Name: 4753-59-7|4-Bromobutyl acetate|98%
Brand: Ambeed
SKU: A217982
Price: 10.0 USD
Availability: InStock
Rating: 99 (28 reviews)

1
[ 109-99-9 ]
[ 506-96-7 ]
[ 4753-59-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	at 0℃;
85%
81%	In tetrahydrofuran for 24h; Ambient temperature;

78%	With zinc(II) chloride at 120℃;
	With zinc(II) chloride
	With tin(IV) chloride
	Heating;
	With zinc dibromide
	With zinc dibromide Heating;
189.6 g	at 100 - 115℃; for 2h;
	With zinc dibromide Heating;

Reference： [1]Lazrek, H. B.; Taourirte, M.; Barascut, J. L.; Imbach, J. L. [Bulletin des Societes Chimiques Belges, 1996, vol. 105, # 7, p. 391 - 396]
[2]Kovalev, B. G.; Matveeva, E. D.; Stan, V. V.; Vovk, G. A.; Yudin, L. G.; Kost, A. N. [Journal of Organic Chemistry USSR (English Translation), 1980, vol. 16, # 10, p. 1728 - 1733][Zhurnal Organicheskoi Khimii, 1980, vol. 16, # 10, p. 2032 - 2038]
[3]Fitch, John W.; Payne, Wyatt G.; Westmoreland, Donald [Journal of Organic Chemistry, 1983, vol. 48, # 5, p. 751 - 753]
[4]Lee; Hashimoto; Ohta; Shudo; Okamoto [Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 8, p. 3046 - 3049]
[5]Borowitz,I.J. et al. [Journal of Organic Chemistry, 1968, vol. 33, # 5, p. 2013 - 2020] Cloke; Pilgrim [Journal of the American Chemical Society, 1939, vol. 61, p. 2668]
[6]Smorgonskii; Gol'dfarb [Zhurnal Obshchei Khimii, 1940, vol. 10, p. 1113,1115][Chemisches Zentralblatt, 1940, vol. 111, # II, p. 3472]
[7]Arbuzov,B.A.; Yarmukhametova,D.Kh. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1960, p. 1645 - 1648][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1960, p. 1767 - 1771]
[8]Ispiryan,R.M. et al. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1967, p. 2391 - 2398][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1967, # 11, p. 2513 - 2522] Gol'dfarb,Ya.L. et al. [Doklady Chemistry, 1967, vol. 173, p. 209 - 212][Doklady Akademii Nauk SSSR, 1967, vol. 173, p. 97 - 100] Zorin, V. V.; Batyrbaev, N. A.; Zlot-skii, S. S.; Rakhmankulov, D. L. [Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, p. 347 - 352][Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 2, p. 387 - 393] Lazrek; Taourirte; Oulih; Lebtoumi; Barascut; Imbach [Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1115 - 1118]
[9]Mosset, Paul; Gree, Rene; Falck, J. R. [Synthetic Communications, 1989, vol. 19, # 3and4, p. 645 - 658]
[10]Gruiec, Regine; Noiret, Nicolas; Patin, Henri [Bulletin de la Societe Chimique de France, 1994, vol. 131, # 6, p. 699 - 705]
[11]Lis, L. G.; Filich, E. R.; Zheldakova, T. A. [Russian Journal of Organic Chemistry, 1994, vol. 30, # 11.1, p. 1729 - 1734][Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 11, p. 1644 - 1649]
[12]Carrington, Simon; Renault, Jacques; Tomasi, Sophie; Corbel, Jean-Charles; Uriac, Philippe; Blagbrough, Ian S. [Chemical Communications, 1999, # 14, p. 1341 - 1342]

2
[ 109-99-9 ]
[ 64-19-7 ]
[ 4753-59-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogen bromide In tetrahydrofuran at 10℃; for 4h;	2 Example 2: Preparation of 4-bromo-1-acetoxylbutane 460 mL of tetrahydrofuran was added to a 1000 mL four-neck flask and cooled to 10° C. by ice-water bath, 280 g acetic acid solution of hydrogen bromide with its mass content of 33% was added dropwise, then the mixture was kept at 10° C. for 4 hours to react until the reaction was completed. Tetrahydroffiran and acetic acid were recovered by vacuum distillation, the residue was heated to 100° C. and distilled at 2 mmHg vacuum, then 87 to 89° C. component fraction was collected to obtain 206 g of colorless clear liquid of 4-bromo-1 -acetoxyl butane. The molar yield: 93%, GC purity: 99.5%. ‘H-NMR data: (400 MHz, CDC13) ö: 4.05 (t, J=6.4 Hz, 2H), 3.39 (t, J=6.8 Hz, 2H), 1.99 (s, 3H), 1.86 (m, 2H), 1.75 (m, 2H).
85%	With phosphorus tribromide; zinc(II) chloride at 20 - 90℃;	4-Bromobutyl acetate It was prepared according to the reported procedure. 23 light yellow liquid 27.6 g, yield 85%. 1H NMR (400 MHz,DMSO-d6, ppm) δ 4.03 (t, J = 6.8 Hz, 2H), 3.42 (t, J =6.4 Hz, 2H), 2.01 (s, 3H), 1.81-1.88 (m, 2H), 1.50-1.57 (m, 2H). 13C NMR (101 MHz, DMSO-d6, ppm) δ 171.2, 67.7,36.0, 31.6, 29.9, 25.8.
	With hydrogen bromide at 20℃; for 1h;	4 A 33% HBr solution in acetic acid was added to tetrahydrofuran (14). After 1 hour stirring at room temperature, solvents were evaporated under a gentle nitrogen stream. The pure 4-bromobutyl acetate (15) has been obtained.

With hydrogen bromide

Reference： [1]Current Patent Assignee: SEASONS BIOTECHNOLOGY; SHANGHAI SHIJI BIOLOG TECHNOLOGY; SHANGHAI SEASONS BIOTECHNOLOGY; SEASONS BIOTECHNOLOGY TAIZHOU - US2018/29973, 2018, A1 Location in patent: Paragraph 0039; 0040; 0041; 0042; 0043; 0044; 0045-0050
[2]Zhou, Jianjun; Xiao, Yan; Chen, Taiping; Gao, Jiyu; Huang, Wencai; Li, Zicheng [Journal of Chemical Research, 2021, vol. 45, # 3-4, p. 310 - 314]
[3]Current Patent Assignee: GOVERNMENT OF THE NETHERLANDS - US2014/17797, 2014, A1 Location in patent: Paragraph 0153
[4]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE725528, 1940, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

3
[ 110-91-8 ]
[ 4753-59-7 ]
[ 5835-79-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1959,vol. 29,p. 631,632; engl. Ausg. S. 626, 627

4
[ 109-99-9 ]
[ 75-36-5 ]
[ 4753-59-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: tetrahydrofuran With potassium bromide In acetonitrile at 0℃; Stage #2: acetyl chloride In acetonitrile at 20℃;
85%	With potassium bromide In acetonitrile at 0 - 20℃; for 36h;	Synthesis of 4-bromobutyl acetate (2) Synthesis of 4-bromobutyl acetate (2) (0062) Tetrahydrofuran (12.2 mL, 148.4 mmol) and potassium bromide (21.1 g, 176.5 mmol) were added in a 250 mL round bottom flask containing 150 mL acetonitrile. The reaction mixture was cooled to 0° C., followed by drop-wise addition of acetyl chloride (11 mL, 155.1 mmol). Subsequently, the mixture was brought to room temperature, where it was continuously stirred for 36 h. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, and concentrated to obtain the pure product as a colorless liquid. (0063) Yield: 24.3 g (85%). bp: >250° C. 1H NMR (300 MHz, CDCl3, δ ppm, J Hz): 1.79 (m, 2H), 1.92 (m, 2H), 2.03 (s, 3H), 3.46 (t, 2H. J=7.6), 4.08 (t, 2H. J=6.7). 13C NMR (75 MHz, CDCl3, δ ppm): 20.87, 27.36, 29.36, 33.03, 63.43, 170.95. IR (CHCl3): 3038, 2926, 1352, 1243, 1052 cm-1.
	With copper(ll) bromide In tetrahydrofuran at 20℃; for 8h;

With potassium bromide In acetonitrile at 0 - 20℃; for 12h;

Reference： [1]Location in patent: experimental part Santra, Santimukul; Kaittanis, Charalambos; Perez, J. Manuel [Langmuir, 2010, vol. 26, # 8, p. 5364 - 5373]
[2]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - US2016/256402, 2016, A1 Location in patent: Paragraph 0062; 0063
[3]Caubere,P.; Madelmont,J.-C. [Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1972, vol. 275, p. 1305 - 1308]
[4]Akiyama, Naoki; Goshima, Kenta; Hirota, Shun; Jatmika, Catur; Matsuo, Takashi; Wakabayashi, Kazumo [Dalton Transactions, 2020, vol. 49, # 33, p. 11618 - 11627]

5
[ 4753-59-7 ]
[ 603-35-0 ]
[ 6191-70-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	In toluene at 140℃; for 48h; Inert atmosphere;	6.3 A solution of triphenylphosphine (Sigma-Aldrich 99%, ReagentPlusu). (39.3 g, 150 mmol) and 4-bromobutyl acetate (Sigma-Aldrich) (26 mL, 180 mmol) in anhydrous toluene (300 mL) was heated under reflux for 36 hours under N2 in an oil-bath (140° C.). During the reflux, oil was precipitated out. The reaction mixture was cooled to room temperature. TLC (petroleum ether/EtOAc 7:3) analysis of the toluene solution showed that there was still triphenylphosphine (Rf: 0.8) left. The supernatant was decanted into another round-bottomed flask and concentrated down to the approximate volume of 30 mL. The solution was heated under reflux again for another 12 hours. The supernatant was decanted. The portions of oil were combined together, dissolved in water (500 mL) and extracted with EtOAc (2×500 mL). The combined organic layers were back-extracted with water (150 mL). Two lots of aqueous layers were combined, evaporated under reduced pressure. The resulting residue was co-evaporated with acetonitrile (2×100 mL) to give 78.4 g, 95% yield of a pale yellow oil. NMR indicates that the product was pure, and was used for the next step reaction without further purification. TLC: Rf: 0.0 (petroleum ether/EtOAc 7:3). 1H NMR (400 MHz, CDCl3): δ 1.63-1.73 (m, 2H, CH2), 1.94 (s, 3H, 2x CH3), 2.06-2.16 (m, 2H, CH2), 3.97-4.05 (m, 2H, CH2P), 4.11 (t, J=6.0, 2H, CH2O), 7.69-7.95 (m, 15H, Ph). 31P NMR (162 MHz, CDCl3): 25.9 ppm. Mass spec details: LC-MS (Electrospray positive): (Mt) 377.
95%	In toluene at 140℃; for 48h; Inert atmosphere;	4.3 Step 3:A solution of triphenylphosphine (Sigma-Aldrich 99%, ReagentPlus). (39.3 g, 150 mmol) and 4-bromobutyl acetate (Sigma-Aldrich)(26 mL, 180 mmol) in anhydrous toluene (300 mL) is heated under reflux for 36 hours under N2 in an oil-bath (140° C.). During the reflux, oil is precipitated out. The reaction mixture is cooled to room temperature. TLC (petroleum ether/EtOAc 7:3) analysis of the toluene solution showed that there is still triphenylphosphine (Rf: 0.8) left. The supernatant is decanted into another round-bottomed flask and concentrated down to the approximate volume of 30 mL. The solution is heated under reflux again for another 12 hours. The supernatant is decanted. The portions of oil are combined together, dissolved in water (500 mL) and extracted with EtOAc (2×500 mL). The combined organic layers are back-extracted with water (150 mL). Two lots of aqueous layers are combined, evaporated under reduced pressure. The resulting residue is co-evaporated with acetonitrile (2×100 mL) to give 78.4 g, 95% yield of a pale yellow oil. NMR indicates that the product is pure, and is used for the next step reaction without further purification. (0195) TLC: Rf: 0.0 (petroleum ether/EtOAc 7:3). (0196) 1H NMR (400 MHz, CDCl3): δ 1.63-1.73 (m, 2H, CH2), 1.94 (s, 3H, 2×CH3), 2.06-2.16 (m, 2H, CH2), 3.97-4.05 (m, 2H, CH2P), 4.11 (t, J=6.0, 2H, CH2O), 7.69-7.95 (m, 15H, Ph). (0197) 31P NMR (162 MHz, CDCl3): 25.9 ppm. (0198) Mass spec details: LC-MS (Electrospray positive): (M+) 377.
93%	In acetonitrile for 12h; Inert atmosphere; Reflux;	(4-Acetoxybutyl)triphenylphosphonium bromide (1) A mixture of 15.66 g of 4-bromobutyl acetate (80 mmol) (which was prepared according to the reported procedures[14]) and 21 g of triphenylphosphine (80 mmol) in 100cm3of acetonitrile was refluxed for 12 h under nitrogen[15]. Then it was cooled to room temperature and acetonitrile was removed to obtain a colorless oil. 50 cm3of ether was added to the oil and frozen in the refrigerator for 2 h.The mixture was ground to obtain a white granular solid,which was filtered, washed with ether and ethyl acetate,respectively, and dried in vacuum to obtain a white powdery solid, 34.3 g with a yield of 93%. The product can be used directly in the next step without further purification.1H NMR (DMSO-d6): δ = 7.85-7.73 (m, 15H, Ar-H), 4.09(t, J = 7.1 Hz, 2H, -CH2O-), 3.64 (t, J = 7.2 Hz, 2H, -CH2-),2.24 (s, 3H, COCH3),1.69-1.73 (m, 2H, -CH2-), 1.18-1.20(m, 2H, -CH3) ppm; 13C NMR (DMSO-d6): δ = 165.86,135.29, 130.65, 122.42, 119.06, 60.14, 32.39, 20.89, 20.27,14.25 ppm.

93%	In acetonitrile Reflux;	[4-(Acetyloxy)butyl]triphenylphosphonium bromide (1) 4-Bromobutyl acetate (23.5 g, 0.12 mol) and PPh3 (30 g,0.12 mol) were added to 250 mL acetonitrile and refluxed overnight. Acetonitrile was distilled off under reduced pressureto obtain a pale yellow viscous oil. After 150 mL ether was added, the mixture was frozen for 1 h, to give a white solid, the solid was then filtered and washed with ethyl acetate and ether, respectively, to afford 1 as a white powder, 51.3 g, 93%.24 1H NMR (600 MHz, DMSO-d6, ppm): δ 7.85-7.73 (m, 15H), 4.13-4.06 (t, J = 7.1 Hz, 2H), 2.05-1.71 (s,3H), 1.71-1.53 (m, 2H), 1.19 (m, 4H). 13C NMR (151 MHz,DMSO-d6, ppm) δ 165.8, 147.6, 135.2, 134.0, 133.9, 130.6,122.4, 119.0, 118.4, 60.1, 32.3, 20.8, 20.2, 14.5.
	at 130℃;
	In toluene Reflux; Inert atmosphere;

Reference： [1]Current Patent Assignee: ILLUMINA INC - US2015/343410, 2015, A1 Location in patent: Paragraph 0258; 0259; 0260; 0261; 0262; 0263
[2]Current Patent Assignee: ILLUMINA INC - US9267173, 2016, B2 Location in patent: Page/Page column 31; 32
[3]Gao, Jiyu; Zhou, Jianjun; Chen, Taiping; Xiao, Yan; Li, Zicheng; Huang, Wencai [Monatshefte fur Chemie, 2021, vol. 152, # 5, p. 545 - 549]
[4]Zhou, Jianjun; Xiao, Yan; Chen, Taiping; Gao, Jiyu; Huang, Wencai; Li, Zicheng [Journal of Chemical Research, 2021, vol. 45, # 3-4, p. 310 - 314]
[5]Bergel'son,L.D. et al. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1964, p. 1359 - 1361][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1964, # 8, p. 1453 - 1456]
[6]Current Patent Assignee: ILLUMINA INC - US2019/352327, 2019, A1 Location in patent: Paragraph 0225

6
[ 110-87-2 ]
[ 4753-59-7 ]
[ 31608-22-7 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 231 - 235

7
[ 4753-59-7 ]
[ 116747-65-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With 18-crown-6 ether; bis(triphenyltin) selenide; cesium fluoride In acetonitrile at 36℃; for 2h;

Reference： [1]Harpp, David N.; Gingras, Marc [Journal of the American Chemical Society, 1988, vol. 110, # 23, p. 7737 - 7745]

8
[ 4753-59-7 ]
[ 134461-75-9 ]
[ 5845-41-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With caesium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	1.1 Example 1: General procedure for the synthesis of carbamate acyclic purine nucleoside analogues General procedure: Step (1): To a stirred mixture of a suitable purine (1 equiv.) and cesium carbonate (1.2 equiv.) in dry DMF (1.5 mL/mmol), 4-bromobutylacetate (1.2 equiv.) was added dropwise under azote atmosphere. The reaction mixturewas left at room temperature overnight. The solvent was then evaporated under reduced pressure and the residue was partitioned between DCM and water. The organic layer was extracted twice with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude was then purified by flash column chromatography (0-10% MeOH inDCM) to afford the expected compound. The following compounds are examples illustrating step (1):; 4-(6-aminourin-9-yl)butyl acetate was prepared from adenine (1.35 g, 10mmol). Yield: 2.12 g (85%) of the title compound as a white powder. 1H NMR(300 MHz, ODd3) 8.36 (5, 1 H), 7.80 (5, 1 H), 5.71 (bs, 2H), 4.24 (t, J = 7.2Hz, 2H), 4.10 (t, J= 6.4 Hz, 2H), 2.04 (5, 3H), 2.00-1.94 (m, 2H), 1.72-1.65 (m,2H).
52%	Stage #1: adenine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at -60 - 20℃; Inert atmosphere;
50%	With 18-crown-6 ether; potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 0 - 25℃; for 1h;

33%	With potassium carbonate In N,N-dimethyl-formamide at 140℃; for 16h;
	With potassium carbonate In N,N-dimethyl-formamide at 20℃;

Reference： [1]Current Patent Assignee: BCI PHARMA - WO2017/191297, 2017, A1 Location in patent: Page/Page column 97; 98
[2]Kai, Kenji; Fujii, Hiroki; Ikenaka, Rui; Akagawa, Mitsugu; Hayashi, Hideo [Chemical Communications, 2014, vol. 50, # 62, p. 8586 - 8589]
[3]Lazrek, H. B.; Taourirte, M.; Barascut, J. L.; Imbach, J. L. [Bulletin des Societes Chimiques Belges, 1996, vol. 105, # 7, p. 391 - 396]
[4]Rosenberg, Ivan; Holy, Antonin; Masojidkova, Milena [Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 11B, p. 2753 - 2777]
[5]Lougiakis, Nikolaos; Papapetropoulos, Andreas; Gikas, Evangelos; Toumpas, Spyridon; Efentakis, Panagiotis; Wedmann, Rudolf; Zoga, Anastasia; Zhou, Zhongmin; Iliodromitis, Efstathios K.; Skaltsounis, Alexios-Leandros; Filipovic, Milos R.; Pouli, Nicole; Marakos, Panagiotis; Andreadou, Ioanna [Journal of Medicinal Chemistry, 2016, vol. 59, # 5, p. 1776 - 1790]

9
[ 4753-59-7 ]
[ 2140-11-6 ]
Acetic acid 4-[9-((3aR,4R,6R,6aR)-6-hydroxymethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-6-oxo-6,9-dihydro-purin-1-yl]-butyl ester [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1996,vol. 61,p. S92 - S95

10
[ 4753-59-7 ]
[ 172468-38-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium azide In N,N-dimethyl-formamide at 90℃; for 4h;
95%	With sodium azide In dimethyl sulfoxide at 25℃; for 16h;
	With sodium azide at 95℃; for 4h;

	With sodium azide In water; <i>tert</i>-butyl alcohol for 16h; Heating;
	With sodium azide In N,N-dimethyl-formamide at 90 - 95℃;

Reference： [1]Moukha-Chafiq; Taha; Lazrek; Vasseur; Pannecouque; Witvrouw; De Clercq [Nucleosides, nucleotides and nucleic acids, 2001, vol. 20, # 10-11, p. 1811 - 1821]
[2]Carrington, Simon; Renault, Jacques; Tomasi, Sophie; Corbel, Jean-Charles; Uriac, Philippe; Blagbrough, Ian S. [Chemical Communications, 1999, # 14, p. 1341 - 1342]
[3]Lazrek; Taourirte; Oulih; Lebtoumi; Barascut; Imbach [Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1115 - 1118]
[4]Demko, Zachary P.; Sharpless, K. Barry [Organic Letters, 2001, vol. 3, # 25, p. 4091 - 4094]
[5]Location in patent: scheme or table Moustafa, Ahmed H.; El-Sayed, Hassan A.; Haikal, Abd El-Fattah Z.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2011, vol. 30, # 5, p. 340 - 352]

11
[ 6270-63-9 ]
[ 4753-59-7 ]
[ 208931-60-6 ]
[ 208931-54-8 ]

Reference： [1]Nucleosides and Nucleotides,1998,vol. 17,p. 875 - 893
[2]Nucleosides and Nucleotides,1998,vol. 17,p. 1489 - 1504

12
[ 35435-68-8 ]
[ 4753-59-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	With tetrabutylammomium bromide; (chloro-phenylthio-methylene)dimethylammonium chloride In dichloromethane at 20℃;
89%	With silica bromide In dichloromethane at 20℃; for 0.166667h;

Reference： [1]Gomez; Gellibert; Wagner; Mioskowski [Tetrahedron Letters, 2000, vol. 41, # 32, p. 6049 - 6052]
[2]Mohanazadeh, Farajollah; Sedrpoushan, Alireza; Zolfigol, Mohammad A.; Veisi, Hojat [Letters in Organic Chemistry, 2012, vol. 9, # 8, p. 598 - 603,6]

13
[ 4753-59-7 ]
[ 6974-78-3 ]
[ 302908-40-3 ]
4-(6-amino-8-bromo-purin-3-yl)-butan-1-ol [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,2000,vol. 65,p. 1109 - 1125

14
[ 4753-59-7 ]
[ 157023-34-2 ]
4-[(4-acetoxy-butylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 1261 - 1264
[2]Bioorganic and medicinal chemistry,2002,vol. 10,p. 1347 - 1359

15
[ 1006-94-6 ]
[ 4753-59-7 ]
[ 1064777-90-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 5-methoxylindole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Stage #2: 4-Bromobutyl acetate With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 0 - 20℃; for 2.16667h;	15 To DMF (30 ml) was added NaH (600 mg, 15.29 mmol), and then 5-methoxy indol (1.5 g, 10.19 mmol) was slowly added thereto at 0°C , and the mixture was reacted for 5 minutes, with maintaining the temperature. To the reactant was slowly added 4-bromobutyl acetate (1.90 ml, 13.25 mmol) and tetrabutylammonium iodide (10 mg) was directly added thereto, and title mixture was reacted for 10 minutes, and then further reacted at room temperature for 2 hours. The reactant was neutralized with ammonium chloride (6.0 ml), diluted with water (40 ml) and extracted three times with ethyl acetate (100 ml). Ethyl acetate was removed from the reactant and the residue was purified by column chromatography (hexane: ethyl acetate = 10:1) to obtain the desired compound (24) as green oil in a yield of 93% (2.5 g, 9.59 mmol).
	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h;

Reference： [1]Current Patent Assignee: GYEONGSANG NATIONAL UNIVERSITY - WO2008/117935, 2008, A1 Location in patent: Page/Page column 49; 50
[2]Velu, Sadanandan E.; Cristofoli, Walter A.; Garcia, Gabriel J.; Brouillette, Christie G.; Pierson, Milton C.; Luan, Chi-Hao; DeLucas, Lawrence J.; Brouillette, Wayne J. [Journal of Medicinal Chemistry, 2003, vol. 46, # 15, p. 3371 - 3381]

16
[ 4753-59-7 ]
[ 6146-52-7 ]
[ 578725-92-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 5-nitroindole With sodium hydride In N,N-dimethyl-formamide at 20℃; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 20℃;

Reference： [1]Velu, Sadanandan E.; Cristofoli, Walter A.; Garcia, Gabriel J.; Brouillette, Christie G.; Pierson, Milton C.; Luan, Chi-Hao; DeLucas, Lawrence J.; Brouillette, Wayne J. [Journal of Medicinal Chemistry, 2003, vol. 46, # 15, p. 3371 - 3381]

17
[ 629-05-0 ]
[ 4753-59-7 ]
[ 107217-60-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(l) iodide; [(ν³-allyl)PdCl]2; 1,3-di(adamantan-1-yl)-1H-imidazol-3-ium chloride In diethyl ether; N,N-dimethyl-formamide at 45℃; for 16h;

Reference： [1]Eckhardt, Matthias; Fu, Gregory C. [Journal of the American Chemical Society, 2003, vol. 125, # 45, p. 13642 - 13643]

18
[ 10297-06-0 ]
[ 4753-59-7 ]
acetic acid 10-chlorodec-5-ynyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With copper(l) iodide; [(ν³-allyl)PdCl]2; 1,3-di(adamantan-1-yl)-1H-imidazol-3-ium chloride In diethyl ether; N,N-dimethyl-formamide at 45℃; for 16h;

Reference： [1]Eckhardt, Matthias; Fu, Gregory C. [Journal of the American Chemical Society, 2003, vol. 125, # 45, p. 13642 - 13643]

19
[ 4753-59-7 ]
[ 133338-58-6 ]
[ 579486-76-3 ]
9-(4-acetoxybutyl)-2-(3,4-dichlorobenzylamino)-6-oxopurine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 25% 2: 62%	With potassium carbonate In N,N-dimethyl-formamide at 45℃; for 18h;
1: 25% 2: 62%	With potassium carbonate In DMF (N,N-dimethyl-formamide) at 45℃; for 48h;	6 Potassium carbonate (400 mg, 2.9 mmol) and 4-bromobutyl acetate (520 mg, 2.67 mmol) were added to a solution of 2-(3,4-dichlorobenzylamino)-6-oxopurine (Nucl. Acids Res. 1990, 18, 7381-7387) (750 mg, 2.42 mmol) in DMF (20 ml). After stirring for 2 days at 45° C., the cooled mixture was poured into water (80 ml), and the solution was extracted with CHCl3 (4×50 ml). The organic layer was washed with water (100 ml) and brine (100 ml) and dried over magnesium sulfate. The filtrate was concentrated in vacuo, and the residue was chromatographed on a silica gel column. Elution with 2% MeOH in CHCl3 gave the 7-isomer 7 (255 mg, 25%), and elution with 2.5% gave the 9-isomer (640 mg, 62%). 1H NMR (DMSO-d6): δ1.50 (m, 2H, CH2), 1.80 (m, 2H, CH2), 1.97 (s, 3H, CH3CO), 3.94 (t, 2H, CH2), 4.15 (t, 2H, CH2N), 4.45 (d, 2H, CH2Ar), 6.60 (t, 1H, NH), 7.30 (d, 1H, Ar-H), 7.56 (m, 2H Ar-H), 7.90 (s, 1H, C8-H and 10.86 (s, 1H, NH).

Reference： [1]Wright, George E.; Brown, Neal C.; Xu, Wei-Chu; Long, Zheng-Yu; Zhi, Chengxin; Gambino, Joseph J.; Barnes, Marjorie H.; Butler, Michelle M. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 3, p. 729 - 732]
[2]Current Patent Assignee: ACURX PHARMACEUTICALS INC - US2004/14773, 2004, A1 Location in patent: Page/Page column 10; 14

20
[ 16494-36-3 ]
[ 4753-59-7 ]
acetic acid 4-(5-methylthiophene-2-sulfinyloxy)butyl ester [ No CAS ]
acetic acid 4-(5-methylthiophene-2-sulfonyl)butyl ester [ No CAS ]

Reference： [1]Organic Letters,2005,vol. 7,p. 1223 - 1225

21
[ 4753-59-7 ]
[ 105-53-3 ]
2-(4-acetoxy-but-1-yl)-malonic acid diethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate In acetonitrile for 36h; Heating;
76%	Stage #1: 4-Bromobutyl acetate; diethyl malonate In acetonitrile at 20℃; for 0.0333333h; Reflux; Stage #2: With potassium carbonate In acetonitrile for 36h; Reflux;
76%	With potassium carbonate In acetonitrile at 20℃; for 36h; Reflux;	Synthesis of 2-(4-Acetoxy-butyl)-malonic acid diethyl ester (3) Synthesis of 2-(4-Acetoxy-butyl)-malonic acid diethyl ester (3) (0064) Compound 3 was prepared by following a previously reported method. {Santra, 2004 6} Briefly, diethyl malonate 1 (10 g, 62.5 mmol), 4-bromobutyl acetate 2 (15.84 g, 81.3 mmol) were placed in a round bottom flask containing acetonitrile (120 mL) and stirred for 2 min at room temperature. Then to this, we added potassium carbonate (34.5 g, 250.1 mmol) and refluxed for 36 h. Next, the mixture was filtered and the filtrate was concentrated to obtain a yellow liquid. This was extracted with ethyl acetate, and washed with water. The organic layers were combined and dried over Na2SO4, and purified by column chromatography using 4% ethyl acetate in petroleum ether as the eluent. (0065) Yield: 13.02 g (76%). bp: 250° C. 1H NMR (300 MHz, CDCl3, δ ppm, J Hz): 1.28 (t, 6H, J=7.6), 1.38 (m, 2H), 1.62 (q, 2H, J=7.2), 1.98 (q, 2H, J=7.7), 2.05 (s, 3H), 3.34 (t, 1H, J=7.7), 4.09 (t, 2H, J=6.6), 4.22 (q, 4H, J=7.2). 13C NMR (75 MHz, CDCl3, δ ppm): 14.06, 20.79, 23.74, 28.25, 28.25, 51.84, 61.27, 63.89, 169.31, 171.11. IR (CHCl3): 2982, 1728, 1463, 1367, 1233, 1151, 1029, and 860 cm-1.

With potassium carbonate In ethyl acetate; acetonitrile; Petroleum ether

Materials Synthesis of 2-(4-Acetoxy-butyl)-malonic acid diethyl ester (3): Compound 3 was prepared by following a previously reported method. {Santra, 2004 #6} Briefly, diethyl malonate 1 (10 g, 62.5 mmol). 4-bromobutyl acetate 2 (15.84 g, 81.3 mmol) were placed in a round bottom flask containing acetonitrile (120 mL) and stirred for 2 min at room temperature. Then to this, we added potassium carbonate (34.5 g, 250.1 mmol) and refluxed for 36 h. Next, the mixture was filtered and the filtrate was concentrated to obtain a yellow liquid. This was extracted with ethyl acetate, and washed with water. The organic layers were combined and dried over Na2SO4, and purified by column chromatography using 4% ethyl acetate in petroleum ether as the eluent. Yield: 13.02 g (76%). bp: 250° C. 1H NMR (300 MHz, CDCl3, δ ppm, J Hz): 1.28 (t, 6H, J=7.6), 1.38 (m, 2H), 1.62 (q, 2H, J=7.2), 1.98 (q, 2H, J=7.7), 2.05 (s, 3H), 3.34 (t, 1H, J=7.7), 4.09 (t, 2H, J=6.6), 4.22 (q, 4H, J=7.2). 13C NMR (75 MHz, CDCl3, δ ppm): 14.06, 20.79, 23.74, 28.25, 28.25, 51.84, 61.27, 63.89, 169.31, 171.11. IR (CHCl3): 2982, 1728, 1463, 1367, 1233, 1151, 1029, and 860 cm-1.

Reference： [1]Santra, Santimukul; Kumar, Anil [Chemical Communications, 2004, # 18, p. 2126 - 2127]
[2]Location in patent: experimental part Santra, Santimukul; Kaittanis, Charalambos; Perez, J. Manuel [Langmuir, 2010, vol. 26, # 8, p. 5364 - 5373]
[3]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - US2016/256402, 2016, A1 Location in patent: Paragraph 0064; 0065
[4]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - US8372944, 2013, B1 Location in patent: Page/Page column

22
[ 4753-59-7 ]
[ 13552-21-1 ]
[ 663623-47-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In diethyl ether at 0 - 20℃; for 3 - 18h;	PREPARATION 10. (2-Hydroxybutylamino)-acetic acid ter-butyl ester To a stirred solution of 1-amino-2-butanol (4.69 g, 5.26 mmol) in anhydrous diethyl ether (100 ml) was added triethylamine (1.88 [ML,] 13.49 mmol), followed by the drop wise addition of 1-bromo-t-butyl acetate (4.23 [ML,] 13.49 mmol) in diethyl ether (25 [ML).] The mixture was stirred at [0°C] for 3 hours, then warmed to room temperature and stirred for 18 hours. The mixture was washed with water (50 ml) and extracted with diethyl ether (2 x 50 [ML).] The organic layer was washed with brine (30 [ML),] dried over magnesium sulfate, filtered, and the solvent removed upon evaporation under reduced pressure to give the intermediate compound (3.07 g, 89 %) as a colourless oil. [H-NMR] [(400MHZ,] CD30D) : [5=] 0.94 (t, 3H), 1.46 (2 x s, [11H),] 2.48 (dd, [1H),] 2.62 (dd, 1 H), 3.29 (d, 2H), 3.56 (m, [1 H).] LRMS [(APCI)] : m/z [M + H] [+] 204.

Reference： [1]Current Patent Assignee: BLAKEMORE; PFIZER INC - WO2004/16583, 2004, A1 Location in patent: Page 48-49

23
[ 722486-20-6 ]
[ 4753-59-7 ]
[ 722486-22-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate In ISOPROPYLAMIDE at 20℃; for 18h;	10.c 3-chloro-N- {5- [ (7-hydroxy-6-methoxyquinazolin-4-yl) amino] PYRIDIN-2-YL} BENZAMIDE (431 mg, 1. 01 MMOL), 4-bromobutyloxyacetate (294 mg, 1.5 mmol) and potassium carbonate (414 mg, 3.00 mmol) were dissolved in dimethylacetamide (15 ML) and stirred at ambient temperature for 18 hours. The reaction mixture was concentrated and water (10 ML) added. The resultant precipitate was removed by filtration, washed with water and dried under high vacuum. The solid was recrystallised from acetonitrile to afford 4-[4-({6-[(3- chlorobenzoyl) AMINO] PYRIDIN-3-YL} AMINO)-6-METHOXYQUINAZOHN-7-YL] OXY} BUTYL acetate (337 mg, 63 % yield): 'H-NMR (DMSO-D6) : 8.76 (s, 1H), 8.45 (s, 1H), 8.26 (m, 1H), 8.20 (d, 1H), 8.09 (s, 1H), 7.99 (d, 1H), 7.83 (s, 1H), 7.66 (d, 1H), 7.54 (t, 1H), 7.19 (s, 1H), 4.18 (t, 2H), 4. 08 (t, 2H), 3.95 (s, 3H), 2.00 (s, 3H), 1.84 (M, 2H), 1.75 (m, 2H) : MS (+VE ESI): 536 (M+H)+.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/58782, 2004, A1 Location in patent: Page 59

24
[ 4753-59-7 ]
[ 2140-11-6 ]
[ 206538-98-9 ]
Acetic acid 4-[9-((3aR,4R,6R,6aR)-6-hydroxymethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-6-oxo-6,9-dihydro-purin-1-yl]-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.12%; 80%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In DMF (N,N-dimethyl-formamide); at 20 - 65℃; for 2h;	This Example illustrates an intramolecular nucleophilic reaction to form a cyclic derivative of biological importance. A mixture of <strong>[2140-11-6]2',3'-O-isopropylideneinosine</strong> (3.08 g, 10.0 mmol) and 4-bromobutyl acetate (3 ml) in dimethylformamide (75 ml) containing DBU (2.4 ml) is heated to 65 C and then left at room temperature for 2 hours. The mixture is neutralized with concentrated hydrochloric acid and concentrated in vacuo. The residue is dissolved in chloroform, washed with water, dried over sodium sulfate and concentrated. The residue is chromatographed on a column of silica gel with CHCl3, CHCl3-EtOH (2%) to give a faster migrating, O-alkylated product (500 mg, 0.12%), 1H NMR (CDCl3) delta 1.35 (s, 3H, iPr), 1.63 (s, 3H, iPr), 1.80-1.86 (m, 2H, H3"), 1.94-1.97 (m, 2H, H2"), 2.03 (s, 3H, Oac), 3.76 (dd, 1H, H5', J4',5' = 2.0 Hz, J5',5" = 13.0 Hz), 3.96 (dd, 1H, H5", J4',5" = 0.6 Hz), 4.12 (pseudo t, 2H, H4", J3",4" = 6.2 Hz), 4.52-4.53 (m, 1H, H4'), 4.63 (pseudo t, 2H, H1", J1",2" = 5.2 Hz), 5.10 (dd, 1H, H3', J2',3' = 5.9 Hz; J3',4' = 0.98 Hz), 5.18 (pseodo t, 1H, H2'), 5.88 (d, 1H, H1', J1',2' = 4.9 Hz), 7.95, 8.48 ( two 1H singlets, H2, H8), and slower migrating N1-alkylated product (3.37 g, 80%), 1H NMR (CDCl3) delta 1.35 (s, 1H, iPr), 1.62 (s, 1H, iPr), 1.65-1.70 (m, 2H, H3"), 1.80-1.85 (m, 2H, H2"), 2.02 (s, 3H, OAc) , 3.77 (d, 1H, H5' , J5',5" = 12.6 Hz), 3.94 ( dd, 1H, H5", J4',5" = 1.7 Hz), 4.07 (pseudo t, 4H, H1",4"), 4.49 (d, 1H H4'), 5.05-5.10 (m, 2H, H2',3'), 5.86 (d, 1H, H1', J1',2' = 4.2 Hz), 7.90, 7.99 (two 1H singlets, H2, H8). The N1 alkylated product (422 mg, 1 mmol) is dissolved in pyridine (10 ml). Mesyl chloride (315 mul) is added and the mixture is kept at room temperature 20 minutes. Ethanol is added and the reaction mixture is concentrated in vacuo to give the desired mesylate in quantitative yield, 1H NMR (CDCl3) delta 1.37 (s, 3H, iPr), 1.60 (s, 3H, iPr), 1.68-1.71 (m, 2H. H3"), 1.83-1.88 (m, 2H, H2"), 2.02 (s, 3H, Oac), 2.92 (s, 3H, Ms), 4.06-4.11 (m, 4H, H1", H4"), 4.39-4.41 (m, 2H, H5', H5"), 4.47-4.49 (m, 1H, H4'), 5.07 (DD, 1H, H3', J2',3' = 6.4 Hz, J3',4' = 3.5 Hz), 5.32 (dd, 1H, H2', J1',2 = 2.2 Hz), 6.07 (d, 1H, H1'), 7.86, 7.98 (two 1H singlets, H2, H8).

Reference： [1]Patent: EP1469003,2004,A2 .Location in patent: Page 13; 30

25
[ 503614-56-0 ]
[ 4753-59-7 ]
1-(4-methoxyphenyl)-6-(4-(acetoxy)n-butyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With sodium hydride; In DMF (N,N-dimethyl-formamide); at 20℃;	1- (4-METHOXY-PHENYL)-7-OXO-4, 5,6, 7-TETRAHYDRO-LH-PYRAZOLO [3,4- c] pyridine-3-carboxylic acid ethyl ester (1.0 g, 3.17 mmol) was dissolved in N, N- DIMETHYLFORMAMIDE (40 rnL) and cooled to 0C. Sodium hydride (60%, 0.317 g, 7.93 mmol) was added followed by 4-bromobutyl acetate (0.918 mL, 6.34 mmol). The REACTION WAS STIRRED at rt overnight, quenched with IN hydrochloric acid (200 ML), EXTRACTED WITH ETHYL ACETATE (3X250 ML), WASHED WITH WATER (2X200 ML), WASHED WITH brine (1x200 mL), dried over MgSO4, concentrated, and purified by flash chromatography using 0-100% ethyl ACETATE/HEXANES GRADIENT AS THE ELUENT to afford 6-(4-acetoxy-butyl)-1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo [3,4- C] PYRIDINE-3-CARBOXYLIC acid ethyl ester (0.490 g, 36%). THE ester (0.490 g, 0.114 mmol) was dissolved in 5% NH3/ETHYLENE glycol (6 mL) in A pressure tube, heated at 80C for 2hr, cooled, quenched with water (100 ML), extracted with ethyl acetate (3X100 ML), washed with brine (1X100 ML), dried over MGSO4, concentrated, and purified by flash chromatography using 0-100% ethyl acetate gradient and 0-100% methanol/ethyl acetate gradient as the eluents to afford 0.295 g (72%): 1H NMR (CHC13) 8 7.45 (d,j=8. 8 Hz, 2H), 6.97 (d, j=9. 1 Hz, 2H), 6. 83 (s, 3H), 5.49 (s, 3H), 3.84 (s, 3H), 3.66 (t, j=6. 2 Hz, 2H), 3.51 (t, j=7. 3 Hz, 2H), 3.23 (t, j=6. 8 Hz, 2H), 1.72- 1.55 (m, 4H) ppm; Mass Spec 357.3 (M-H) -.
34.2%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃; for 16h;	Under room temperature, the 1 - (4-methoxyphenyl) - 7-oxo -4, 5, 6, 7-tetrahydro -1H-pyrazolo [3,4-c] pyridine-3-carboxylic acid ethyl ester (1.0 g, 3.2 millimoles) dissolved in DMF (40 ml) in. To the obtained sequentially in a mixture of butanol joins uncle potassium (0.7 g, 6.2 mmol), 4-bromo-n-butyl acetate (0.7 g, 3.6 mmol). The obtained reaction mixture at room temperature for 16 hours. To the resulting mixture of water quenching reaction (100 ml). The resulting mixture is extracted with ethyl acetate. The resulting organic phase is concentrated to obtain crude product under reduced pressure. The resulting crude product is purified by silica gel column chromatography (dichloromethane: methanol =200:1) to obtain 470 mg pale brown oily (yield: 34.2%).

Reference： [1]Patent: WO2004/83177,2004,A2 .Location in patent: Page 192-193
[2]Patent: CN105384739,2016,A .Location in patent: Paragraph 0552; 0553; 0554

26
[ 579486-85-4 ]
[ 4753-59-7 ]
[ 579486-83-2 ]
[ 579486-84-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 65% 2: 15%	With potassium carbonate In acetonitrile for 4h; Heating / reflux;	Potassium carbonate (1.5 g, 11 mmol) and 4-bromobutyl acetate (3 g, 15.4 mmol) were added to a solution of 2-(3-ethyl-4-methylphenylamino)-6-chloropurine (J. Med. Chem. 1988, 31, 1496-1501) (1.8 g, 6.26 mmol) in MeCN (80 mL). After 4 h at reflux, the solvent was removed in vacuo, and the residue was chromatographed on a silica gel column. Chloroform eluted the 9 isomer (1.65 g, 65%), and 5% MeOH in CHCl3 eluted the 7-isomer (378 mg, 15%). 7-isomer: 1H NMR (DMSO-d6): δ1.15 (t, 3H, CH3) 1.57 (m, 2H, CH2), 1.84 (m, 2H, CH2), 2.26 (s, 3H, CH3CO), 2.55 (q, 2H, CH2), 3.98 (t,2H, CH2), 4.35 (t, 2H, CH2N), 7.05 (d, 1H, ArH), 7.52 (d, 1H, ArH), 7.58 (dd, 1H, ArH), 8.56 (s, 1H, C8-H) and 9.55 (s, 1H, NH).

Reference： [1]Current Patent Assignee: ACURX PHARMACEUTICALS INC - US2004/14773, 2004, A1 Location in patent: Page/Page column 14

27
[ 1563-38-8 ]
[ 4753-59-7 ]
[ 884604-53-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 120h;	2.A Under a nitrogen atmosphere a solution of 5.0 grams (0.030 mole) of 7- hydroxybenzofuran (known compound), 6.5 grams (0.033 mole) of 4-bromobutyl acetate and 6.2 grams (0.045 mole) of potassium carbonate in 75 mL of DMF was stirred at ambient temperature during a five-day period. The reaction mixture was then stirred with 75 mL of water and saturated with solid sodium chloride. The mixture was extracted with three 50 mL portions of diethyl ether, and the combined extracts were washed with one 50 mL portion of water. The organic layer was then dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, yielding 8.0 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Reference： [1]Current Patent Assignee: FMC CORP - WO2006/47438, 2006, A2 Location in patent: Page/Page column 25

28
[ 186435-66-5 ]
[ 4753-59-7 ]
[ 478920-93-3 ]
[ 479069-83-5 ]

Yield	Reaction Conditions	Operation in experiment
34.5%	With potassium carbonate; In acetone;	Alternative Method B. A mixture of <strong>[186435-66-5]6-amino-2-methoxy-4-pyrimidone</strong> (30 g, 212.6 mmol), K2CO3 (44 g, 318 mmol), benzyltriethylammionium chloride (20 g, 88 mmol) and 4-bromobutyl acetate (60 g, 308 mmol) in acetone (800 ml) was heated at reflux overnight. After cooling to room temperature, the insoluble salts were filtered off and the solvent was removed. The residue was purified by chromatography on silica gel with CHCl3/MeOH (100:2-100:5) as eluent. After separation of 6-amino-2-methoxy-4-(4-acetoxybutyl)pyrimidine (22.8, yield 42%), 18.7 g (yield 34.5%) of 6-amino-2-methoxy-3-(4-acetoxybutyl)-4-pyrimidone was isolated as a white solid.

Reference： [1]Patent: US2003/181719,2003,A1

29
[ 186435-66-5 ]
CHCl₃/MeOH [ No CAS ]
[ 4753-59-7 ]
[ 479069-83-5 ]

Yield	Reaction Conditions	Operation in experiment
6.5 g (15%)	With lithium bromide; In N,N-dimethyl-formamide; mineral oil;	Method A. Sodium hydride (60% dispersion in mineral oil, 8.2 g, 205 mmol) was added to a mixture of <strong>[186435-66-5]6-amino-2-methoxy-4-pyrimidone</strong> (24.0 g, 170 mmol) in DMF at 0 C. After 0.5 hours, lithium bromide (19.2 g, 221 mmol) was added to the mixture and stirred for 0.5 hours at room temperature. The temperature was slowly increased to 70 C., and a solution of 4-bromobutyl acetate (50 g, 256 mmol) in DMF was added dropwise to the reaction mixture. The mixture was stirred at 70 C. for 3 hours. After cooling to room temperature, the solvent was removed in vacuo. The residue was purified by chromatography on silica gel using CHCl3/MeOH (1-5%) as eluent to give first 6.5 g (15%) of 6-amino-2-methoxy-4-(4-acetoxybutyl)pyrimidine as a white solid followed by 23.4 g (yield 54%) of 6-amino-2-methoxy-3-(4-acetoxybutyl)-4-pyrimidone as a white solid.

Reference： [1]Patent: US2003/181719,2003,A1

30
[ 186435-66-5 ]
[ 4753-59-7 ]
[ 478920-93-3 ]

Yield	Reaction Conditions	Operation in experiment
54%	With lithium bromide; In N,N-dimethyl-formamide;	6-Amino-2-methoxy-3-(4-acetoxybutyl)pyrimidin-4(3H)-one Sodium hydride (1.2 eq) was added to the mixture of <strong>[186435-66-5]6-amino-2-methoxy-4-pyrimidone</strong> (1 eq) in DMF at 0 C. Then lithium bromide (1.5 eq) was added to the mixture and stirred for 1 hour at room temperature. The mixture was added dropwise to a solution of 4-bromo-1-acetoxybutane (1.5 eq) in DMF at 50 C. Workup and chromatography gave 6-amino-2-methoxy-3-(4-acetoxybutyl)-4-pyrimidone (yield 54%) as a white solid. 300 MHz 1H NMR (DMSO-d6): delta 1.52 (m, 4H, 2*CH2), 2.0 (s, 3H, CH3CO) 3.76 (t, 2H, CH2O), 3.88 (s, 3H, CH3N),), 4.0 (t, 2H, CH2O), 4.82 (s, 1H, C5-H), 6.41 (s, 2H, NH2)ppm.

Reference： [1]Patent: US2003/114445,2003,A1

31
toluene ethanol [ No CAS ]
[ 4753-59-7 ]
[ 143782-20-1 ]
[ 154992-24-2 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; methanol; ethanol; dichloromethane; water;	EXAMPLE 4 4-(4,4-dimethyl-2,5-dioxo-3-(4-hydroxybutyl) 1-imidazolidinyl)-2-(trifluoromethyl)-benzonitrile 300 ml of dimethylformamide and 100 g of the product of Example 3 are introduced at 20/22 C. and the reaction medium is maintained under agitation at this temperature for approximately 5 minutes then 98.5 g of 4-bromobutyl acetate then 20 g of soda are added and the whole is maintained under agitation and under a nitrogen atmosphere at +20/+22 C. for approximately 22 hours. While maintaining agitation, at this temperature, 20 g of soda is added then over approximately 5 minutes 400 ml of methanol is added and the whole is maintained in this way for 1 hour. While leaving the temperature to rise, 500 ml of demineralized water at +20 C. is introduced under agitation, then the reaction medium is placed under agitation, 500 ml of demineralized water is added at +20 C. and the whole is maintained under agitation for 1 hour at 25/30 C., then cooled down under agitation to +0/+5 C., and maintained for 2 hours, followed by separating, washing with 4100 ml of demineralized water and drying. Purification is carried out by adding 696 ml of methylene chloride at 20/22 C. and washing with 3232 ml of demineralized water then drying, 5.8 g of supra black is added, the medium is maintained under agitation at 20+-2 C. for 2 hours followed by filtering and rinsing with 2116 ml of methylene chloride. After concentrating under agitation, 116 ml of denat. ethanol toluene is added at 20 C. then 174 ml of demineralized water is added. The reaction medium is cooled down under agitation to 20/22 C., maintained under agiatation for 2 hours at this temperature then cooled down to 0+-2 C. and maintained for 1 hour under these conditions, followed by separating, washing with 258 ml of ethanol with 50% water at 0/+2 C. and drying. In this way 111.5 g of expected product (white powder) is obtained. M.p.=102 C.

Reference： [1]Patent: US6107488,2000,A

32
[ 4753-59-7 ]
[ 907624-85-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With silver nitrate In acetonitrile at 20 - 70℃;	3.3a A solution of silver nitrate (7.87 g, 46.3 mmol) and 4-bromobutyl acetate (4.40 g, 22.6 mmol) in acetonitrile (100 mL) was stirred at room temperature overnight and then for an additional 1 hour at 70° C. The mixture was cooled to room temperature and then stirred with brine (150 mL) for 1 hour. The resulted mixture was filtered through Celite and washed with acetonitrile. The filtrate was concentrated and then extracted with ethyl acetate (50 mL×2). The combined organic extracts were washed with water and brine, dried over Na2SO4, filtered, concentrated and dried under vacuum to give the title compound as a yellow oil (3.58 g, 89% yield). The product, >95% purity from NMR analysis, was use in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 4.53 (t, J=6.2 Hz, 2H), 4.11 (t, J=6.1 Hz, 2H), 2.06 (s, 3H), 1.85-1.75 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 170.8, 72.5, 63.3, 24.8, 23.5, 20.7.

Reference： [1]Current Patent Assignee: NICOX S.A. - US2006/189603, 2006, A1 Location in patent: Page/Page column 32

33
[ 4753-59-7 ]
[ 871026-06-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-Chloro-5H-pyrrolo[3,2-d]pyrimidine With caesium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 0.25h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 20℃; for 30h;	139.i (i) Production of 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)butyl acetate To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (0.768 g) in N,N-dimethylformamide (10 mL) was added cesium carbonate (2.01 g) under ice-cooling, and the reaction mixture was stirred while warming to room temperature for 15 min. 4-Bromobutyl acetate (1.26 g) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 30 hrs. The reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (80 mL), and extracted with ethyl acetate (100 mL*3) The organic layer was washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=95/5 → 0/100). The object fraction was concentrated under reduced pressure and dried to give the title compound (1.084 g) as a colorless transparent oil. 1H-NMR (CDCl3) δ 1.636-1.730 (2H, m), 1.874-1.971 (2H, m), 2.047 (3H, s), 4.098 (2H, t, J= 6.3 Hz), 4.512 (2H, t, J= 6.3 Hz), 6.718 (1H, d, J= 3.3 Hz), 7.482 (1H, d, J= 3.3 Hz), 8.690 (1H, s).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1752457, 2007, A1 Location in patent: Page/Page column 181

34
[ 4753-59-7 ]
[ 79250-47-8 ]
methyl 2-(4-acetoxybutoxy)-5-(allyloxy)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In acetone for 12h; Reflux;
71%	With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide for 12h;
15%	Stage #1: 5-allyloxy-2-hydroxy-benzoic acid methyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Stage #2: 4-Bromobutyl acetate With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide; mineral oil at 25℃; for 12h;	methyl 2-(4-acetoxybutoxy)-5-(allyloxy)benzoate To a solution of sodium hydride (60% dispersion in oil) (144 mg, 3.6 mmol) in anhydrous DMF (3 mL) was added at 0 °C, Compound 3 (0.37 g, 1 .8 mmol) in anhydrous DMF (3 mL). After stirring for 1 h at 0 °C, tetrabutyl ammonium iodide (266 mg, 0.72 mmol) and 4-bromobutyl acetate (2.7 mL, 2.0 mmol) were added and the reaction mixture was stirred for a further 12 h at 25 °C. The reaction was stopped with the addition of saturated aqueous ammonium chloride (5 mL). Ethyl acetate (lOmI) was added and the organic layer was washed with water (5 x 15 mL), brine (15 mL) and dried over magnesium sulfate. Purification by silica gel flash column chromatography (cyclohexane : ethyl acetate; 8 : 2) afforded 4 as colourless oil (87 mg, 15%). 1H NMR (CDCI3) ö 7.35 (d, J= 3.2 Hz, 1H), 7.03 (dd, J= 8.7, 3.2 Hz, 1H), 6.90 (d, J= 8.7 Hz, 1H), 6.10-5.99 (m, 1H), 5.45-5.38 (m, 1H), 5.32-5.27 (m, 1H), 4.54-4.50 (m, 2H), 4.15 (t, J=6.0 Hz, 2H), 4.02 (t, J = 6.0 Hz, 2H), 3.89 (5, 3H), 2.06 (5, 3H), 1.90-1.85 (m, 4H); HRMS (ESI): [M+H] calcd. for C17H2306 323.1489, found 323.1486.

Reference： [1]Alexander, M. Yvonne; Alexander, M. Yvonne; Gill, Daniel M.; Jones, Alan M.; L. Cornelio, Marinonio; Mahmoud, Ayman M.; R. Povinelli, Ana Paula; Shamir, Sabrina A.; Wilkinson, Fiona L.; Zazeri, Gabriel
[2]Raiber, Eun-Ang; Wilkinson, James A.; Manetti, Fabrizio; Botta, Maurizio; Deakin, Jon; Gallagher, John; Lyon, Malcolm; Ducki, Sylvie W. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6321 - 6325]
[3]Current Patent Assignee: MANCHESTER METROPOLITAN UNIVERSITY - WO2017/42557, 2017, A1 Location in patent: Page/Page column 62; 63

35
[ 4753-59-7 ]
[ 526-75-0 ]
[ 1045863-70-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 2,3-Dimethylphenol With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 4-Bromobutyl acetate In tetrahydrofuran at 20 - 35℃;	2.D.1.1 A 5 L, 3 -neck round bottom flask equipped with a mechanical stirrer and a thermocouple is charged with 2,3-dimethylphenol (144.0 g, 1.18 mol) followed by r-BuOK (1.0 M in THF, 1.65 L) with stirring at rt. The resulting solution is stirred for 30 min, and then 4-bromobutyl acetate (300.0 g, 1.54 mol) is added over 10 min, and the internal temperature rises to 35 °C. The solution is stirred overnight, water (500 mL) is added, and the mixture is transferred to a separatory funnel. The layers are separated, and the aqueous layer is extracted once with EtOAc (200 mL). The combined organics are washed with brine (150 mL) and evaporated giving 285 g (103%) of crude material as a yellow oil.The residue is dissolved in THF (1000 mL) and water (250 mL). LiOH-H2O (64.37 g, 1.53 mol) is added, and the mixture is rapidly stirred for 3 h at rt. The layers are separated, and the aqueous layer is extracted once with EtOAc (300 mL). The combined organics are washed with water (200 mL), and brine (200 mL) and evaporated to give the title compound (167.3 g, 73% yield) as a light yellow syrup.
	With potassium carbonate In DMA at 20 - 65℃;	2.D.1.2 A 5 L, three-necked round bottom flask equipped with an overhead stirrer and nitrogen inlet is charged with 2,3-dimethylphenol (125.0 g, 1.02 mol), powdered K2CO3 (212.13 g, 1.53 mol), and DMA (500 mL) at rt. Next, 4-bromobutyl acetate (238.75 g, 1.22 mol) is added at rt with stirring. The mixture is then heated to 65 0C (internal). The progress of the reaction is monitored by LC-MS. After 22 h, >95% conversion is noted.At this point, 2.0 M aq KOH (1.50 L) is added over a 15 min period to the reaction mixture at 65 0C. The progress of the reaction is monitored by LC-MS. After 15 min, -95% conversion is noted. After 1 h, complete conversion to the alcohol is noted, and after 1.5 h, heating is discontinued. After cooling to rt, the reaction mixture is diluted MTBE (1.75 L) with stirring. The mixture is transferred to a separatory funnel, and the bottom aq DMA layer is drained. The MTBE layer is then washed with water (3 x 500 mL) and half saturated brine (500 mL). The MTBE layer is then concentrated in vacuo to 194.8 g of a golden colored liquid.The crude product is purified by short path, high vacuum (1 Torr) distillation. One forerun fraction (2.90 g) is collected between 90-140 °C (oil bath: 170 0C). 4-(2,3- dimethylphenoxy)butan-l-ol (189.90 g, 96% yield) is collected between 140-142 0C (sand bath: 185 0C) as a light orange liquid.LCMS (Standard Method), of 4-(2,3-dimethylphenoxy)butyl acetate: 3.05 min, 259 (M+Na)+. LCMS (Standard Method), of 4-(2,3-dimethylphenoxy)butan-l -ol: 2.82 min, 195 (M+H)+. 1H NMR (300 MHz, CDCl3): δ 7.04 (t, J = 7.9 Hz, 2 H), 6.78 (d, J = 7.7 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 3.99 (t, J = 5.9 Hz, 2 H), 3.70 (t, J = 6.3 Hz, 2 H), 2.27 (s, 3 H), 2.15 (s, 3 H), 1.93-1.76 (m, 4 H), 1.64 (bs, I H).

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2008/97483, 2008, A2 Location in patent: Page/Page column 22-23
[2]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2008/97483, 2008, A2 Location in patent: Page/Page column 23-24

36
[ 4753-59-7 ]
[ 124-38-9 ]
[ 26976-70-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 4-Bromobutyl acetate With chloro-trimethyl-silane; iodine; ethylene dibromide; lithium chloride; zinc In tetrahydrofuran Inert atmosphere; Stage #2: carbon dioxide With [Ni(PCy₃)2]2(N₂) In tetrahydrofuran; toluene at 0℃; Inert atmosphere; Stage #3: With hydrogenchloride In tetrahydrofuran; water; ethyl acetate; toluene

Reference： [1]Yeung, Charles S.; Dong, Vy M. [Journal of the American Chemical Society, 2008, vol. 130, # 25, p. 7826 - 7827]

37
[ 4649-09-6 ]
[ 4753-59-7 ]
[ 324570-72-1 ]

Yield	Reaction Conditions	Operation in experiment
93%		A solution of 7-azaindole-3-carboxaldehyde (4.19 g, 28 mmol) in dry N,N dimehylformamide (50 ml) was added dropwise, keeping the temperature between 5-10 C., to a stirring suspension of 60% sodium hydride (oil dispersion) (1.2 g, 30 mmol) in dry DMF (65 ml) under nitrogen atmosphere. After addition was completed, stirring was continued at the same temperature for 30 min., then a solution of 4-bromobutylacetate (6.16 g, 31 mmol) in dry N,N-dimethylformamide (15 ml) was added dropwise, and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 137 h, then water (100 ml) was added, and the mixture extracted with dichloromethane (2100 ml). The organic phase was washed with water (3100 ml), dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduce pressure to give an oil (6.8 g, 93%) which was used without further purification.

Reference： [1]Patent: US7060822,2006,B1 .Location in patent: Page/Page column 127-129

38
[ 889675-13-2 ]
[ 4753-59-7 ]
[ 936625-90-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: tert-butyl ({3-[amino(oxo)acetyl]-2-methyl-1H-indol-4-yl}oxy)acetate With sodium hydride In N,N-dimethyl-formamide for 0.416667h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide for 15h; Stage #3: With ammonium chloride In water; N,N-dimethyl-formamide	17Z EXAMPLE 17Z[00718] [1-(4-Acetoxy-butyl)-3-aminooxalyl-2-methyl-1 H-indol-4-yloxy]-acetic acid te/t-butyl ester. To a solution of indole (250 mg, 0.75 mmol) in DMF ( 3.8 mL) was added NaH (60% dispersion in mineral oil, 36 mg, 0.90 mmol). 4-Bromobutylacetate (0.12 mL, 0.83 mmol) was added after 25 min., and the reaction was quenched after 15 h. with saturated aq NH4CI (10 mL). The solution was extracted with EtOAc (0.1 L) and washed 3 x 20 mL H2O, 20 mL saturated aq NaCl, dried over Na2SO4, filtered and concentrated in vacuo to give a brown oil. The oil was chromatographed over silica gel (12 g column, 0 to 80 % EtOAc in heptane, over 40 min.) to give a mixture of starting indole (30 mg, 12 %) and desired acetate (0.23 g, 70%) as a yellow solid. Rf = 0.29 (25:75 heptane / EtOAc); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.11 - 7.16 (m, J=8.1 , 8.1 Hz, 1 H) 6.96 (d, J=7.9 Hz, 1 H) 6.54 (d, J=7.8 Hz, 1 H) 4.60 (s, 2 H) 4.08 - 4.14 (m, 4 H) 2.59 (s, 3 H) 2.05 (s, 3 H) 1.81 - 1.90 (m, 2 H) 1.72 (dd, J=8.8, 6.1 Hz, 2 H) 1.47 (s, 9 H).

Reference： [1]Current Patent Assignee: AMGEN INC - WO2007/56279, 2007, A2 Location in patent: Page/Page column 284

39
[ 4753-59-7 ]
[ 4027-54-7 ]
[ 1392445-94-1 ]
[ 1392445-90-7 ]

Reference： [1]Russian Chemical Bulletin,2011,vol. 60,p. 2396 - 2400,5
Izvestiya Akademi Nauk, Seriya Khimicheskaya,2011,p. 2349 - 2353,5

40
[ 4753-59-7 ]
[ 4027-54-7 ]
[ 1392445-87-2 ]
[ 1392445-88-3 ]

Reference： [1]Russian Chemical Bulletin,2011,vol. 60,p. 2396 - 2400,5
Izvestiya Akademi Nauk, Seriya Khimicheskaya,2011,p. 2349 - 2353,5

41
[ 312-73-2 ]
[ 4753-59-7 ]
[ 1429923-33-0 ]

Reference： [1]Russian Journal of Organic Chemistry,2013,vol. 49,p. 417 - 420
Zh. Org. Khim.,2013,vol. 49,p. 429 - 432,4

42
[ 906652-90-2 ]
[ 4753-59-7 ]
[ 1572233-04-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4-(4-chlorophenyl)-6-oxo-2-(pyridin-2-yl)-1,6-dihydropyridine-5-carbonitrile With potassium carbonate In N,N-dimethyl-formamide for 1h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide Reflux;	4.2.2 General procedure for glycosylation and alkylation General procedure: The 2-ONN derivatives 1a-c (0.010mol) were stirred with potassium carbonate (1.38g, 0.010mol) in dry DMF (15mL) for 1h, followed by the addition of the appropriate peracetylated glycosyl bromide (0.011mol) or alkyl halide (0.010mol) in portions. Except for allyl and propargyl derivatives, the reaction mixture was stirred at room temperature overnight, filtered to remove insoluble materials, and then the solvent was evaporated under reduced pressure. For allyl and propargyl derivatives, the reaction mixture was refluxed for 5h after stirring overnight; and after cooling it was filtered, and the filtrate was poured into ice-water to give the crude product as a precipitate, which in turn was filtered off and dried. The crude product obtained in all cases was purified by recrystallization from 95% ethanol.

Reference： [1]Abou-Elkhair, Reham A.I.; Moustafa, Ahmed H.; Haikal, Abdelfattah Z.; Ibraheem, Ahmed M. [European Journal of Medicinal Chemistry, 2014, vol. 74, p. 388 - 397]

43
[ 4753-59-7 ]
[ 1572232-57-5 ]
[ 1572233-09-0 ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: 4-(4-isopropylphenyl)-2-oxo-6-(2-thienyl)nicotinonitrile With potassium carbonate In N,N-dimethyl-formamide for 1h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide Reflux;	4.2.2 General procedure for glycosylation and alkylation General procedure: The 2-ONN derivatives 1a-c (0.010mol) were stirred with potassium carbonate (1.38g, 0.010mol) in dry DMF (15mL) for 1h, followed by the addition of the appropriate peracetylated glycosyl bromide (0.011mol) or alkyl halide (0.010mol) in portions. Except for allyl and propargyl derivatives, the reaction mixture was stirred at room temperature overnight, filtered to remove insoluble materials, and then the solvent was evaporated under reduced pressure. For allyl and propargyl derivatives, the reaction mixture was refluxed for 5h after stirring overnight; and after cooling it was filtered, and the filtrate was poured into ice-water to give the crude product as a precipitate, which in turn was filtered off and dried. The crude product obtained in all cases was purified by recrystallization from 95% ethanol.

Reference： [1]Abou-Elkhair, Reham A.I.; Moustafa, Ahmed H.; Haikal, Abdelfattah Z.; Ibraheem, Ahmed M. [European Journal of Medicinal Chemistry, 2014, vol. 74, p. 388 - 397]

44
[ 4753-59-7 ]
[ 79492-52-7 ]
[ 1572233-14-7 ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: 2-oxo-4,6-di(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile With potassium carbonate In N,N-dimethyl-formamide for 1h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide Reflux;	4.2.2 General procedure for glycosylation and alkylation General procedure: The 2-ONN derivatives 1a-c (0.010mol) were stirred with potassium carbonate (1.38g, 0.010mol) in dry DMF (15mL) for 1h, followed by the addition of the appropriate peracetylated glycosyl bromide (0.011mol) or alkyl halide (0.010mol) in portions. Except for allyl and propargyl derivatives, the reaction mixture was stirred at room temperature overnight, filtered to remove insoluble materials, and then the solvent was evaporated under reduced pressure. For allyl and propargyl derivatives, the reaction mixture was refluxed for 5h after stirring overnight; and after cooling it was filtered, and the filtrate was poured into ice-water to give the crude product as a precipitate, which in turn was filtered off and dried. The crude product obtained in all cases was purified by recrystallization from 95% ethanol.

Reference： [1]Abou-Elkhair, Reham A.I.; Moustafa, Ahmed H.; Haikal, Abdelfattah Z.; Ibraheem, Ahmed M. [European Journal of Medicinal Chemistry, 2014, vol. 74, p. 388 - 397]

45
[ 4753-59-7 ]
[ 143782-20-1 ]
[ 154992-24-2 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 14143 - 14148

46
[ 4753-59-7 ]
4-mesitylphthalazine-1(2H)-thione [ No CAS ]
4-(4-mesitylphthalazin-1-ylthio)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate In 1,2-dimethoxyethane at 25℃; for 1h; Reflux;	General procedure for synthesis of Se and S-alkyl compounds 14-18 General procedure: Method B: A mixture of 2 or 4 (0.01 mol) and K2CO3 (10 mmol) was stirred in anhydrous DMF (15 mL) for 1 h, then the appropriate alkyl halide viz. 4-bromobutylacetate, 2-acetoxyethoxymethyl bromide, 3-chloropropanol,1,3-dichloro-2-propanol and/or 2-(chloromethyl)oxirane (10 mmol) was added. The reaction mixture was stirred at 25° C overnight, and then the mixture was filtered off, and the solvent was then evaporated under reduced pressure. The solid product obtained was crystallized from appropriate solvent.

Reference： [1]El-Shamy, Ibrahim E.; Abdel-Mohsen; Alsheikh, Amer A.; Fouda, Moustafa M.G.; Al-Deyab, Salem S.; El-Hashash, Maher A. [Tetrahedron Letters, 2015, vol. 56, # 10, p. 1183 - 1188]

47
[ 4753-59-7 ]
4-mesitylphthalazine-1(2H)-selenone [ No CAS ]
4-(4-mesitylphthalazin-1-ylselanyl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate In 1,2-dimethoxyethane at 25℃; for 1h; Reflux;	General procedure for synthesis of Se and S-alkyl compounds 14-18 General procedure: A mixture of 2 or 4 (0.01 mol) and K2CO3 (10 mmol) was stirred inanhydrous DMF (15 mL) for 1 h, then the appropriate alkyl halide viz.4-bromobutylacetate, 2-acetoxyethoxymethyl bromide, 3-chloropropanol,1,3-dichloro-2-propanol and/or 2-(chloromethyl)oxirane (10 mmol) was added. Thereaction mixture was stirred at 25° C overnight and then heatedunder reflux for 4-7 h, the mixture was filtered off, and the solvent was thenevaporated under reduced pressure. The solid product obtained was crystallizedfrom appropriate solvent.

Reference： [1]El-Shamy, Ibrahim E.; Abdel-Mohsen; Alsheikh, Amer A.; Fouda, Moustafa M.G.; Al-Deyab, Salem S.; El-Hashash, Maher A. [Tetrahedron Letters, 2015, vol. 56, # 10, p. 1183 - 1188]

48
[ 4753-59-7 ]
[ 56-53-1 ]
(E)-((hex-3-ene-3,4-diylbis(4,1-phenylene))bis(oxy))bis(butane-4,1-diyl) diacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With caesium carbonate In acetone at 60℃; for 48h;	2 4.2.3. Synthesis of compounds 3 and 5 General procedure: To the solution of (E)-4,40-(hex-3-ene-3,4-diyl)diphenol (2) (134 mg, 0.5 mmol) in acetone (20 mL) were added cesium carbonate (489 mg, 1.5 mmol) and 2-bromoethyl acetate (116 mL, 1.05 mmol) or 4-bromobutyl acetate (152 mL, 1.05 mmol). The mixture was stirred at 60 °C for 48 h, concentrated in vacuo and dissolved in ethyl acetate (50 mL). Solution was washed with 10% citric acid (250 mL) and brine (150 mL). Organic phase was dried over Na2SO4 and concentrated under reduced pressure. Crude product was then purified by column chromatography with dichloromethane/methanol (40:1) as an eluent to afford compound 3 or 5. 4.2.3.2 (E)-((Hex-3-ene-3,4-diylbis(4,1-phenylene))bis(oxy))bis(butane-4,1-diyl) diacetate (5) Yield: 213 mg (86%); white solid; IR (ATR) ν 2982, 2953, 2929, 2869, 1732, 1608, 1531, 1472, 1364, 1241, 1178, 1060, 1034, 949, 841, 810 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.79 (t, 6H, J = 7.4 Hz, 2 * CH3), 1.83-1.95 (m, 8H, 4 * CH2), 2.08 (s, 6H, 2 * CH3), 2.15 (q, 4H, J = 7.4 Hz, 2 * CH2), 4.04 (t, 4H, J = 6.0 Hz, 2 * CH2), 4.18 (t, 4H, J = 6.0 Hz, 2 * CH2), 6.88-6.93 (m, 4H, 4 * Ar-H), 7.11-7.15 (m, 4H, 4 * Ar-H) ppm; 13C NMR (101 MHz, CDCl3) δ 13.43 (2C), 21.03 (2C), 25.45 (2C), 25.98 (2C), 28.59 (2C), 64.21 (2C), 67.16 (2C), 113.89 (4C), 129.74 (4C), 135.06 (2C), 138.72 (2C), 157.32 (2C), 171.26 (2C) ppm. HRMS m/z for C30H40O6 ([M + H+]+): calcd 497.2903; 497.2895 found. Elemental analysis calculated (%) for C30H40O6: C 72.55, H 8.12. Found: C: 72.28, H 8.28.

Reference： [1]Hodnik, Žiga; Tomašič, Tihomir; Smodiš, Domen; D'Amore, Claudio; Mašič, Lucija Peterlin; Fiorucci, Stefano; Kikelj, Danijel [European Journal of Medicinal Chemistry, 2015, vol. 103, p. 551 - 562]

49
[ 4753-59-7 ]
4-cyano-2-(meta-methoxyphenyl)pyrrole [ No CAS ]
4-(2-(4-cyano-1H-pyrrol-2-yl)-4-methoxyphenyl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With lithium carbonate; palladium(II) bromide In N,N-dimethyl acetamide at 90℃; for 24h; regioselective reaction;

Reference： [1]Wiest, Johannes M.; Pöthig, Alexander; Bach, Thorsten [Organic Letters, 2016, vol. 18, # 4, p. 852 - 855]

50
[ 4753-59-7 ]
(S)-tert-butyl (1-(4-((2,4-difluorobenzyl)carbamoyl)-2-(4-(difluoromethoxy)-3-hydroxyphenyl)oxazol-5-yl)ethyl)carbamate [ No CAS ]
(S)-4-(5-(5-(1-((tert-butoxycarbonyl)amino)ethyl)-4-((2,4-difluorobenzyl)carbamoyl)oxazol-2-yl)-2-(difluoromethoxy)phenoxy)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 4.5h;	117.1 Step 1: (S) -4- (5- (5- (1- ( (tert-Butoxycarbonyl) amino) ethyl) -4- ( (2, 4-difluorobenzyl) carbamoyl) oxazol-2-yl) -2- (difluoromethoxy) phenoxy) butyl acetate Step 1: (S) -4- (5- (5- (1- ( (tert-Butoxycarbonyl) amino) ethyl) -4- ( (2, 4-difluorobenzyl) carbamoyl) oxazol-2-yl) -2- (difluoromethoxy) phenoxy) butyl acetate[1837]To N, N-dimethylformamide (20 mL) were added (S) -tert-butyl (1- (4- ( (2, 4-difluorobenzyl) carbamoyl) -2- (4- (difluoromethoxy) -3-hydroxyphenyl) oxazol-5-yl) ethyl) carbamate (1.30 g, 2.4 mmol) , potassium carbonate (0.65 g, 4.7 mmol) and 4-bromobutyl acetate (0.40 mL, 3.0 mmol) . The mixture was stirred at 60 for 4.5 hours. To the mixture was added water (30 mL) and the resulting mixture was extracted with ethyl acetate (50 mL × 3) . The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (PE/EtOAc (v/v) 5/1) to give the title compound as a white solid (1.50 g, 95) .[1838]1H NMR (400 MHz, CDCl3) : δ ppm 7.59 -7.56 (m, 2H) , 7.45 -7.39 (m, 1H) , 7.23 (d, J 8.1 Hz, 1H) , 6.89 -6.84 (m, 2H) , 6.61 (t, JF-H 74.5 Hz, 1H) , 5.34 -5.29 (m, 1H) , 4.70 -4.60 (m, 2H) , 4.18 -4.13 (m, 6H) , 2.05 (s, 3H) , 1.96 -1.93 (m, 2H) , 1.89 -1.83 (m, 2H) , 1.53 (t, J 7.0 Hz, 3H) , 1.43 (s, 9H) and MS-ESI: 654.2 [M+H]+.

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2015/161830, 2015, A1 Location in patent: Paragraph 00660

51
[ 14003-34-0 ]
[ 4753-59-7 ]
2-(4-acetoxybutyloxy)-3-methylquinoxaline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 3-methyl-2-oxo-1,2-dihydroquinoxaline With potassium carbonate In N,N-dimethyl-formamide for 1h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 20℃; for 12h;	General procedure for alkylation General procedure: In separate experiments, a mixture of 1a (10 mmol) and potassium carbonate (11 mmol) in dry DMF (15 mL) was stirred for 1 h, and halide (glucosyl bromide, galactosyl bromide, lactosyl bromide, 4-bromobutylacetate, 2-acetoxyethoxymethyl bromide,or 3-chloropropanol (11 mmol)) was added portion-wise to the well-stirred reaction mixture. Stirring was continued overnight at room temperature. The solvent was evaporated, and the residue was washed with water, and treated with ethanol. The obtained precipitate was collected by filtration and recrystallized from ethanol. Similar experiments were carried out with 1b.

Reference： [1]El-Sayed, Hassan A.; Said, Said A.; Moustafa, Ahmed H.; Baraka, Mohamed M.; Abdel-Kader, Rimaa T. [Nucleosides, nucleotides and nucleic acids, 2016, vol. 35, # 1, p. 16 - 31]

52
[ 58773-29-8 ]
[ 4753-59-7 ]
2-(4-acetoxybutylsulfanyl)-3-methylquinoxaline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 3-methyl-1,2-dihydroquinoxaline-2-thione With potassium carbonate In N,N-dimethyl-formamide for 1h; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 20℃; for 12h;	General procedure for alkylation General procedure: In separate experiments, a mixture of 1a (10 mmol) and potassium carbonate (11 mmol) in dry DMF (15 mL) was stirred for 1 h, and halide (glucosyl bromide, galactosyl bromide, lactosyl bromide, 4-bromobutylacetate, 2-acetoxyethoxymethyl bromide,or 3-chloropropanol (11 mmol)) was added portion-wise to the well-stirred reaction mixture. Stirring was continued overnight at room temperature. The solvent was evaporated, and the residue was washed with water, and treated with ethanol. The obtained precipitate was collected by filtration and recrystallized from ethanol. Similar experiments were carried out with 1b.

Reference： [1]El-Sayed, Hassan A.; Said, Said A.; Moustafa, Ahmed H.; Baraka, Mohamed M.; Abdel-Kader, Rimaa T. [Nucleosides, nucleotides and nucleic acids, 2016, vol. 35, # 1, p. 16 - 31]

53
[ 5004-45-5 ]
[ 4753-59-7 ]
4-(1-oxo-4-phenylphthalazin-2(1H)-yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate In N,N-dimethyl-formamide for 2h; Reflux;
98%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h;

Reference： [1]Moustafa, Ahmed H.; El-Sayed, Hassan A.; Abd El-Hady, Rasha A.; Haikal, Abdelfattah Z.; El-Hashash, Maher [Journal of Heterocyclic Chemistry, 2016, vol. 53, # 3, p. 789 - 799]
[2]Mahmoud, Naglaa F. H.; Elsayed, Galal A. [Journal of Heterocyclic Chemistry, 2020, vol. 57, # 4, p. 1845 - 1862]

54
[ 4753-59-7 ]
[ 7440-66-6 ]
[ 737797-42-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: zinc at 20℃; for 0.0833333h; Glovebox; Inert atmosphere; Stage #2: 4-Bromobutyl acetate at 80℃; for 16h; Glovebox; Inert atmosphere;
	With iodine In N,N-dimethyl acetamide at 80℃; Schlenk technique; Inert atmosphere; Sealed tube;
	Stage #1: zinc With iodine In N,N-dimethyl acetamide Inert atmosphere; Schlenk technique; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 70℃; Inert atmosphere; Schlenk technique;

With chloro-trimethyl-silane; lithium chloride In tetrahydrofuran; ethylene dibromide at 25℃; Inert atmosphere; Schlenk technique;

Reference： [1]Price, Gregory A.; Bogdan, Andrew R.; Aguirre, Ana L.; Iwai, Toshiyuki; Djuric, Stevan W.; Organ, Michael G. [Catalysis science and technology, 2016, vol. 6, # 13, p. 4733 - 4742]
[2]Fulton, Tyler J.; Alley, Phebe L.; Rensch, Heather R.; Ackerman, Adriana M.; Berlin, Cameron B.; Krout, Michael R. [Journal of Organic Chemistry, 2018, vol. 83, # 23, p. 14723 - 14732]
[3]Paeth, Matthew; Tyndall, Sam B.; Chen, Liang-Yu; Hong, Jia-Cheng; Carson, William P.; Liu, Xingwu; Sun, Xiaodong; Liu, Jinjia; Yang, Kundi; Hale, Elizabeth M.; Tierney, David L.; Liu, Bin; Cao, Zhi; Cheng, Mu-Jeng; Goddard, William A.; Liu, Wei [Journal of the American Chemical Society, 2019, vol. 141, # 7, p. 3153 - 3159]
[4]Grokenberger, Lucie; Hammann, Jeffrey M.; Karaghiosoff, Konstantin; Knochel, Paul; Lutter, Ferdinand H.; Spieß, Philipp [Angewandte Chemie - International Edition, 2020, vol. 59, # 14, p. 5546 - 5550][Angew. Chem., 2020, vol. 132, p. 5591 - 5595,5]

55
[ 4753-59-7 ]
[ 14482-89-4 ]
4-(1-oxo-2,3,4,5-tetrahydroazepino[4,3-b]indol-6(1H)-yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With tetrabutylammomium bromide; sodium hydroxide In dichloromethane at 20℃; for 48h;	5.1.4.1 6-(2-Phenylethyl)-3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one (12b) General procedure: TBAB (0.443g, 1.38mmol), phenethyl bromide (0.65mL, 2.50mmol) and 5.0mL of 25% m/m NaOH solution were added to a solution of 10a (0.25g, 1.275mmol) in 15mL of dry DCM. The mixture was stirred at rt for 48h, and then diluted with 20mL of DCM and 20mL of water. The collected organic phase was washed twice with 20mL of brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with ethyl acetate, to afford 12b as pale brown solid (0.270g, 70% yield).

Reference： [1]de Candia, Modesto; Zaetta, Giorgia; Denora, Nunzio; Tricarico, Domenico; Majellaro, Maria; Cellamare, Saverio; Altomare, Cosimo D. [European Journal of Medicinal Chemistry, 2017, vol. 125, p. 288 - 298]

56
[ 4753-59-7 ]
[ 6375-47-9 ]
4,4'-(5-acetamido-2-methoxyphenylazanediyl)bis(butane-4,1-diyl)diacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57 g	With sodium hydrogencarbonate; at 105℃;	<strong>[6375-47-9]3'-amino-4'-methoxyacetanilide</strong> (18.0 g, 0.1 mol),A stirred mixture of 4-bromobutyl acetate (48.8 g, 0.25 mol), 1-methyl-2-pyrrolidinone (50 ml), and sodium bicarbonate (55.2 g, 0.66 mol) was placed in a 105 C. oil bath Heat overnight, allow to cool, then pour into water (500 ml). After stirring for 30 minutes, the separated oil was extracted with dichloromethane (150 ml), the organic layer was dried (MgSO 4) and evaporated to give a thick brown oil (57.0 g). The oil is used as is without further purification (purity 95%).

Reference： [1]Patent: JP2015/519445,2015,A .Location in patent: Paragraph 0070; 0071

57
[ 4753-59-7 ]
[ 6375-47-9 ]
4,4′-(5-acetamido-2-methoxyphenylazanediyl)bis(butanediacetate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In 1-methyl-pyrrolidin-2-one; at 105℃;	A stirred mixture of <strong>[6375-47-9]3'-amino-4'-methoxyacetanilide</strong> (18.0 g, 0.1 mol), 4-bromobutyl acetate (48.8 g, 0.25 mol), 1-methyl-2-pyrrolidinone (50 ml) and sodium bicarbonate (55.2 g, 0.66 mol) is heated in an oil bath at 105 C. overnight, allowed to cool and then poured into water (500 ml), After stirring for 30 minutes, the oil that separates is extracted with dichloromethane (150 ml), the organic layer is dried (MgSO4) and evaporated to give a thick brown oil (57.0 g). The oil is used directly without further purification (95% purity).
57 g	With sodium hydrogencarbonate; In 1-methyl-pyrrolidin-2-one; at 105℃;	A stirred mixture of 23 3?-amino-4?-methoxyacetanilide (18.0 g, 0.1 mol), 24 4-bromobutyl acetate (48.8 g, 0.25 mol), 25 1-methyl-2-pyrrolidinone (50 ml) and 26 sodium bicarbonate (55.2 g, 0.66 mol) is heated in an oil bath at 105 C. overnight, allowed to cool and then poured into water (500 ml). After stirring for 30 minutes, the oil that separates is extracted with dichloromethane (150 ml), the organic layer is dried (MgSO4) and evaporated to give a thick brown 27 oil (57.0 g). The oil is used directly without further purification (95% purity).

Reference： [1]Patent: US9494808,2016,B2 .Location in patent: Page/Page column 31; 32
[2]Patent: US10106686,2018,B2 .Location in patent: Page/Page column 45-46; 47

58
[ 4753-59-7 ]
[ 70500-72-0 ]
C₁₅H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70 g	With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 85℃; for 4h;	<strong>[70500-72-0]7-hydroxy-1H-quinolin-2-one</strong> (60 g) was dissolved in dimethylformamide (600 mL). Afterdissolution, potassium carbonate (77 g) and 4-bromobutylacetate (compound of formula IX, 88 g) was added to the reaction mixture and the resulting solution was heated to 80-85 C and maintained for four hours at same temperature. After the reaction was complete, the reaction mass was cooled to room temperature. Water (600 mL) was added to the reaction mass and extracted with ethyl acetate (3 x 300 mL). The solvent was distilled completely under vacuum.Isopropyl ether (100 mL) was added and the reaction mixture was maintained for one hour at room temperature. The solution was filtered and the product washed with water (100 mL) and dried at 50 C to obtain 7-(4-acetylbutoxy)- 1H-quinolin-2-one (70 g).1H NMR (CDCl3): 1.83-1.92 (m, 4H); 2.07 (s, 3H); 4.08-4.18 (m, 4H); 6.55 (d, J=9.3Hz, 1H); 6.79-6.86(m, 2H); 7.43 (d, 1H, J=8.7Hz); 7.73(d, 1H, J=9.3Hz), Mass: 276 (M+1)

Reference： [1]Patent: WO2017/25987,2017,A1 .Location in patent: Page/Page column 21

59
[ 4753-59-7 ]
[ 131088-00-1 ]
4-(2-chloro-4-formyl-3-hydroxyphenoxy)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.2%	With 18-crown-6 ether; potassium hydrogencarbonate; sodium iodide In acetone at 70℃; for 96h;	2.1 6-(2-chloro-4-formyl-3-hydroxyphenoxy)butyl acetate, 60a In scintillation vial, a suspension of 3-chloro-2,4-dihydroxybenzaldehyde (0.5175 g, 3 mmol), KHCO3 (0.49 g, 4.9 mmol), NaI (0.45 g, 3 mmol), 18-crown-6 (0.132 g, 0.5 mmol) and methyl 6-bromobutanoate (0.585 g, 3.0 mmol) in acetone (5 ml) was heated and stirred for 4 days at 70° C. The reaction mixture was cooled to room temperature, acidified with HCl, aq. 1M and extracted with ethyl acetate (25 ml). Organic layer was washed with water (25 ml) and then with brine (25 ml). Organic layer was dried over MgSO4, concentrated and chromatographed to yield compound 60a (0.182 g, 0.64 mmol, 21.2%).

Reference： [1]Current Patent Assignee: IMMUNETARGET INC - US2017/182051, 2017, A1 Location in patent: Paragraph 0178

60
[ 4753-59-7 ]
[ 16097-62-4 ]
4-[2-(methylsulfanyl)-6-(trifluoromethyl)pyrimidin-4-yloxy]butyl acetate [ No CAS ]
4-[2-(methylsulfanyl)-4-(trifluoromethyl)-6-oxopyrimidin-1(6H)-yl]butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 69% 2: 21 %Spectr.	With potassium carbonate In acetonitrile for 12h; Reflux;	Alkylation of 2-(methylsulfanyl)-6-(polyfluoro-alkyl)pyrimidin-4(3H)-ones 1a-1c with 4-bromo-butyl acetate (2). General procedure: a. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 1 mmol of compound 1a-1c in 10 mL of acetonitrile, and the mixture was refluxed for 12 h with stirring. The mix-ture was cooled and filtered, the filtrate was concentrated, and the products (compounds 3a-3c and 4c) were isolated by column chromatography using chloro-form as eluent. b. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 210 mg (1 mmol) of compound 1a in 10 mL of 1,4-dioxane, and the mixture was refluxed for 12 h with stirring. The mixture was cooled and filtered, the filtrate was concentrated, and the product, compound 4a, was purified by column chromatog-raphy using hexane-ethyl acetate (5 : 1) as eluent. 4-[2-(Methylsulfanyl)-6-(trifluoromethyl)pyrimi-din-4-yloxy]butyl acetate (3a). Yield 69%, yellowish oily material. IR spectrum (ATR), ν, cm -1 : 1741 (C=O), 1559, 1591 (C=C, C=N), 1238-1282 (C-F). 1 H NMR spectrum (CDCl 3 ), δ, ppm: 1.82 m [4H, (CH 2 ) 2 ], 2.06 s (3H, Ac), 2.57 s (3H, SMe), 4.13 t (2H, OCH 2 , J = 6.3 Hz), 4.45 t (2H, OCH 2 , J = 6.2 Hz), 6.69 s (1H, 5-H). 19 F NMR spectrum (CDCl 3 ): δ F 91.16 ppm, s (CF 3 ). Mass spectrum, m/z (I rel , %): 324 (11.7) [M] + , 211 (24.7) [M - C 4 H 6 OC=OCH 3 ] + , 210 (42.3) [M - C 4 H 7 OC=OCH 3 ] + , 141 (11.1) [M - CF 3 - C 4 H 7 OC=OCH 3 ] + , 115 (49.2) [C 4 H 8 OC=OCH 3 ] + , 73 (17.4) [CH 2 OC=OCH 3 ] + , 71 (17.1) [OC 4 H 7 ] + , 55 (68.9) [C 4 H 7 ] + , 54 (11.5) [C 4 H 6 ] + , 43 (99.9) [C=OCH 3 ] + . Found, %: C 44.71; H 4.61; N 8.44. C 12 H 15 F 3 N 2 O 3 S. Calculated, %: C 44.44; H 4.66; N 8.64. M 324.32.
1: 63% 2: 23 %Spectr.	With potassium carbonate In 1,4-dioxane for 12h; Reflux;	Alkylation of 2-(methylsulfanyl)-6-(polyfluoro-alkyl)pyrimidin-4(3H)-ones 1a-1c with 4-bromo-butyl acetate (2). General procedure: a. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 1 mmol of compound 1a-1c in 10 mL of acetonitrile, and the mixture was refluxed for 12 h with stirring. The mix-ture was cooled and filtered, the filtrate was concentrated, and the products (compounds 3a-3c and 4c) were isolated by column chromatography using chloro-form as eluent. b. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 210 mg (1 mmol) of compound 1a in 10 mL of 1,4-dioxane, and the mixture was refluxed for 12 h with stirring. The mixture was cooled and filtered, the filtrate was concentrated, and the product, compound 4a, was purified by column chromatog-raphy using hexane-ethyl acetate (5 : 1) as eluent.

Reference： [1]Khudina; Burgart, Ya. V.; Saloutin [Russian Journal of Organic Chemistry, 2017, vol. 53, # 10, p. 1556 - 1563][Zh. Org. Khim., 2017, vol. 53, # 10, p. 1528 - 1535,8]
[2]Khudina; Burgart, Ya. V.; Saloutin [Russian Journal of Organic Chemistry, 2017, vol. 53, # 10, p. 1556 - 1563][Zh. Org. Khim., 2017, vol. 53, # 10, p. 1528 - 1535,8]

61
[ 4753-59-7 ]
6-difluoromethyl-2-methylsulfanylpyrimidin-4(3H)-one [ No CAS ]
4-[6-(difluoromethyl)-2-(methylsulfanyl)pyrimidin-4-yloxy]butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate In acetonitrile for 12h; Reflux;	Alkylation of 2-(methylsulfanyl)-6-(polyfluoro-alkyl)pyrimidin-4(3H)-ones 1a-1c with 4-bromo-butyl acetate (2). General procedure: a. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 1 mmol of compound 1a-1c in 10 mL of acetonitrile, and the mixture was refluxed for 12 h with stirring. The mix-ture was cooled and filtered, the filtrate was concentrated, and the products (compounds 3a-3c and 4c) were isolated by column chromatography using chloro-form as eluent. b. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 210 mg (1 mmol) of compound 1a in 10 mL of 1,4-dioxane, and the mixture was refluxed for 12 h with stirring. The mixture was cooled and filtered, the filtrate was concentrated, and the product, compound 4a, was purified by column chromatog-raphy using hexane-ethyl acetate (5 : 1) as eluent.

Reference： [1]Khudina; Burgart, Ya. V.; Saloutin [Russian Journal of Organic Chemistry, 2017, vol. 53, # 10, p. 1556 - 1563][Zh. Org. Khim., 2017, vol. 53, # 10, p. 1528 - 1535,8]

62
[ 4753-59-7 ]
6-heptafluoropropyl-2-methylsulfanylpyrimidin-4(3H)-one [ No CAS ]
4-[6-(heptafluoropropyl)-2-(methylsulfanyl)pyrimidin-4-yloxy]butyl acetate [ No CAS ]
4-[4-(heptafluoropropyl)-2-(methylsulfanyl)-6-oxopyrimidin-1(6H)-yl]butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 69% 2: 18%	With potassium carbonate In acetonitrile for 12h; Reflux;	Alkylation of 2-(methylsulfanyl)-6-(polyfluoro-alkyl)pyrimidin-4(3H)-ones 1a-1c with 4-bromo-butyl acetate (2). General procedure: a. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 1 mmol of compound 1a-1c in 10 mL of acetonitrile, and the mixture was refluxed for 12 h with stirring. The mix-ture was cooled and filtered, the filtrate was concentrated, and the products (compounds 3a-3c and 4c) were isolated by column chromatography using chloro-form as eluent. b. 4-Bromobutyl acetate (2), 195 mg (1 mmol), and potassium carbonate, 166 mg (1.2 mmol), were added to a solution of 210 mg (1 mmol) of compound 1a in 10 mL of 1,4-dioxane, and the mixture was refluxed for 12 h with stirring. The mixture was cooled and filtered, the filtrate was concentrated, and the product, compound 4a, was purified by column chromatog-raphy using hexane-ethyl acetate (5 : 1) as eluent.

Reference： [1]Khudina; Burgart, Ya. V.; Saloutin [Russian Journal of Organic Chemistry, 2017, vol. 53, # 10, p. 1556 - 1563][Zh. Org. Khim., 2017, vol. 53, # 10, p. 1528 - 1535,8]

63
[ 4753-59-7 ]
1-benzyl-4-phenyl-1,4-diazepane-5,7-dione [ No CAS ]
4-(1-benzyl-5,7-dioxo-4-phenyl-1,4-diazepan-6-yl)n-butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: 1-benzyl-4-phenyl-1,4-diazepane-5,7-dione With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 4-Bromobutyl acetate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 2h;	1.1-4 4- (1-Benzyl-5,7-dioxo-4-phenyl-1,4-diazepin-6-yl) n-butylLe acetate (SMY-1169) To a solution of 1-benzyl-4-phenyl-1,4-diazepin-5,7-dione (400 mg, 1.4 mmol) obtained in Synthesis Example 1-3 in DMF / THF (5 + 5 mL)NaH (70.7 mg, 1.8 mmol) was slowly added.After stirring at room temperature for 30 minutes, n-butyl 4-bromoacetate (255.6 μL, 1.8 mmol) was added to the mixture.The reaction mixture was stirred at room temperature for 2 hours.The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (10 mL × 3).The combined organic layers were washed with water (20 mL × 1) and brine (20 mL × 1), dried over Na 2 SO 4, filtered and concentrated in vacuo.The obtained residue was purified by MPLC (hexane / ethyl acetate = 3: 1 to 0: 1) to obtain the objective compound as a colorless oil (315.1 mg, 57%),The starting material was recovered (135.6 mg, 34%).
57%	Stage #1: 1-benzyl-4-phenyl-1,4-diazepane-5,7-dione With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate at 20℃; for 2h; Inert atmosphere;	4-(1-benzyl-5,7-dioxo-4-phenyl-1,4-diazepan-6-yl)butyl acetate(2a-OAc) To a solution of dione (9a: 400 mg, 1.4 mmol) inDMF/THF (5 + 5 mL) was slowly added NaH (70.7 mg, 1.8 mmol).After being stirred for 30 min at room temperature, 4-bromobutylacetate (10: 255.6 mL, 1.8 mmol) was added to the mixture. Thereaction mixture was stirred for 2 h at room temperature. The reactionmixture was diluted with water (20 mL) and extracted withAcOEt (10 mL 3). The combined organic layers were washed withwater (20 mL 1) and brine (20 mL 1), dried over Na2SO4, filteredoff and concentrated in vacuo. The resultant residue waspurified by MPLC (hexane/ethyl acetate = 3:1 to 0:1) to give 2a-OAc (315.1 mg, 57% yield) as a colorless oil and recovered startingmaterial 9a (135.6 mg, 34% yield). 1H NMR (600 MHz, CDCl3) d7.32-7.25 (m, 7H), 7.20 (t, J = 7.2 Hz, 1H), 7.04-7.02 (m, 2H), 4.90(d, J = 15.0 Hz, 1H), 4.41 (d, J = 15.0 Hz, 1H), 4.42-4.19 (m, 1H), 4.07(t, J = 6.6 Hz, 2H), 4.02 (t, J = 6.6 Hz, 1H), 3.80-3.75 (m, 1H), 3.54-3.46 (m, 2H), 2.12-2.05 (m, 2H), 2.02 (s, 3H), 1.73-1.68 (m, 2H),1.47-1.42 (m, 2H); 13C NMR (150 MHz, CDCl3) d 170.9, 167.6,167.1, 142.2, 136.8, 129.0, 128.5, 127.9, 127.5, 126.8, 126.1, 64.2,51.0, 49.9, 49.7, 47.0, 28.6, 26.0, 24.2, 20.8; HRMS (ESI) m/z calcdfor C24H28N2NaO4 [M+Na]+: 431.1941 found 431.1906.

Reference： [1]Current Patent Assignee: KYOTO PREFECTURAL UNIVERSITY; TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM - JP2017/178811, 2017, A Location in patent: Paragraph 0185-0187; 0198-0200
[2]Ota, Yosuke; Miyamura, Shin; Araki, Misaho; Itoh, Yukihiro; Yasuda, Shusuke; Masuda, Mitsuharu; Taniguchi, Tomoyuki; Sowa, Yoshihiro; Sakai, Toshiyuki; Itami, Kenichiro; Yamaguchi, Junichiro; Suzuki, Takayoshi [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 3, p. 775 - 785]

64
[ 4753-59-7 ]
[ 10310-21-1 ]
[ 108437-69-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With caesium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	3 Example 3: Preparation of 2-iodo-2-chloro purine acyclic nucleoside analogue To a stirred suspension 2-amino-6-chloropurine (1.70 g, 10 mmol, 1equiv.) in DMF (25 mL), were added cesium carbonate (3.90 g, 12 mmol, 1.2equiv.) and 4-bromobutyl acetate (1 .74 mL, 12 mmol, 1 .2 equiv.) dropwise. The reaction mixture was stirred at room temperature overnight under azote atmosphere. The solvent was then removed under reduced pressure and the residue purified by flash column chromatography (0-10% MeOH in DCM) toprovide 4-(2-amino-6-chloro-purin-9-yl)butyl acetate (2.15 g, 76%) as a white powder.

Reference： [1]Current Patent Assignee: BCI PHARMA - WO2017/191297, 2017, A1 Location in patent: Page/Page column 107

65
[ 4753-59-7 ]
[ 75-31-0 ]
4-isopropylamino-1-acetoxyl butane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydrogencarbonate In acetonitrile at 5 - 20℃; for 5h;	5 Example 5: Preparation of4-isopropylamino- 1 -acetoxyl butane 39 g of 4-bromo-1-acetoxyl butane, 250 mL of acetonitrile and 100 g of sodium bicarbonate were added to a 500 mL four-neck flask and cooled to 5° C. by ice-water bath, 35.4 g of isopropyl amine was added dropwise, then the mixture was heated to 20° C. and reacted for 5 hours until the reaction was completed. Inorganic salts were removed by filtration, thefiltrate was concentrated to recover acetonitrile, 300 mL ofethyl acetate was added to the residue to recrystallize, and31.8 g of 4-isopropylamino- 1 -acetoxyl butane was obtained.The molar yield was 92%.1H-NMR data: (400 MHz, CDC13) ö: 4.02 (t, J=6.8Hz, 2H), 2.74 (m, 1H), 2.57 (t, J=7.2 Hz, 2H), 1.97 (s, 3H),1.62 (m, 2H), 1.49 (m, 2H), 0.99 (d, J=6.0 Hz, 6H).

Reference： [1]Current Patent Assignee: SEASONS BIOTECHNOLOGY; SHANGHAI SHIJI BIOLOG TECHNOLOGY; SHANGHAI SEASONS BIOTECHNOLOGY; SEASONS BIOTECHNOLOGY TAIZHOU - US2018/29973, 2018, A1 Location in patent: Paragraph 0051-0054; 0055; 0056; 0057; 0058; 0059; 0060-0065

66
[ 4753-59-7 ]
[ 100048-61-1 ]
C₁₇H₃₀O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium hydride In tetrahydrofuran	1 EXAMPLE 1: Bi-DOTA Complex-Loaded Dendritic Polymer Nanoparticles for X-ray Imaging and Treatment of Lung Cancer A new aliphatic HBPE polymer with sulfur pendants (HBPE-S polymer) for theeffective loading of bismuth complexes, potentially to achieve higher X-ray contrast wassynthesized. The synthetic scheme for the HBPE-S polymer is illustrated in Figure 1. Briefly, compounds 1, 2 (62.5 mol) and K2C03 (312.5 mol) were taken in acetonitrile and refluxed. The purified mono-thio-alkylated product 3 (40.0 mmol) was reacted with 4- bromobutyl acetate (48 mmol) in dry THF containing NaH (56 mmol) to produce thedialkylated compound 4 (76%). Comparing to previous work (Id.), the second acidic proton of diethylmalonate (1) was substituted with 2-chloroethyl ethyl sulfide (2) to get sulfur pendants in 4. The hydrolysis of 4 (19.2 mmol) was carried out in an aqueous methanol solution (MeOH:H20 = 5:1) containing NaOH (67.3 mmol) at 90°C, resulting in the final branched monomer 5 (7 1%) containing sulfur as pendants.

Reference： [1]Current Patent Assignee: STATE UNIVERSITY SYSTEM OF FLORIDA - WO2018/13927, 2018, A1 Location in patent: Page/Page column 28; 29

67
[ 4753-59-7 ]
3-(3’-adamantan-1-yl-4’-hydroxy-biphenyl-4-yl)acrylic acid methyl ester [ No CAS ]
3-[4’-(4-acetoxy-butoxy)-3’-adamantan-1-yl-biphenyl-4-yl]acrylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h;	15.1 Step 1 : 3-[4'-(4-Acetoxy-butoxy)-3'-adamantan-1-yl-biphenyl-4-yl]-acrylic acid methyl ester (BIO3). A mixture of 3-(3'-adamantan-1 -yl-4'-hydroxy-biphenyl-4-yl)-acrylic acid methyl ester (Example 9, Step 1 ) (100 mg, 0.26 mmol), 4-bromobutyl acetate (67.4 mg, 0.34 mmol), K2CO3(102 mg, 0.74 mmol) in 4.50 ml of DMF was heated at 80 °C for 2 h. K2C03was filtered, DMF evaporated and the residue was taken up with water. The mixture was diluted with ethyl acetate, washed with 1 M HCI, water and brine. The organic phase was dried and the solvent evaporated. Purification by flash chromatography (petroleum ether/ethyl acetate 80: 20) gave 98 mg (75 %) of product as white solid, m.p. 157 °C, Rf(petroleum ether/EtOAc 80:20) 0.50.1H-NMR (300 MHz, DMSO-d6) δ: 7.76-7.60 (4H, m); 7.56 (1 H, d, J =16.5 Hz); 7.48 (1 H, dd, J = 8.50, 2.14 Hz); 7.43 (1 H, d, J = 2.14 Hz); 6.95 (1 H, d, J = 8.50 Hz); 6.51 (1 H, d, J = 16.5 Hz); 4.84 (2H, s); 3.73 (3H, s); 4H missing due to the overlap with signal solvent; 2.20-1.98 (9H, m); 1.84-1.65 (6H, m); 1 .47 (7H, s).
75%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h;	11.A A) 3- [4' - (4-Acetoxy-butoxy) -3' -adamantan-1 -yl -biphenyl -4-yl ] - acrylic acid methyl ester A mixture of 3- (3 ' -adamantan-l-yl-4 ' - hydroxy-biphenyl-4-yl ) -acrylic acid methyl ester (100 mg, 0.26 mmol), 4-bromobutyl acetate (67.4 mg, 0.34 mmol), K2CO3 (102 mg, 0.74 mmol) in DMF (4.50 mL) was heated 2h at 80 °C. Then, K2CO3 was filtered, DMF evaporated and the residue was diluted with ethyl acetate and washed with 1M HC1, water and brine. The organic phase was dried over anhydrous Na2SC>4 and the solvent evaporated. Purification by flash chromatography (petroleum ether/ethyl acetate 80: 20) gave 98 mg (75 %) of product as white solid, m.p. 157 °C, Rf (petroleum ether/EtOAc 80:20) 0.50. 1H-NMR (300 MHz, DMSO-d6) d: 7.76-7.60 (4H, m) ; 7.56 (1H, d, J =16.5 Hz); 7.48 (1H, dd, J = 8.50, 2.14 Hz); 7.43 (1H, d, J = 2.14 Hz); 6.95 (1H, d, J = 8.50 Hz); 6.51 (1H, d, J = 16.5 Hz);4.84 (2H, s); 3.73 (3H, s); 4H missing due to the overlap with signal solvent; 2.20-1.98 (9H, m) ; 1.84-1.65 (6H, m) ; 1.47 (7H, s) .

Reference： [1]Current Patent Assignee: BIOGEM S C A R L - WO2018/60354, 2018, A1 Location in patent: Page/Page column 36
[2]Current Patent Assignee: SPECIAL PRODUCTS LINE - WO2020/178053, 2020, A1 Location in patent: Page/Page column 46-47

68
[ 6328-58-1 ]
[ 4753-59-7 ]
C₁₂H₁₈N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.3%	Stage #1: 6-methyl-2-methylsulfanyl-3H-pyrimidin-4-one; 4-Bromobutyl acetate With caesium carbonate In 1,4-dioxane; N,N-dimethyl-formamide for 1h; Reflux; Inert atmosphere; Stage #2: With 6,7,9,10,17,18-hexahydrodibenzo[b,h][1,4,7,10,13]pentaoxacyclopentadecine; tetrabutylammomium bromide; N-benzyl-N,N,N-triethylammonium chloride In 1,4-dioxane; N,N-dimethyl-formamide for 4h; Reflux;	1 In a nitrogen inert atmosphere,To 100 mL of a complex solvent (composed of an equal volume of 1,4-dioxane and DMF) in a reactor, 10 mmol of the compound of the above formula (I) was added,Add 10mmol alkylating agentBr(CH2)4OAc(4-Bromobutyl acetate)And 15 mmol of basic reagent cesium carbonate, and after heating under reflux for 1 hour with stirring, then adding 0.5 mmol of phase transfer catalyst benzyltriethylammonium chloride and 0.1 mmol of cocatalyst tetra-n-butylammonium bromide,Add 1 mmol of dibenzo-15-crown-5 auxiliaries under stirring until it is evenly mixed.The mixture was heated under reflux for 4 hours. After the reaction was completed, the resulting mixture was cooled.Cool to 0-15 °C, filter, concentrate the filtrate,Separation by silica gel column chromatography (the eluent used was a mixed solvent of n-hexane and ethyl acetate in a volume ratio of 5:1), and the eluent was collected and the elution solvent was removed under reduced pressure to obtain the target of the above formula (III). The compound has a yield of 96.3%.H PLC analysis showed a purity greater than 99%. Elemental analysis data confirmed the structure of the product.

Reference： [1]Current Patent Assignee: Chen Guofei - CN107915684, 2018, A Location in patent: Paragraph 0044; 0045; 0046; 0054; 0057; 0058; 0061; 0063;

69
[ 4753-59-7 ]
6‑(naphthalen‑2‑yl)‑2‑oxo‑4‑(p‑tolyl)‑1,2‑dihydropyridine‑3‑carbonitrile [ No CAS ]
4‑(3‑cyano‑6‑(naphthalen‑2‑yl)‑2‑oxo‑4‑(p‑tolyl)pyridin‑1(2H)‑yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate In dichloromethane at 150℃; for 0.133333h; Sealed tube; Microwave irradiation; Green chemistry; regiospecific reaction;	MW method General procedure: A 10 mL process vail was charged with amixture of 1a or /1b (1 mmol), peracetylated sugar (namely,peracetylated glucose/galactose or/ribose), 4-bromo butylacetate or/ 2-acetoxyethoxymethyl bromide (1.1 mmol), anddry CH2Cl2(5 mL), then (1.0 g) of silica gel (200-400 mesh)was added (In case of compounds 8a, b and 9a, b, pot. carbonate(2.1 mmol) was added). The vail was sealed, placedinto the cavity of the irradiated with microwave (Discoverby CEM, 2450 MHz, 300 W, 150 °C) for 5-8 min (Table 1).The residual product was chromatographed on silica gelusing CH2Cl2/MeOH (99:1) to give the desired product.

Reference： [1]Moustafa, Ahmed H.; Ahmed, Mohammed H. M. [Journal of the Iranian Chemical Society, 2018, vol. 15, # 9, p. 2107 - 2115]

70
[ 4753-59-7 ]
4‑(3‑methylthien‑2‑yl)‑6‑(naphthalen‑2‑yl)‑2‑oxo‑1,2‑dihydropyridine‑3‑carbonitrile [ No CAS ]
4‑(3‑cyano‑4‑(3‑methylthiophen‑2‑yl)‑6‑(naphthalene‑2‑yl)‑2‑oxopyridin‑1(2H)‑yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate In dichloromethane at 150℃; for 0.133333h; Sealed tube; Microwave irradiation; Green chemistry; regiospecific reaction;	MW method General procedure: A 10 mL process vail was charged with amixture of 1a or /1b (1 mmol), peracetylated sugar (namely,peracetylated glucose/galactose or/ribose), 4-bromo butylacetate or/ 2-acetoxyethoxymethyl bromide (1.1 mmol), anddry CH2Cl2(5 mL), then (1.0 g) of silica gel (200-400 mesh)was added (In case of compounds 8a, b and 9a, b, pot. carbonate(2.1 mmol) was added). The vail was sealed, placedinto the cavity of the irradiated with microwave (Discoverby CEM, 2450 MHz, 300 W, 150 °C) for 5-8 min (Table 1).The residual product was chromatographed on silica gelusing CH2Cl2/MeOH (99:1) to give the desired product.

Reference： [1]Moustafa, Ahmed H.; Ahmed, Mohammed H. M. [Journal of the Iranian Chemical Society, 2018, vol. 15, # 9, p. 2107 - 2115]

71
[ 4753-59-7 ]
[ 90-15-3 ]
4-(naphthalen-1-yloxy)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In acetone for 24h; Reflux;	9 4.1.2. Methyl 4-(naphthalen-1-yloxy)butanoate (11a) General procedure: To a stirred mixture of 1-naphthol (1.54g, 10.7mmol) and potassium carbonate (2.95g, 21.4mmol) in acetone (20mL) was added methyl 4-bromobutyrate (3.87g, 21.4mmol). The reaction mixture was refluxed for 24h then allowed to cool to room temperature, filtered and washed with acetone. The filtrate was evaporated under vacuum. The residue was purified by silica gel column chromatography (EtOAc/n-hexane=1:10) to afford compound 11a. Yield (2.96g, quantitative). 1H NMR (400MHz, CDCl3) δ 8.26-8.24 (1H, m, H-8), 7.82-7.78 (1H, m, H-5), 7.50-7.34 (4H, m, H-6, H-7, H-3, H-4), 6.79 (1H, d, J=7.5Hz, H-2), 4.19 (2H, t, J=6.6Hz, -OCH2-), 3.70 (3H, s, -COOCH3), 2.65 (2H, t, J=6.6Hz, -OCH2CH2CH2-), 2.27 (2H, q, J=6.6Hz, -OCH2CH2-).

Reference： [1]Hassan, Ahmed H.E.; Cho, Min Chang; Kim, Hye In; Yang, Ji Seul; Park, Kyung Tae; Hwang, Ji Young; Jang, Choon-Gon; Park, Ki Duk; Lee, Yong Sup [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 18, p. 5069 - 5078]

72
[ 109-99-9 ]
[ 506-96-7 ]
[ 57-13-6 ]
[ 4753-59-7 ]
[ 591-07-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 75.19% 2: 61.17%	Stage #1: tetrahydrofuran; Acetyl bromide; urea at 60℃; for 4h; Stage #2: With sodium carbonate In water at 20℃;	2 Test 2: This test is a preparation method of 4-halobutyl acetate, specifically according to the following steps: Urea was sequentially added to a three-necked flask equipped with a thermometer, a stirring, a reflux condenser, and a constant pressure dropping funnel.And tetrahydrofuran, the acetyl halide was added through a constant pressure dropping funnel under stirring, and the temperature was 60 ° C after the addition was completed.The reaction was stirred for 4 h under the conditions, naturally cooled to room temperature, distilled water was added, and then adjusted to pH 8 with an alkali solution, suction filtration, respectivelyObtaining a solid by-product and filtrate I, extracting the filtrate I three times with 20 mL of ethyl acetate, and adding anhydrous sodium sulfate to the acetic acidThe ester extract was dried, filtered to obtain a filtrate II, and the filtrate II was subjected to distillation under reduced pressure to give a pale yellow 4-bromobutyl group.Acetate, the yield is 75.19%;The reduced pressure distillation conditions is 74 °C -75 °C/12 mmHg; The acetyl halogen is acetyl bromide; The alkali solution is sodium carbonate aqueous solution; Said urea with tetrahydrofuran in a molar ratio of 1:15; Said urea with acetyl halogen in a molar ratio of 1:5; Said urea of the amount of substance with distilled water of volume ratio of 1 µM: 2 L From the above data, it can be confirmed that the 4-halobutyl acetate prepared in this test is 4-bromobutyl acetate. -; The solid by-product of this test is white powder after drying, and is subjected to infrared absorption spectrum test. After identification, it was determined to be acetylurea, and the yield of acetylurea was 61.17%.

Reference： [1]Current Patent Assignee: HEILONGJIANG UNIVERSITY - CN108484398, 2018, A Location in patent: Paragraph 0073-0080; 0087-0088; 0091

73
[ 4753-59-7 ]
4-(4-fluorophenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile [ No CAS ]
4-(3-cyano-4-(4-fluorophenyl)-2-oxo-6-(p-tolyl)pyridin-1(2H)-yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate In N,N-dimethyl-formamide for 20h; Reflux;	3.10. General Procedure for the Synthesis of Acyclic Nucleosides (4a,b, and 6a,b) General procedure: A mixture of 1a,b (10 mmol) with an appropriate acyclic sugar namely, 4-bromobutylacetate bromide and (2-acetoxyethoxy)methyl bromide and was added to dry DMF(20 mL) in the presence of anhydrous K2CO3 (11 mmol), the reaction mixture was heated under reflux for 20 hours and followed by TLC, cooling then poured onto ice water the formed precipitate was collected by filtration, and separated by silica gel chromatography (200-400 mesh) using CH2Cl2 /pot. ether 40/60 (in ratio 80: 20) as eluent.

Reference： [1]Ibrahim, Tarek S.; El-Sayed, Hassan A.; Khayat, Maan T.; Al-Mahmoudy, Amany M. M.; Moustafa, Ahmed H.; El-Deen, Ayat K. S.; Rostom, Sherif A. F.; Panda, Siva S. [Medicinal Chemistry, 2018, vol. 14, # 8, p. 791 - 808]

74
[ 4753-59-7 ]
[ 1240387-84-1 ]
4-(3-cyano-4-(3,4-dimethoxyphenyl)-2-oxo-6-(p-tolyl)pyridin-1(2H)-yl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium carbonate In N,N-dimethyl-formamide for 20h; Reflux;	3.10. General Procedure for the Synthesis of Acyclic Nucleosides (4a,b, and 6a,b) General procedure: A mixture of 1a,b (10 mmol) with an appropriate acyclic sugar namely, 4-bromobutylacetate bromide and (2-acetoxyethoxy)methyl bromide and was added to dry DMF(20 mL) in the presence of anhydrous K2CO3 (11 mmol), the reaction mixture was heated under reflux for 20 hours and followed by TLC, cooling then poured onto ice water the formed precipitate was collected by filtration, and separated by silica gel chromatography (200-400 mesh) using CH2Cl2 /pot. ether 40/60 (in ratio 80: 20) as eluent.

Reference： [1]Ibrahim, Tarek S.; El-Sayed, Hassan A.; Khayat, Maan T.; Al-Mahmoudy, Amany M. M.; Moustafa, Ahmed H.; El-Deen, Ayat K. S.; Rostom, Sherif A. F.; Panda, Siva S. [Medicinal Chemistry, 2018, vol. 14, # 8, p. 791 - 808]

75
[ 368-54-7 ]
[ 4753-59-7 ]
4-(4-acetoxybutoxy)-2-(4-acetoxybutylthio)-6-trifluoromethylpyrimidine [ No CAS ]
3-(4-acetoxybutyl)-2-(4-acetoxybutylthio)-6-trifluoromethylpyrimidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%; 19%	With potassium carbonate; In acetonitrile;Reflux;	General procedure: A. A mixture of thiouracil 1a-c (0.75 mmol), 4-bromobutyl acetate (0.29 g, 1.5 mmol), and K2CO3 (0.14 g, 1 mmol) in MeCN (10 mL) was refluxed for 4-10 h. The precipitate was filtered off , and the mother liquor was concentrated. The products were purified by column chromatography (products 2c and 3c were isolated using a 1 : 1 CHCl3-ethyl acetate mixture as the eluent; compounds 2a and 3a were isolated using a 5 : 1 CH2Cl2-ethyl acetate mixture; compounds 2b and 4b were isolated with a 5 : 1 CHCl3-ethyl acetate mixture).

Reference： [1]Russian Chemical Bulletin,2019,vol. 68,p. 1190 - 1195
Izv. Akad. Nauk, Ser. Khim.,2019,p. 1190 - 1195,6

76
[ 4753-59-7 ]
(5,6-diphenyl-pyrazin-2-yl)-isopropyl-amine [ No CAS ]
C₂₅H₂₉N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.9%	Stage #1: (5,6-diphenyl-pyrazin-2-yl)-isopropyl-amine With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide at 40℃; for 12h;	3 Example 3 The compound represented by formula (II) was prepared according to the method of Example 2. A 250 mL three-necked flask was placed in a stirrer, and anhydrous DMF (40 mL) was added, and a constant pressure dropping funnel, a low temperature thermometer, and a tee were connected. After adding a compound (17.3 mmol, 5 g) represented by formula (II), lowering the temperature to about 0 ° C, and replacing the system with nitrogen three times,Maintain the system at about 0 ° C and add sodium hydride (0.42g, 17.5mmol). After 30 minutes,A solution of 4-bromobutyl acetate (3.37 g, 17.3 mmol) in DMF was added dropwise. After the dropwise addition was completed, the temperature was slowly raised to 40 ° C for 12 hours. The reaction was monitored by TLC for completion. After stirring, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure at 45 ° C to obtain 8.1 g of a crude product. The crude product was passed through a column and concentrated to obtain 5.5 g of a solid with a yield of 78.9%.

Reference： [1]Current Patent Assignee: HUNAN HUATENG PHARMACEUTICAL CO LTD - CN110437077, 2019, A Location in patent: Paragraph 0081-0084

77
[ 4753-59-7 ]
[ 49823-14-5 ]
C₁₇H₂₃N₂O₂⁽¹⁺⁾*Br^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In toluene at 80℃; for 0.333333h; Microwave irradiation; Green chemistry;	3.2.1. General procedures for the synthesis of imidazolium halides (1-17)using the microwave method General procedure: The alkyl halides (1.1 eq) were added to a solution of 1-pentyl-1Himidazole(1 eq) in toluene. The solution was then treated with irradiationfor 20 min in a closed vessel at 80 °C using a CEM Microwave. Thecompletion of the reaction was indicated by the formation of an oil orsolid phase from the initially clear homogenous mixture composed ofN,N-pentylimidazole and the alkyl halide in toluene. The product waseither filtered or extracted, and then washed with ethyl acetate. TheIL/salt was then dried at reduced pressure.

Reference： [1]Ali, Imran; Almutairi, Saud M.; Alqurashy, Bakheet A.; Alrefaei, Abdulwahed F.; Hammouti, Belkheir; Manoharadas, Salim; Messali, Mouslim; Sahu, Pramod K.; Titi, Abderrahim; Touzani, Rachid [Journal of Molecular Liquids, 2020, vol. 315]

78
[ 178043-12-4 ]
[ 4753-59-7 ]
4-(2,6-dichloro-4-(3,3-dichloroallyloxy)phenoxy)-1-butanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol; 4-Bromobutyl acetate With potassium carbonate In acetonitrile Reflux; Stage #2: With sodium hydroxide In methanol; water at 20℃;	Add to 200mL round bottom flask25mmol2,6-dichloro-4-(3,3-dichloroallyloxy)phenol,Anhydrous potassium carbonate (50mmol),4-bromobutyl acetate (30mmol),Then add 100mL acetonitrile as solvent,Stir and heat to reflux,Stop the reaction after TLC detects the reaction is complete. The potassium carbonate was filtered off, the filtrate was concentrated under reduced pressure, and silica gel column chromatography was used to obtain a colorless oily product with a yield of 85%.Add 20mmol of the above intermediate to a 200mL round bottom flask,Then add 100mL methanol and 10mL water, stir at room temperature,Then NaOH (30 mmol) was added, and TLC detected until the reaction was complete.The reaction solution was concentrated under reduced pressure. After most of the methanol was spun out, the pH was adjusted to 5 with 2M HCl, then ethyl acetate was added to extract the organics, the organic phase was washed with saturated brine, and dried with anhydrous sodium sulfate.After removing the solvent, silica gel column chromatography gave a colorless oily product.The yield was 84%.

Reference： [1]Current Patent Assignee: UNIV CENTRAL CHINA NORMAL - CN111454204, 2020, A Location in patent: Paragraph 0073-0075

79
[ 4753-59-7 ]
[ 19768-54-8 ]
3-(4-acetoxybutyl)-1-pentyl-1H-imidazol-3-ium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In toluene at 100℃; for 0.333333h; Sealed tube; Microwave irradiation;	Microwave irradiation synthesis (1-16) General procedure: To a solution of 1-pentyl-1H-imidazole (1 eq.) in toluene, was added alkyl halides (1.1 eq) were exposed under irradiation for 20 min in closed vessel at 100° C. The completion of the reaction was marked by the separation of oil or solid from the initially obtained clear and homogenous mixture of 1-pentylimidazole and alkyl halide in toluene. Filtered or extracted the product and followed by washing with ethyl acetate. In each case, the IL/salt was finally dried at a reduced pressure

Reference： [1]Al Johani, Anas R.; Almutairi, Saud M.; El-Sayed, Wael S.; Sahu, Pramod K.; Sahu, Praveen K.; Messali, Mouslim [Asian Journal of Chemistry, 2020, vol. 32, # 8, p. 1972 - 1980]

80
[ 108-55-4 ]
[ 4753-59-7 ]
[ 871-66-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; zinc In N,N-dimethyl acetamide at 80℃; for 12h;	17 Example 1 General procedure: In the glove box, bis-(1,5-cyclooctadiene)nickel (8.3mg, 0.03mmol) and 2,2'-bipyridine, which is the chemical structural formula structural formula L1, (7.0mg, 0.045mmol) into the microwave tube,Add 0.225mL N,N-dimethylacetamide for coordination for one hour, add zinc powder (39.2mg, 0.6mmol, 2.0 equivalent) into the microwave tube,Then add succinic anhydride (0.45mmol, 1.5eq) and 1-bromooctane (0.3mmol, 1.0eq), cover it and take it out from the glove box, reflux at 80 for 12 hours,Cool to room temperature, uncap and add three drops of water to quench the reaction, remove the solvent under reduced pressure,The crude product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 11 alkanic acid (47.0 mg, 84% yield).

Reference： [1]Current Patent Assignee: NANJING TECH UNIVERSITY - CN111533649, 2020, A Location in patent: Paragraph 0028-0032; 0051

81
[ 185815-59-2 ]
[ 4753-59-7 ]
C₁₄H₂₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; zinc In N,N-dimethyl acetamide at 80℃; for 12h;	29 Example 1 General procedure: In the glove box, bis-(1,5-cyclooctadiene)nickel (8.3mg, 0.03mmol) and 2,2'-bipyridine, which is the chemical structural formula structural formula L1, (7.0mg, 0.045mmol) into the microwave tube,Add 0.225mL N,N-dimethylacetamide for coordination for one hour, add zinc powder (39.2mg, 0.6mmol, 2.0 equivalent) into the microwave tube,Then add succinic anhydride (0.45mmol, 1.5eq) and 1-bromooctane (0.3mmol, 1.0eq), cover it and take it out from the glove box, reflux at 80 for 12 hours,Cool to room temperature, uncap and add three drops of water to quench the reaction, remove the solvent under reduced pressure,The crude product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 11 alkanic acid (47.0 mg, 84% yield).

Reference： [1]Current Patent Assignee: NANJING TECH UNIVERSITY - CN111533649, 2020, A Location in patent: Paragraph 0028-0032; 0063

82
[ 108-30-5 ]
[ 4753-59-7 ]
[ 86013-76-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; zinc In N,N-dimethyl acetamide at 80℃; for 12h;	3 Example 1 General procedure: In the glove box, bis-(1,5-cyclooctadiene)nickel (8.3mg, 0.03mmol) and 2,2'-bipyridine, which is the chemical structural formula structural formula L1, (7.0mg, 0.045mmol) into the microwave tube,Add 0.225mL N,N-dimethylacetamide for coordination for one hour, add zinc powder (39.2mg, 0.6mmol, 2.0 equivalent) into the microwave tube,Then add succinic anhydride (0.45mmol, 1.5eq) and 1-bromooctane (0.3mmol, 1.0eq), cover it and take it out from the glove box, reflux at 80 for 12 hours,Cool to room temperature, uncap and add three drops of water to quench the reaction, remove the solvent under reduced pressure,The crude product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 11 alkanic acid (47.0 mg, 84% yield).

Reference： [1]Current Patent Assignee: NANJING TECH UNIVERSITY - CN111533649, 2020, A Location in patent: Paragraph 0028-0033; 0037

83
[ 4753-59-7 ]
[ 91568-44-4 ]
4-{4-[(4-methoxyphenyl)diazenyl]-3,5-dimethyl-1H-pyrazol-1-yl}butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate In acetonitrile Reflux;	Synthesis of pyrazoles 3f-k (general procedure) General procedure: A mixture of pyrazole 2b, c (1.5 mmol), haloalkane (3 mmol), and K2CO3 (0.31 g, 2.25 mmol) in MeCN (or acetone in the synthesis of compound 3k) (10 mL) was refluxed for 6-12 h. The precipitate was filtered off, and the mother liquor was concentrated. The products were purified by column chromatography using a hexane-ethyl acetate mixture (4 : 1) as the eluent.

Reference： [1]Burgart, Ya. V.; Evstigneeva, N. P.; Gerasimova, N. A.; Ivanova, A. E.; Khudina, O. G.; Saloutin, V. I. [Russian Chemical Bulletin, 2021, vol. 70, # 6, p. 1124 - 1130][Izv. Akad. Nauk, Ser. Khim., 2021, # 6, p. 1124 - 1130]

84
[ 41785-13-1 ]
[ 4753-59-7 ]
C₁₄H₂₁N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 8-propyl-7⁽⁹⁾<i>H</i>-purin-6-ylamine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 70℃; for 2h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 48h; Inert atmosphere;	61.1 (1) Synthesis of Compound VII General procedure: Take by weighing 30mmol compound I, join in the clean 250mL there-necked flask;After adding 150 mL of N,N-dimethylformamide, nitrogen was replaced three times; nitrogen protection;The ice-water bath was cooled to 0°C, and 65mmol sodium hydrogen (60% in oil) was weighed and added to the reaction system in batches; after adding, it was warming up to 70°C and stirred for 2 hours; then cooled to 0°C with an ice-water bath;Weigh 35mmol of 4-bromobutyl acetate and add it dropwise to the above reaction system; after adding, the room temperature does not remove the cooling bath, naturally heat up to room temperature, and stir at room temperature for 48 hours; filter, spin dry the filtrate in a high-vacuum water bath at 40°C After column chromatography (dichloromethane:methanol=9:1), a white solid was obtained;
	Stage #1: 8-propyl-7⁽⁹⁾<i>H</i>-purin-6-ylamine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 70℃; for 2h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 48h; Inert atmosphere;	61.1 (1) Synthesis of Compound VII General procedure: Take by weighing 30mmol compound I, join in the clean 250mL there-necked flask;After adding 150 mL of N,N-dimethylformamide, nitrogen was replaced three times; nitrogen protection;The ice-water bath was cooled to 0°C, and 65mmol sodium hydrogen (60% in oil) was weighed and added to the reaction system in batches; after adding, it was warming up to 70°C and stirred for 2 hours; then cooled to 0°C with an ice-water bath;Weigh 35mmol of 4-bromobutyl acetate and add it dropwise to the above reaction system; after adding, the room temperature does not remove the cooling bath, naturally heat up to room temperature, and stir at room temperature for 48 hours; filter, spin dry the filtrate in a high-vacuum water bath at 40°C After column chromatography (dichloromethane:methanol=9:1), a white solid was obtained;

Reference： [1]Current Patent Assignee: ZHONGYUAN HUIJI BIOTECHNOLOGY - CN113943324, 2022, A Location in patent: Paragraph 0075-0077
[2]Current Patent Assignee: ZHONGYUAN HUIJI BIOTECHNOLOGY - CN113943324, 2022, A Location in patent: Paragraph 0075-0077; 0084

85
[ 4753-59-7 ]
[ 1566-32-1 ]
C₁₁H₁₇N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.6%	Stage #1: 3-Methylmercapto-6-methyl-2H-1,2,4-triazinon-⁽⁵⁾ With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In tetrahydrofuran at 80℃; Inert atmosphere;	25 T114. A solution of T108 (0.15 g, 0.95 mmol) in dry THF (7 mL) was treated with LiHMDS (1M, 1.1 mL) at rt and the mixture was further stirred for 30 minute at the same temperature. 4- Bromobutyl acetate (0.74 g, 3.82 mmol) was added dropwise at rt then the mixture was stirred overnight at 80 °C under argon atmosphere. The mixture was cooled to rt and then aq. NH4CI (1 mL) was added. The whole was partitioned between EtOAc water. The organic phase work washed with water, brine, and separated. The combined organic phases were dried over anhydrous (Na2SO4), and filtered off. The filtrate was evaporated under vacuum and the residue was purified by silica gel column chromatography (eluate: 12% EtoAc / hexanes) to give compound T114 (112 mg, 44.6 % yield) as a white solid: UV-vis (MeOH) 235 nm; 1H- NMR (CDCI3) δ 4.11 (2H, t, 4’-CH2, J = 6.4 Hz), 4.01 (2H, t, 1’-CH2, J = 7.2 Hz), 2.58 (3H, s, S-CH3), 2.28 (3H, s, 5-CH3), 2.06 (3H, s, Ac), 1.91 (2H, m, H-2’), 1.70 (2H, m, 3’-CH2); 13C- NMR (CDCl3) δ 171.15, 164.89, 161.03, 150.78, 63.66, 54.63, 26.01, 25.01, 21.09, 17.14; 14.27.
44.6%	Stage #1: 3-Methylmercapto-6-methyl-2H-1,2,4-triazinon-⁽⁵⁾ With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In tetrahydrofuran at 80℃; Inert atmosphere;	25 T114. A solution of T108 (0.15 g, 0.95 mmol) in dry THF (7 mL) was treated with LiHMDS (1M, 1.1 mL) at rt and the mixture was further stirred for 30 minute at the same temperature. 4- Bromobutyl acetate (0.74 g, 3.82 mmol) was added dropwise at rt then the mixture was stirred overnight at 80 °C under argon atmosphere. The mixture was cooled to rt and then aq. NH4CI (1 mL) was added. The whole was partitioned between EtOAc water. The organic phase work washed with water, brine, and separated. The combined organic phases were dried over anhydrous (Na2SO4), and filtered off. The filtrate was evaporated under vacuum and the residue was purified by silica gel column chromatography (eluate: 12% EtoAc / hexanes) to give compound T114 (112 mg, 44.6 % yield) as a white solid: UV-vis (MeOH) 235 nm; 1H- NMR (CDCI3) δ 4.11 (2H, t, 4’-CH2, J = 6.4 Hz), 4.01 (2H, t, 1’-CH2, J = 7.2 Hz), 2.58 (3H, s, S-CH3), 2.28 (3H, s, 5-CH3), 2.06 (3H, s, Ac), 1.91 (2H, m, H-2’), 1.70 (2H, m, 3’-CH2); 13C- NMR (CDCl3) δ 171.15, 164.89, 161.03, 150.78, 63.66, 54.63, 26.01, 25.01, 21.09, 17.14; 14.27.
44.6%	Stage #1: 3-Methylmercapto-6-methyl-2H-1,2,4-triazinon-⁽⁵⁾ With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-Bromobutyl acetate In tetrahydrofuran at 80℃; Inert atmosphere;	25 T114. A solution of T108 (0.15 g, 0.95 mmol) in dry THF (7 mL) was treated with LiHMDS (1M, 1.1 mL) at rt and the mixture was further stirred for 30 minute at the same temperature. 4- Bromobutyl acetate (0.74 g, 3.82 mmol) was added dropwise at rt then the mixture was stirred overnight at 80 °C under argon atmosphere. The mixture was cooled to rt and then aq. NH4CI (1 mL) was added. The whole was partitioned between EtOAc water. The organic phase work washed with water, brine, and separated. The combined organic phases were dried over anhydrous (Na2SO4), and filtered off. The filtrate was evaporated under vacuum and the residue was purified by silica gel column chromatography (eluate: 12% EtoAc / hexanes) to give compound T114 (112 mg, 44.6 % yield) as a white solid: UV-vis (MeOH) 235 nm; 1H- NMR (CDCI3) δ 4.11 (2H, t, 4’-CH2, J = 6.4 Hz), 4.01 (2H, t, 1’-CH2, J = 7.2 Hz), 2.58 (3H, s, S-CH3), 2.28 (3H, s, 5-CH3), 2.06 (3H, s, Ac), 1.91 (2H, m, H-2’), 1.70 (2H, m, 3’-CH2); 13C- NMR (CDCl3) δ 171.15, 164.89, 161.03, 150.78, 63.66, 54.63, 26.01, 25.01, 21.09, 17.14; 14.27.

Reference： [1]Current Patent Assignee: SINCE TECH DEVELOPMENT FUND AUTHORITY - WO2022/8025, 2022, A1 Location in patent: Page/Page column 67; 94-95
[2]Current Patent Assignee: SINCE TECH DEVELOPMENT FUND AUTHORITY - WO2022/8025, 2022, A1 Location in patent: Page/Page column 67; 94-95
[3]Current Patent Assignee: SINCE TECH DEVELOPMENT FUND AUTHORITY - WO2022/8025, 2022, A1 Location in patent: Page/Page column 67; 94-95

86
[ 4753-59-7 ]
1,2,3,4-tetrahydro-2,4-dioxo-6-[4-(propan-2-yl)-phenyl]pyrimidine-5-carbonitrile [ No CAS ]
4-{5-cyano-2,4-dioxo-6-[4-(propan-2-yl)phenyl]-3,4-dihydropyrimidin-1(2H)-yl}butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate In propan-2-one at 20℃; for 1h;	General Procedure for the synthesis of acyclicnucleosides 2a-2h and 3a-3h. General procedure: A mixture of pyrimidine-5-carbonitrile 1a or 1b (0.01 mol) and potassiumcarbonate (0.011 mol) in anhydrous acetone (30 mL)was stirred at room temperature for 1 h. 4-Bromobutylacetate [18], 2-(bromomethoxy)ethyl acetate [18],3-chloropropan-1-ol, epichlorohydrin, allyl bromide, orpropargyl bromide (0.011 mol) was then added, and themixture was stirred for 8-12 h at room temperature andfiltered, and the filtrate was evaporated. The residuewas recrystallized from an appropriate solvent. 4-{5-Cyano-2,4-dioxo-6-[4-(propan-2-yl)phenyl]-3,4-dihydropyrimidin-1(2H)-yl}butyl acetate (2a).Yield 80%, colorless solid (from EtOH), mp 136-138°C. IR spectrum, ., cm-1: 3441 (NH), 2232 (CN),1723, 1665 (C=O). 1H NMR spectrum, d, ppm: 1.25 d(6H, 3J= 6.30 Hz,Me2CH),1.54 m (2H, 3'-H), 1.65 m(2H, 2'-H), 1.98 s (3H, MeCO), 2.99 m (1H ,Me2CH),3.46 t (2H, 3J = 5.12 Hz, 1'-H), 3.88 t (2H, 3J =5.80 Hz, 4'-H), 7.36 d (2H, 3J = 8.10 Hz,Harom),7.78 d(2H, 3J= 8.10 Hz,Harom),10.84 s (1H, NH). 13C NMRspectrum,dC,ppm: 24.2, 39.81, 20.92, 25.22, 25.64,62.31, 68.67, 115.8, 127.1, 128.3, 148.1, 153.6, 158.6,160.2, 162.7, 168.9 and 170.2. Found, %: C 64.91;H 6.32; N 11.43.C20H23N3O4.Calculated, %: C 65.03;H 6.28; N 11.37.

Reference： [1]Alkabli, J.; Moustafa, A. H. [Russian Journal of Organic Chemistry, 2022, vol. 58, # 3, p. 385 - 393][Zh. Org. Khim.]

87
[ 339235-45-9 ]
[ 4753-59-7 ]
4-({5-cyano-6-oxo-4-[4-(propan-2-yl)phenyl]-1,6-dihydropyrimidin-2-yl}sulfanyl)butyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate In propan-2-one at 20℃; for 1h;	General Procedure for the synthesis of acyclicnucleosides 2a-2h and 3a-3h. General procedure: A mixture of pyrimidine-5-carbonitrile 1a or 1b (0.01 mol) and potassiumcarbonate (0.011 mol) in anhydrous acetone (30 mL)was stirred at room temperature for 1 h. 4-Bromobutylacetate [18], 2-(bromomethoxy)ethyl acetate [18],3-chloropropan-1-ol, epichlorohydrin, allyl bromide, orpropargyl bromide (0.011 mol) was then added, and themixture was stirred for 8-12 h at room temperature andfiltered, and the filtrate was evaporated. The residuewas recrystallized from an appropriate solvent. 4-{5-Cyano-2,4-dioxo-6-[4-(propan-2-yl)phenyl]-3,4-dihydropyrimidin-1(2H)-yl}butyl acetate (2a).Yield 80%, colorless solid (from EtOH), mp 136-138°C. IR spectrum, ., cm-1: 3441 (NH), 2232 (CN),1723, 1665 (C=O). 1H NMR spectrum, d, ppm: 1.25 d(6H, 3J= 6.30 Hz,Me2CH),1.54 m (2H, 3'-H), 1.65 m(2H, 2'-H), 1.98 s (3H, MeCO), 2.99 m (1H ,Me2CH),3.46 t (2H, 3J = 5.12 Hz, 1'-H), 3.88 t (2H, 3J =5.80 Hz, 4'-H), 7.36 d (2H, 3J = 8.10 Hz,Harom),7.78 d(2H, 3J= 8.10 Hz,Harom),10.84 s (1H, NH). 13C NMRspectrum,dC,ppm: 24.2, 39.81, 20.92, 25.22, 25.64,62.31, 68.67, 115.8, 127.1, 128.3, 148.1, 153.6, 158.6,160.2, 162.7, 168.9 and 170.2. Found, %: C 64.91;H 6.32; N 11.43.C20H23N3O4.Calculated, %: C 65.03;H 6.28; N 11.37.

Reference： [1]Alkabli, J.; Moustafa, A. H. [Russian Journal of Organic Chemistry, 2022, vol. 58, # 3, p. 385 - 393][Zh. Org. Khim.]

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CAS No. :	4753-59-7	MDL No. :	MFCD00000263
Formula :	C₆H₁₁BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UOABIRUEGSGTSA-UHFFFAOYSA-N
M.W :	195.05	Pubchem ID :	78491
Synonyms :

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.83
Num. rotatable bonds :	5
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	40.11
TPSA :	26.3 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.07 cm/s

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

[ CAS No. 4753-59-7 ] {[proInfo.proName]}

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[ 4753-59-7 ]

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Log Po/w (iLOGP) :	2.31
Log Po/w (XLOGP3) :	2.0
Log Po/w (WLOGP) :	1.72
Log Po/w (MLOGP) :	1.79
Log Po/w (SILICOS-IT) :	1.73
Consensus Log Po/w :	1.91

Log S (ESOL) :	-1.98
Solubility :	2.05 mg/ml ; 0.0105 mol/l
Class :	Very soluble
Log S (Ali) :	-2.18
Solubility :	1.29 mg/ml ; 0.00662 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.43
Solubility :	0.723 mg/ml ; 0.00371 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.83

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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[ CAS No. 4753-59-7 ] {[proInfo.proName]}

Quality Control of [ 4753-59-7 ]

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[ 4753-59-7 ]