 22, # 9]

83
[ 1078-19-9 ]
[ 40463-28-3 ]

Reference： [1]Patent: US2012/238549,2012,A1

84
[ 1078-19-9 ]
[ 1273666-60-6 ]
[ 26231-23-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide In water at 60℃; for 5h;	6.10 6.10. Synthetic Method FPreparations of 5-bromo-6-methoxy-3,4-dihydronapthalen-1(2H)-one and 2-methoxy-5-oxo-5,6,7,8-tetrahydronaphthalene-1-carbonitrile; In a 100 mL round bottom flask, ketone 5 (5 g, 28.4 mmol) and N-bromosuccinimide (5.05 g, 28.4 mmol) were taken up in water and stirred at 60° C. Then 40% aqueous sulfuric acid (7.6 mL, 56.7 mmol) was added slowly and the reaction mixture was stirred at 60° C. for 5 hours. The reaction mixture was cooled to room temperature and product filtered off and washed twice with water. It was dried over night under vacuum to afford a 3:1 mixture of 5-bromo-6-methoxy-3,4-dihydronapthalene-1(2H)-one 19 and 7-bromo-6-methoxy-3,4-dihydronapthalene-1(2H)-one 20 as a solid, which was directly used in the next step (6.7 g, 92% yield).

Reference： [1]Current Patent Assignee: LEXICON PHARMACEUTICALS INC - US2012/302562, 2012, A1 Location in patent: Page/Page column 11

85
[ 108-90-7 ]
[ 1078-19-9 ]
[ 1769-84-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium t-butanolate;dichloro bis((p-dimethylaminophenyl)-?-di-tert-butylphosphine)palladium(II); In 1,4-dioxane; at 100℃; for 18h;Inert atmosphere;	6-Methoxy-3,4-dihydronaphthalene-1 (2H)-one (I, 352 mg, 2.0 mmol), NaOf-Bu (365 mg, 3.8 mmol) and Pd-1 32 (1 .4 mg, 0.002 mmol) were added to a Schlenk flask. The flask was sealed with a rubber stopper, evacuated and backfilled with nitrogen three times.Chlorobenzene (0.20 mL, 2.0 mmol) followed by dioxane (2.0 mL), was added via airtight syringe through the rubber stopper, and the reaction mixture was stirred at 1 00 C for 18 hours. The reaction mixture was filtered on silica gel and the silica pad was washed with MTBE (20 mL). The filtrate was concentrated to give the desired product as an off-white solid (455 mg, 90%).H NMR (CDCI3) delta = 2.39 - 2.44 (m, 2H), 3.0 - 3.1 (m, 2H), 3.8 (t, 1 H), 3.9 (s, 3H), 6.7 (d, 1 H), 6.9 (dd, 1 H), 7.2 (m, 2H), 7.3 (m, 1 H), 7.4 (m, 2H), 8.1 (d, 1 H) ppm.3C NMR (CDCI3) delta = 28.9, 31 .2, 54.0, 55.4, 1 12.4, 1 13.2, 1 26.4, 1 26.7, 128.35, 1 28.4, 130.2, 140.0, 146.5, 1 63.5, 1 96.9 ppm.

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 17272 - 17276
[2]Patent: WO2012/159981,2012,A2 .Location in patent: Page/Page column 20
[3]Organic and Biomolecular Chemistry,2015,vol. 13,p. 9012 - 9021

86
[ 123-08-0 ]
[ 1078-19-9 ]
[ 124996-03-8 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone With boron trifluoride diethyl etherate In 1,4-dioxane at 20℃; for 0.166667h; Stage #2: 4-hydroxy-benzaldehyde In 1,4-dioxane at 20℃; for 72h;	(a) Representative procedure for synthesis of (E)-2-(4-hydroxybenzylidene)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (3): In a 250mL R.B. Flask 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1, 3g, 17mmol) was stirred in dioxane (20ml) and afterward, BF3·Et2O (0.69ml) was added in the reaction mixture. After stirring for 10min, 4-hydroxybenzaldehyde (2, 2.5g, 8.9mmol) was added in the reaction mixture. The reaction mixture was allowed to stir at room temperature for 72h. The progress of reaction was monitored by thin layer chromatography. After the completion of reaction, the mixture was diluted with ethyl acetate and extracted with water. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to give crude material which on column chromatography on silica gel using 4% ethyl acetate-hexane as eluent gave desired compound (3) as yellow solid; yield 71%; Rf: 0.3 (30% EtOAc in hexane); mp 172-173°C; IR (KBr, νmax/cm-1): 3357 (NH2), 3489 (OH); 1H NMR (acetone-d6, 300MHz, δ ppm): 2.92 (t, 2H, J=6.0Hz, CH2), 3.11 (t, 2H, J=6.0Hz, CH2), 3.88 (s, 3H, OCH3), 6.90 (m, 4H, Ar-H), 7.39 (d, 2H, J=8.4Hz, Ar-H), 7.68 (s, 1H, CH), 7.97 (d, 1H, J=8.4Hz, Ar-H), 9.35 (s, 1H, OH); 13C NMR (acetone-d6, 100MHz, δppm): 27.60, 29.30, 55.58, 112.66, 113.87, 116.05 (2C), 127.50, 127.64, 130.49, 132.36 (2C), 133.54, 136.02, 146.27, 159.04, 164.03, 185.96; m/z; 281 [M+1]+.
61%	With toluene-4-sulfonic acid In ethanol for 24h; Reflux;
29%	With hydrogenchloride In water at 50℃; for 50h;

Reference： [1]Maurya, Hardesh K.; Verma, Ruby; Alam, Saba; Pandey, Shweta; Pathak, Vinay; Sharma, Sandeep; Srivastava, Kishore K.; Negi, Arvind S.; Gupta, Atul [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 21, p. 5844 - 5849]
[2]Ranjbar, Sara; Akbari, Abdolhossein; Edraki, Najmeh; Khoshneviszadeh, Mahsima; Hemmatian, Hajar; Firuzi, Omidreza; Khoshneviszadeh, Mehdi [Letters in drug design and discovery, 2018, vol. 15, # 11, p. 1170 - 1179]
[3]Maurya, Hardesh K.; Hasanain, Mohammad; Singh, Sarita; Sarkar, Jayanta; Dubey, Vijaya; Shukla, Aparna; Luqman, Suaib; Khan, Feroz; Gupta, Atul [RSC Advances, 2016, vol. 6, # 22, p. 18607 - 18618]

87
[ 39627-61-7 ]
[ 1078-19-9 ]
7,7'-dimethyl-2',3'-dihydro-1'H,3H-1,2'-biinden-1'-one [ No CAS ]
2-(6-methoxy-3,4-dihydronaphthalen-1-yl)-7-methyl-2,3-dihydro-1H-inden-1-one [ No CAS ]
6-methoxy-2-(4-methyl-1H-inden-3-yl)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]
[ 97388-54-0 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 24619 - 24634

88
[ 1078-19-9 ]
6,6'-dimethoxy-3,4,3',4'-tetrahydro-1, 1'-binaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With hydrogenchloride; chloro-trimethyl-silane; zinc In tetrahydrofuran at -50℃;
70%	With hydrogenchloride; chloro-trimethyl-silane; zinc In tetrahydrofuran; water at -78 - 25℃; for 9.6h;	2.1 The method for preparing a follows: [0129] 1) In 1000 ml round bottom flask, 61. 6g 6- methoxy-1-tetralone was dissolved in 500ml of tetrahydrofuran, at low temperature after _78 ° C were successively added 45. 5g of zinc powder, 90. 6ml trimethylchlorosilane was added slowly 50ml hydrochloric acid for 10 minutes, 30 minutes after the reaction, the temperature returned to 25 ° C, and reacted at this temperature for 9 hours, dichloromethane and water was added to the reaction mixture which was extracted and the organic phases were combined, dried through MgSO 4 to give compound A 2 (formula III) after the spin dry recrystallized from ethanol 39.5g, 70% yield.
67%	With hydrogenchloride; chloro-trimethyl-silane; zinc at 20℃;

Reference： [1]Sbargoud, Kamal; Mamada, Masashi; Marrot, Jérôme; Tokito, Shizuo; Yassar, Abderrahim; Frigoli, Michel [Chemical Science, 2015, vol. 6, # 6, p. 3402 - 3409]
[2]Current Patent Assignee: Institute of Chemistry (in: CAS); CHINESE ACADEMY OF SCIENCES - CN104529722, 2016, B Location in patent: Paragraph 0127; 0128; 0129
[3]Li, Xiao-Jun; Li, Meng; Yao, Wei; Lu, Hai-Yan; Zhao, Yongsheng; Chen, Chuan-Feng [RSC Advances, 2015, vol. 5, # 24, p. 18609 - 18614]

89
[ 15442-91-8 ]
[ 1078-19-9 ]
C₂₁H₂₀Br₂O₂ [ No CAS ]
C₃₂H₃₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%; 7%		General procedure: To a suspension of sodium hydride (3equiv) in dry THF (20mL), compounds 10a, 10d-f or 10h-i were added and the reaction mixture was stirred at rt for 10min. Later, tetrabromo compound 16 (1.2equiv) was added and the stirring was continued at the same temperature for 8-12h. At the conclusion of the reaction (TLC monitoring), the reaction mixture was quenched with EtOAc and the solvent was removed under reduced pressure. The aqueous layer was extracted with CH2Cl2 and the crude products were purified using appropriate mixtures of EtOAc-petroleum ether to deliver the expected products 14a (39%, 1.09g from 1g of 10a, 12h), 14d (40%, 636mg from 500mg of 10d, 8h), 14e (48%, 285mg from 200mg of 10e, 12h), 14f (44%, 580mg from 500mg of 10f, 20h), 14h (32%, 175mg from 200mg of 10h, 24h) and 14i (36%, 204mg from 300mg of 10i, 15h), along with the dimeric products 17a and 17d-f products. The 1H and 13C NMR spectra of these compounds matched with the literature reported spectral data

Reference： [1]Tetrahedron,2015,vol. 71,p. 6944 - 6955

90
[ 54881-49-1 ]
[ 1078-19-9 ]
C₁₉H₁₇ClO₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 3549 - 3561
[2]Chemical Biology and Drug Design,2016,vol. 88,p. 889 - 898

91
[ 5417-17-4 ]
[ 1078-19-9 ]
C₂₀H₁₉ClO₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 3549 - 3561
[2]Chemical Biology and Drug Design,2016,vol. 88,p. 889 - 898

92
[ 57816-04-3 ]
[ 1078-19-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With Eaton’s reagent In 1,2-dichloro-ethane at 75℃; for 2h; Inert atmosphere;	Method B (Eaton’s Reagent) Eaton’s reagent (1.00 mL, 5.31 mmol) was added slowly to a stirred solution of methyl 4-(3-methoxyphenyl)butanoate (4; 0.37 g, 1.78 mmol) in DCE (1 mL). The resulting mixture was stirred at 75 °C for 2 h under N2 atmosphere. Then, the reaction mixture was allowed to reach room temperature, and was poured over ice-water and extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed successively with brine (2 × 15 mL) and H2O (2 × 20 mL), filtered over Na2SO4 and concentrated under reduced pressure. The resulting brownish oil was fractionated by column chromatography (silica gel, EtOAc-hexanes, 1:9) to obtain 6-methoxy-1-tetralone (2) as ayellowish oil; yield: 0.28 g (91%). IR (ATR): 2947, 1670, 1590, 1249, 832 cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.00 (d, J8-7 = 8.7 Hz, 1 H, H-8), 6.82(dd, J7-8 = 8.7 Hz, J7-5 = 2.5 Hz, 1 H, H-7), 6.71 (d, J5-7 = 2.5 Hz, 1 H, H-5), 3.85 (s, 3 H, OMe), 2.93 (dd, Jgem = J4-3 = 6.0 Hz, 2 H, H-4), 2.61 (dd,Jgem = J2-3 = 6.0 Hz, 2 H, H-2), 2.11 (ddd, Jgem = J3-2 = J3-4 = 6.0 Hz, 2 H, H-3). 13C NMR (75 MHz, CDCl3): δ = 197.3 (Q, C-1), 163.6 (Q, C-6), 147.0 (Q,C-10), 129.7 (CH, C-8), 126.3 (Q, C-9), 113.0 (CH, C-5), 112.6 (CH, C-7),55.5 (CH3, OMe), 38.9 (CH2, C-2), 30.2 (CH2, C-4), 23.4 (CH2, C-3). MS: m/z (%) = 176 (78) [M+], 148 (100), 120 (50), 91 (22), 77 (24). HRMS (ESI): m/z [M + H+] calcd for C11H12O2: 176.0832; found:176.0845.

Reference： [1]Castillo-Rangel, Norma; Pérez-Díaz, José Oscar H.; Vázquez, Alfredo [Synthesis, 2016, vol. 48, # 13, p. 2050 - 2056]

93
[ 443-69-6 ]
[ 4149-06-8 ]
[ 1078-19-9 ]
5'-fluoro-3-methoxy-9-phenyl-6,9,10,11-tetrahydrospiro[benzo[h]pyrazolo[3,4-b]quinoline-7,3'-indoline]-2',8(5H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With acetic acid; In water; at 90℃; for 5h;Green chemistry;	General procedure: The mixture of isatin (1 mmol), <strong>[4149-06-8]3-amino-1-phenyl-1H-pyrazol-5(4H)-one</strong> (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.

Reference： [1]Tetrahedron,2017,vol. 73,p. 385 - 394

94
[ 4149-06-8 ]
[ 17630-76-1 ]
[ 1078-19-9 ]
5'-chloro-3-methoxy-9-phenyl-6,9,10,11-tetrahydrospiro[benzo[h]pyrazolo[3,4-b]quinoline-7,3'-indoline]-2',8(5H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With acetic acid; In water; at 90℃; for 6h;Green chemistry;	General procedure: The mixture of isatin (1 mmol), <strong>[4149-06-8]3-amino-1-phenyl-1H-pyrazol-5(4H)-one</strong> (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.

Reference： [1]Tetrahedron,2017,vol. 73,p. 385 - 394

95
[ 7477-63-6 ]
[ 4149-06-8 ]
[ 1078-19-9 ]
7'-chloro-3-methoxy-9-phenyl-6,9,10,11-tetrahydrospiro[benzo[h]pyrazolo[3,4-b]quinoline-7,3'-indoline]-2',8(5H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic acid; In water; at 90℃; for 6h;Green chemistry;	General procedure: The mixture of isatin (1 mmol), <strong>[4149-06-8]3-amino-1-phenyl-1H-pyrazol-5(4H)-one</strong> (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.

Reference： [1]Tetrahedron,2017,vol. 73,p. 385 - 394

96
[ 317-20-4 ]
[ 4149-06-8 ]
[ 1078-19-9 ]
7'-fluoro-3-methoxy-9-phenyl-6,9,10,11-tetrahydrospiro[benzo[h]pyrazolo[3,4-b]quinoline-7,3'-indoline]-2',8(5H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic acid; In water; at 90℃; for 5h;Green chemistry;	General procedure: The mixture of isatin (1 mmol), 3-amino-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.

Reference： [1]Tetrahedron,2017,vol. 73,p. 385 - 394

97
[ 2826-26-8 ]
[ 1078-19-9 ]
2-amino-5,6-dihydro-8-methoxy-4-(4-methoxyphenyl)benzo[h]quinoline-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With ammonium acetate; acetic acid In ethanol for 12h; Reflux;	General Procedure to Obtain Derivatives 4-7(a-m) General procedure: A solution of tetralone (2.0 mmol) and benzylidenemalononitrile (3.08 mmol) respectives in ethanol 10 mL and acetic acid catalytic amount was refluxed for 12h. The solid formed on cooling was collected, washed with diethyl ether and recrystallized from ethanol.
75%	With piperidine; ammonium acetate In ethanol at 130℃; for 0.25h; Microwave irradiation;	2.3.12. General procedure for the synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenyl (or substituted phenyl) benzo [h] quinoline-3-carbonitrile 6a-e General procedure: A mixture of suitable 2-substituted arylidenemalononitriles(0.001 mol), namely; 2-Benzylidene malononitrile, 2-((furan-2-yl)methylene) malononitrile, 2-(4-chlorobenzylidene) malononitrile,2-(3,4,5-trimethoxybenzylidene) malononitrile, and/or 2-(4-methoxybenzylidene) malononitrile, in ethanol (3 mL), wereadded to a mixture of 6-methoxy-1-tetralone (1) (0.001 mol),ammonium acetate (0.002 mol), and few drops of piperidine. Thereaction mixture was subjected to microwave irradiation at 130 C,(400W) for ~ 15 min. Completion of the reaction (was monitored byTLC), after cooling the product was filtered, and recrystallized fromdilute ethanol to give compounds 6a-e.

Reference： [1]Mata, Gricelda; Rodrigues, Juan; Gamboa, Neira; Charris, Katiuska; Lobo, Gricela; Monasterios, Melina; Avendaño, Milagros; Lein, Michael; Jung, Klaus; Abramjuk, Claudia; Nitzsche, Bianca; Höpfner, Michael; Charris, Jaime [Letters in drug design and discovery, 2017, vol. 14, # 4, p. 398 - 413]
[2]Haiba, Mogedda E.; Al-Abdullah, Ebtehal S.; Ahmed, Nesreen S.; Ghabbour, Hazem A.; Awad, Hanem M. [Journal of Molecular Structure, 2019, vol. 1195, p. 702 - 711]

98
[ 5688-82-4 ]
[ 1078-19-9 ]
2-amino-5,6-dihydro-8-methoxy-4-(3,4,5-trimethoxyphenyl)benzo[h]quinoline-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With piperidine; ammonium acetate In ethanol at 130℃; for 0.25h; Microwave irradiation;	2.3.12. General procedure for the synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenyl (or substituted phenyl) benzo [h] quinoline-3-carbonitrile 6a-e General procedure: A mixture of suitable 2-substituted arylidenemalononitriles(0.001 mol), namely; 2-Benzylidene malononitrile, 2-((furan-2-yl)methylene) malononitrile, 2-(4-chlorobenzylidene) malononitrile,2-(3,4,5-trimethoxybenzylidene) malononitrile, and/or 2-(4-methoxybenzylidene) malononitrile, in ethanol (3 mL), wereadded to a mixture of 6-methoxy-1-tetralone (1) (0.001 mol),ammonium acetate (0.002 mol), and few drops of piperidine. Thereaction mixture was subjected to microwave irradiation at 130 C,(400W) for ~ 15 min. Completion of the reaction (was monitored byTLC), after cooling the product was filtered, and recrystallized fromdilute ethanol to give compounds 6a-e.
89%	With ammonium acetate; acetic acid In ethanol for 12h; Reflux;	General Procedure to Obtain Derivatives 4-7(a-m) General procedure: A solution of tetralone (2.0 mmol) and benzylidenemalononitrile (3.08 mmol) respectives in ethanol 10 mL and acetic acid catalytic amount was refluxed for 12h. The solid formed on cooling was collected, washed with diethyl ether and recrystallized from ethanol.

Reference： [1]Haiba, Mogedda E.; Al-Abdullah, Ebtehal S.; Ahmed, Nesreen S.; Ghabbour, Hazem A.; Awad, Hanem M. [Journal of Molecular Structure, 2019, vol. 1195, p. 702 - 711]
[2]Mata, Gricelda; Rodrigues, Juan; Gamboa, Neira; Charris, Katiuska; Lobo, Gricela; Monasterios, Melina; Avendaño, Milagros; Lein, Michael; Jung, Klaus; Abramjuk, Claudia; Nitzsche, Bianca; Höpfner, Michael; Charris, Jaime [Letters in drug design and discovery, 2017, vol. 14, # 4, p. 398 - 413]

99
[ 5688-82-4 ]
[ 1078-19-9 ]
2-amino-8-methoxy-4-(3,4,5-trimethoxyphenyl)-5,6-dihydro-4H-benzo[h]chromene-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With piperidine In ethanol at 130℃; for 0.25h; Microwave irradiation;	2.3.2. General procedure for the synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenyl (or substituted phenyl)-4H-benzo [h]chromene-3-carbonitrile 2a-e General procedure: A mixture of 2-substituted arylidenemalononitriles (0.001 mol),namely; 2-Benzylidene malononitrile, 2-((furan-2-yl) methylene)malononitrile, 2-(4-chlorobenzylidene) malononitrile, 2-(3,4,5-trimethoxybenzylidene) malononitrile, or 2-(4-methoxybenzylidene) malononitrile, in ethanol (3 mL), were addedto a mixture of 6-methoxy-1-tetralone (1) (0.001 mol), and fewdrops of piperidine. The reaction mixture was subjected to microwaveirradiation at 130 C, (400W) for ~ 15 min. Completion of thereaction (was monitored by TLC). After cooling the product wasfiltered, and recrystallized from dilute ethanol to give compounds2a-e.
48%	With piperidine In ethanol for 12h; Reflux;	General Procedure to Obtain Derivatives 3a-d General procedure: A solution of tetralone respective (2.0 mmol) and 3,4,5-trimethoxybenzylidenemalononitrile (3.08 mmol) in ethanol 10 mL and piperidine catalytic amount was refluxed for 12h. The solid formed on cooling was collected, washed with diethyl ether and recrystallized from ethanol.

Reference： [1]Haiba, Mogedda E.; Al-Abdullah, Ebtehal S.; Ahmed, Nesreen S.; Ghabbour, Hazem A.; Awad, Hanem M. [Journal of Molecular Structure, 2019, vol. 1195, p. 702 - 711]
[2]Mata, Gricelda; Rodrigues, Juan; Gamboa, Neira; Charris, Katiuska; Lobo, Gricela; Monasterios, Melina; Avendaño, Milagros; Lein, Michael; Jung, Klaus; Abramjuk, Claudia; Nitzsche, Bianca; Höpfner, Michael; Charris, Jaime [Letters in drug design and discovery, 2017, vol. 14, # 4, p. 398 - 413]

100
[ 86-81-7 ]
[ 1078-19-9 ]
(E)-2-(3,4,5-trimethoxybenzylidene)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium methylate In methanol at 20℃;	Synthesis of benzylidene tetralones 1-6; general procedure General procedure: A mixture of α-tetralone respective (1 mmol), an appropriate benzaldehyde (1 mmol) and sodium methoxide (catalytic) in methanol(8 mL) was stirred at room temperature over night. Water was addedand the resulting precipitate was collected by filtration, washed withwater and recrystallised from methanol.
90%	With potassium hydroxide In methanol at 20℃; for 12h;
84%	With toluene-4-sulfonic acid In ethanol for 24h; Reflux;

Reference： [1]Aparicio, Daniel A.; Lobo, Gricela M.; Sánchez, Jennifer L.; Monasterios, Melina C.; Acosta, María E.; De Lima, Lola; Llovera, Ligia J.; Ángel, Jorge E.; Charris, Jaime E. [Journal of Chemical Research, 2017, vol. 41, # 11, p. 668 - 672]
[2]Maguire, Casey J.; Carlson, Graham J.; Ford, Jacob W.; Strecker, Tracy E.; Hamel, Ernest; Trawick, Mary Lynn; Pinney, Kevin G. [MedChemComm, 2019, vol. 10, # 8, p. 1445 - 1456]
[3]Ranjbar, Sara; Akbari, Abdolhossein; Edraki, Najmeh; Khoshneviszadeh, Mahsima; Hemmatian, Hajar; Firuzi, Omidreza; Khoshneviszadeh, Mehdi [Letters in drug design and discovery, 2018, vol. 15, # 11, p. 1170 - 1179]

101
[ 70201-43-3 ]
[ 1078-19-9 ]
[ 1620646-31-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydroxide; In ethanol; at 35℃; for 4h;	At 35 C, to a solution of NaOH (0.39 g, 9.7 mmol) in EtOH(12 mL) were added in one portion a mixture of 6,7-dimethoxy-1-tetralone 1c (1.0 g, 4.85 mmol) and <strong>[70201-43-3]3-bromo-4-pyridinecarboxaldehyde</strong>2 (0.9 g, 4.85 mmol). The reaction mixture was then stirredfor 4 h at the same temperature. The resulting precipitate was filtered off then rinsed twice with cold diethyl ether to afford thetitle compound 3c as a pale yellow solid. (Yield 1.80 g, 99%). 1H NMR(300 MHz, CDCl3, d): 2.89 (br s, 4H); 3.92 (s, 6H), 6.65 (s, 1H), 7.17 (d,1H, J 5.1 Hz), 7.60 (s, 2H), 8.51 (d, 1H, J 5.1 Hz), 8.75 (s, 1H). 13CNMR (75 MHz, CDCl3, d): 27.7, 28.6, 56.1, 56.2, 109.6, 110.0, 122.6,124.5, 126.1, 131.6, 139.5, 144.5, 148.0, 148.5, 152.3, 154.1, 185.7.HRMS (ESI): calcd for [MH] C18H17NO3Br m/z 374,0392; found374.0392.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 145,p. 165 - 190

102
[ 1950-68-1 ]
[ 1078-19-9 ]
4-methoxy-N'-(6-methoxy-3,4-dihydronaphthalen-1(2H)-ylidene)benzenesulfonohydrazide [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2019,vol. 2019,p. 753 - 758

103
[ 1078-19-9 ]
[ 116632-05-4 ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 4596 - 4600
Angew. Chem.,2019,vol. 131,p. 4644 - 4648,5

104
[ 67-56-1 ]
[ 1078-19-9 ]
[ 27752-24-5 ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 10472 - 10480
[2]European Journal of Organic Chemistry,2019,vol. 2019,p. 3694 - 3698

105
[ 586-61-8 ]
[ 1078-19-9 ]
2-(4-isopropylphenyl)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 5,5-dimethyl-1,3-cyclohexadiene; at 130℃; for 24h;Sealed tube;	To a solution of 6-methoxy-3,4-dihydronaphthalen-l(2H)-one L31-1 (5 g, 28.41 mmol) in xylene (125 mL) was added l-bromo-4-isopropylbenzene (6.78 g, 34.07 mmol) followed by cesium carbonate (32.4 g, 99.41 mmol) and degassed with argon for 15 min in a sealed tube. To the resulting solution was added Pd(OAc)2(636 mg, 2.839 mmol) and Xanthphos (2.5 g, 4.251 mmol) and degassing was continued for another 15 min. Then the reaction mixture was sealed properly and heated to l30C for 24 h. After completion of the reaction (monitored by TLC and LCMS), the reaction mixture was filtered through a pad of Celite and the filtrate was concentrated under reduced pressure. The resulting crude compound was purified by silica gel column chromatography eluting with 0-10% ethyl acetate in -hexane to afford 2.5 g (30% yield) of compound L31-2 as brown oil.LCMS-Condition-1 : [M + H]+= 295.05; Rt = 2.22 min?H NMR (400 MHz, DMSO-ifc) d: 7.87 (d, J= 8.31 Hz, 1H), 7.15-7.20 (m, 2H), 7.08 (d, J = 8.31 Hz, 2H), 6.89-6.94 (m, 2H), 3.84 (s, 3H), 3.80 (dd, = 4.89, 11.25 Hz, 1H), 3.02-3.13 (m, 1H), 2.82-2.98 (m, 2H), 2.20-2.36 (m, 2H), 1.20 (d, J= 6.85 Hz, 6H).

Reference： [1]Patent: WO2019/144132,2019,A1 .Location in patent: Paragraph 000266; 000444

106
[ 5973-83-1 ]
[ 1078-19-9 ]
7-methoxy-3-(3-pyridinyl)-4,5-dihydrobenzo[g]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 1-(pyridin-3-yl)ethan-1-one oxime With sodium hydride; p-toluenesulfonyl chloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran at 50℃; for 8h; Inert atmosphere;	5 Synthesis of 7-methoxy-3-(3-pyridinyl)-4,5-dihydrobenzo[g]indole: In a N2 protected ice water bath, 1-(3-pyridine)-1-ethanoneoxime (6.9 mmol) dissolved in THF was slowly added to a THF mixed system of NaH (27.6 mmol), and TsCl (6.9 mmol) dissolved in THF was slowly added. After stirring at room temperature for 0.5 hours, 6-methoxy-1-naphthylenone (6.9 mmol) dissolved in THF was slowly added, stirred at room temperature for 2 hours, and stirred at 50 °C for 6 hours. Quenching with ice water, extraction with dichloromethane, drying with sodium sulfate, and silica gel column chromatography gave 7-methoxy-3-(3-pyridine)-4,5-dihydrobenzo[g]indole. Yield(70%).

Reference： [1]Current Patent Assignee: HENAN UNIVERSITY - CN110283159, 2019, A Location in patent: Paragraph 0045-0050

107
[ 6793-92-6 ]
[ 1078-19-9 ]
4-(4-(benzyloxy)phenyl)-7-methoxy-1,2-dihydronaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	Stage #1: p-benzyloxyphenylbromide With iodine; magnesium In tetrahydrofuran at 60℃; for 0.75h; Stage #2: 6-methoxy-3,4-dihydro-1(2H)-naphthalenone In tetrahydrofuran at 40 - 65℃; for 3h;	22 4-(4-(Benzyloxy)phenyl)-7-methoxy-l,2-dihydronaphthalene . The Grignard reagent was synthesized following the procedure described in Res. Chem. Intermed. 2009, 35, 615-623. A suspension of Mg turnings (321 mg, 13.38 mmol) with a crystal of iodine in THF (7 mL) was placed in ultrasonic bath at 45 °C for 30 minutes. The flask was then moved to a silicon oil bath and stirred at 60 °C for 40 minutes, resulting in a change of color (from purple to pale yellow). A solution of 4-benzyloxybromobenzene (3.2g, 12.17 mmol, prepared as in Chem. Eur. J. 2016, 22, 16721-16276) in THF (10 mL) was then added dropwise at 60 °C. After stirring at 60 °C for 45 minutes the solution became light brown as a result of the formation of the Grignard reagent, after which the reaction mixture was cooled to 40 °C. A solution of 6-methoxy-l-tetralone (4.3g, 24.40 mmol) in THF (15 mL) was added drop by drop to the previous solution. The reaction was kept at 65 °C for 3 h, thereafter cooled to 0 °C and quenched with HC1 (1M, 200 mL, pH 2). The aqueous layer was extracted with CH2CI2 (3 x 100 mL) and the combined organic fractions were washed with brine (200 mL) and dried (Na2S04). After removal of the solvent the mixture was subjected to column chromatography (silica gel, CHiCh/Hex, 1 :4 to 9: 1) to provide the product as a white solid (1.12 g, 28%). NMR (400 MHz, CDCb) d 7.49 - 7.44 (m, 2H), 7.43 - 7.38 (m, 2H), 7.38 - 7.29 (m, 1H), 7.29 - 7.25 (m, 2H), 7.00 - 6.94 (m, 3H), 6.77 (d, J= 2.8 Hz, 1H), 6.64 (dd, J= 8.7, 2.4 Hz, 1H), 5.91 (t, 7= 4.5 Hz, 1H), 5.10 (s, 2H), 3.80 (s, 3H), 2.81 (t, 7= 7.7 Hz, 2H), 2.40 - 2.33 (m, 2H). 13C NMR (100 MHz, CDCb) d 158.7, 158.2, 139.0, 138.8, 137.3, 133.9, 129.9, 128.7, 128.1, 127.6, 126.7, 124.6, 114.7, 113.9, 110.8, 70.2, 55.4, 29.0, 23.6

Reference： [1]Current Patent Assignee: MEMORIAL SLOAN-KETTERING CANCER CENTER - WO2019/241231, 2019, A1 Location in patent: Paragraph 0091

108
[ 4649-09-6 ]
[ 1078-19-9 ]
(E)-2-((1H-pyrrolo[2,3-b]pyridin-3-yl)methylene)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydrogenchloride; In methanol; water; at 60 - 80℃; for 6h;	General procedure: To a solution of (7) 1-(<strong>[4649-09-6]1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde</strong> (0.300g, 2.053mmol) in 32% aqueous HCl/methanol (1.5:1 v/v) (4.5ml/3 ml) was added a selected bicyclic scaffold (tetralone, indanone, 3-coumaranone, 4-chromanone and thiochroman-4-one) (2.053mmol) and the reaction was refluxed for at least 6h at 60-80C. The progress of the reaction was monitored by silica gel TLC with ethyl acetate as mobile phase. When the reaction reached completion, the target products were isolated by precipitation with ice-cold water, after which they were purified by recrystallisation with ethanol.

Reference： [1]Bioorganic and medicinal chemistry,2020

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1078-19-9	MDL No. :	MFCD00001695
Formula :	C₁₁H₁₂O₂	Boiling Point :	-
Linear Structure Formula :	C₆H₃(OCH₃)C₄H₆O	InChI Key :	MNALUTYMBUBKNX-UHFFFAOYSA-N
M.W :	176.21	Pubchem ID :	14112
Synonyms :		Chemical Name :	6-Methoxy-3,4-dihydronaphthalen-1(2H)-one

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.36
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.79
TPSA :	26.3 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.96 cm/s

Log Po/w (iLOGP) :	2.15
Log Po/w (XLOGP3) :	1.99
Log Po/w (WLOGP) :	2.21
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	3.0
Consensus Log Po/w :	2.2

[ CAS No. 1078-19-9 ] {[proInfo.proName]}

Quality Control of [ 1078-19-9 ]

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Calculated chemistry of [ 1078-19-9 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1078-19-9 ]

Application In Synthesis of [ 1078-19-9 ]

[ 1078-19-9 ] Synthesis Path-Upstream 1~13

[ 1078-19-9 ] Synthesis Path-Downstream 1~108

Technical Information

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.46
Solubility :	0.609 mg/ml ; 0.00345 mol/l
Class :	Soluble
Log S (Ali) :	-2.17
Solubility :	1.2 mg/ml ; 0.00678 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.52
Solubility :	0.0532 mg/ml ; 0.000302 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.72

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
91%	With sodium t-butanolate In toluene at 60℃; for 18 h; Inert atmosphere	Scheme 2 ynthesis of 6-methoxy-2-phenyl-3,4-dihvdronaphthalene-1 (2H)-oneA)91 percent crude yield98percent HPLC purity6-Methoxy-3,4-dihydronaphthalene-1 (2H)-one (I, 352 mg, 2.0 mmol), NaOf-Bu (365 mg, 3.8 mmol) and Pd-132 (14 mg, 0.02 mmol) were added to a Schlenk flask. The flask was sealed with a rubber stopper, evacuated and backfilled with nitrogen three times. Bromobenzene (0.21 mL, 2.0 mmol) followed by toluene (2.0 mL), was added via airtight syringe through the rubber stopper, and the reaction mixture was stirred at 60 °C for 18 hours. The reaction mixture was filtered on silica gel and the silica pad was washed with MTBE (20 mL). The filtrate was concentrated to give the desired product as an off-white solid (461 mg, 91 percent). H NMR (CDCI₃) δ = 2.39 - 2.44 (m, 2H), 3.0 - 3.1 (m, 2H), 3.8 (t, 1 H), 3.9 (s, 3H), 6.7 (d, 1 H), 6.9 (dd, 1 H), 7.2 (m, 2H), 7.3 (m, 1 H), 7.4 (m, 2H), 8.1 (d, 1 H) ppm.3C NMR (CDCI₃) δ = 28.9, 31 .2, 54.0, 55.4, 1 12.4, 1 13.2, 1 26.4, 1 26.7, 128.35, 1 28.4, 130.2, 140.0, 146.5, 1 63.5, 1 96.9 ppm.
91%	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); sodium t-butanolate In toluene at 60℃; for 18 h; Schlenk technique; Inert atmosphere	4.2.1.1. From bromobenzene. Tetralone 1 (352 mg, 2.0 mmol), NaOt-Bu (365 mg, 3.8 mmol) and Pd-132 (14 mg, 0.02 mmol) wereadded to a Schlenk flask. The flask was sealed with a rubber stopper,evacuated and backfilled with nitrogen three times. Bromobenzene(0.21 mL, 2.0 mmol) followed by toluene (2.0 mL),was added via airtight syringe through the rubber stopper, andthe reaction mixture was stirred at 60 C for 18 h. The reactionmixture was filtered through silica gel and the silica pad waswashed with MTBE (20 mL). The filtrate was concentrated to givethe desired product 2 as an off-white solid (461 mg, 91percent).