Name: 2040-04-2|2',6'-Dimethoxyacetophenone|98%
Brand: Ambeed
SKU: A434225
Price: 11.0 USD
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1
[ 917-64-6 ]
[ 16932-49-3 ]
[ 2040-04-2 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1934,vol. <2>139,p. 290,292

2
[ 2040-04-2 ]
1-(2,6-dimethoxy-phenyl)-ethanone oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydroxylamine hydrochloride; sodium acetate In methanol; water Reflux;	19. All of the oxime substrates used in this investigation were synthesized in quantitative yields by refluxing a mixture of 1 equiv of the corresponding ketones or aldehydes, 1.6 equiv of hydroxylamine hydrochloride, and 2.0 equiv of sodium acetate in aqueous methanol.

Reference： [1]Location in patent: experimental part Augustine, John Kallikat; Kumar, Rajesha; Bombrun, Agnes; Mandal, Ashis Baran [Tetrahedron Letters, 2011, vol. 52, # 10, p. 1074 - 1077]
[2]Schamschurin [Zhurnal Obshchei Khimii, 1945, vol. 15, p. 978,979][Chem.Abstr., 1946, p. 6451]

3
[ 2040-04-2 ]
[ 18610-90-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	With hydrogen In methanol
90%	With hydrogen; toluene-4-sulfonic acid In methanol at 25℃; for 24h;
55.2%	With [{κ3-N,Si,C-PhB(4,4-dimethyl-2-oxazoline)((4,4-dimethyl-2-oxazoline)SiHPh)(1-mesitylimidazole)}Rh(H)CO][HB(C6F5)3]; phenylsilane In dichloromethane at 25℃; for 24h; Inert atmosphere; Schlenk technique; Glovebox;

Reference： [1]Roth; Aig; Rauckman; Strelitz; Phillips; Ferone; Bushby; Sigel [Journal of Medicinal Chemistry, 1981, vol. 24, # 8, p. 933 - 941]
[2]Krow, Grant R.; Miles, William H.; Smiley, Patricia M.; Lester, Walden S.; Kim, Yong J. [Journal of Organic Chemistry, 1992, vol. 57, # 14, p. 4040 - 4043]
[3]Xu, Songchen; Boschen, Jeffery S.; Biswas, Abhranil; Kobayashi, Takeshi; Pruski, Marek; Windus, Theresa L.; Sadow, Aaron D. [Dalton Transactions, 2015, vol. 44, # 36, p. 15897 - 15904]

4
[ 2040-04-2 ]
[ 100-52-7 ]
[ 145629-34-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In ethanol for 24h; Ambient temperature;
49.9%	With sodium hydroxide In methanol; water at 20℃; for 1h;
49%	With potassium hydroxide In methanol at 70℃;

Reference： [1]Batt; Goodman; Jones; Kerr; Mantegna; McAllister; Newton; Nurnberg; Welch; Covington [Journal of Medicinal Chemistry, 1993, vol. 36, # 10, p. 1434 - 1442]
[2]Robinson, Thomas Philip; Hubbard IV, Richard B.; Ehlers, Tedman J.; Arbiser, Jack L.; Goldsmith, David J.; Bowen, J. Phillip [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 12, p. 4007 - 4013]
[3]Boumendjel, Ahcène; Boccard, Julien; Carrupt, Pierre-Alain; Nicolle, Edwige; Blanc, Madeleine; Geze, Annabelle; Choisnard, Luc; Wouessidjewe, Denis; Matera, Eva-Laure; Dumontet, Charles [Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2307 - 2310]

5
[ 2040-04-2 ]
[ 99501-03-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With RuBr₂[(S,S)-2,4-bis-(di-3,5-xylylphosphino)pentane]-2-picolylamine; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 40℃; for 21h; Autoclave; Inert atmosphere;	19 In an autoclave, 3.12 mg (3.38 × 10 -3 mmol, S / C = 1000) of RuBr 2 [(S, S) - xylskewphos] (pica)And 7.64 mg (6.81 × 10 -2 mmol) of potassium tert-butoxide were charged and purged with argon gas. Under argon gas flow, 0.5 mL (3.39 mmol) of 2 ', 6'-dichloro-3'-fluoroacetophenone and 2.9 mL of 2-propanol were weighed with a syringe and pressurized to 10 atm with hydrogen, After stirring at 40 ° C. for 21 hours, reduction in hydrogen pressure was confirmed, and (S) -1- (2,6-dichloro-3-fluorophenyl) ethanol was obtained in 100% yield. In addition, HPLC (DAICEL CHRALPAK AD-RH, acetonitrile / water = 25/75, 0.5 mL / min, 25 ° C., 220 nm, retention time of each enantiomer is 56.1 min in the (S) 64.5 min), the optical purity was found to be 94.0% ee. The same conditions as in Example 1 were carried out except that S / C, substrate concentration, potassium tert-butoxide (KOtBu) concentration was changed for the purpose of improving the efficiency of the reaction. As a result, it was confirmed that the substrate was hydrogenated almost quantitatively under the condition of S / C = 20000. In addition, all the alcohol bodies formed were the (S) isomer as the main component. hydrogenation reaction ofketones with ortho di-substituted phenyl group other than 2 ',6'-dichloro-3'-fluoroacetophenone was carried out. An ortho-disubstituted phenyl group other than 2 ', 6'-dichloro-3'-fluoroacetophenoneTo carry out the hydrogenation reaction of the ketone.The reaction was carried out in the same manner as in Example 15, except that S / C = 2000.However, in Examples 19 and 22,In consideration of the solubility of the substrate, the substrate concentration was 1.0 mol / L.
95%	Stage #1: 2,6-dimethoxyacetophenone With zinc diacetate In tetrahydrofuran at 65℃; for 0.166667h; Stage #2: With methyl-di(n-propoxy)silane In tetrahydrofuran at 65℃; for 12h; Stage #3: With potassium fluoride; tetrabutyl ammonium fluoride In tetrahydrofuran at 0℃; for 2h;
91%	With C₃₆H₁₀₃AlO₄Si₁₄; isopropyl alcohol In neat (no solvent) at 80℃; for 24h; Glovebox; Schlenk technique;

67%	With C₁₅H₁₈BF₃; hydrogen; tert-butylimino-tri(pyrrolidino)phosphorane In tetrahydrofuran at 75℃; for 40h;
60%	With zirconium dioxide hydrate; isopropyl alcohol at 130℃; for 0.75h;
	With sodium tetrahydroborate In methanol for 0.75h;
	With (-)-diisopinocamphenylborane chloride In diethyl ether at 20℃; for 48h;
	With lithium aluminium tetrahydride In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Schlenk technique; Glovebox;

Reference： [1]Current Patent Assignee: HOKKAIDO UNIVERSITY; KANTO KAGAKU HOLDINGS K.K. - JP2015/24975, 2015, A Location in patent: Paragraph 0132; 0140; 0141; 0144; 0151
[2]Location in patent: experimental part Inagaki, Tomohiko; Yamada, Yoko; Le, Thanh Phong; Furuta, Akihiro; Ito, Jun-Ichi; Nishiyama, Hisao [Synlett, 2009, # 2, p. 253 - 256]
[3]McNerney, Brian; Whittlesey, Bruce; Cordes, David B.; Krempner, Clemens [Chemistry - A European Journal, 2014, vol. 20, # 46, p. 14959 - 14964]
[4]Mummadi, Suresh; Brar, Amandeep; Wang, Guoqiang; Kenefake, Dustin; Diaz, Rony; Unruh, Daniel K.; Li, Shuhua; Krempner, Clemens [Chemistry - A European Journal, 2018, vol. 24, # 62, p. 16526 - 16531]
[5]Battilocchio, Claudio; Hawkins, Joel M.; Ley, Steven V. [Organic Letters, 2013, vol. 15, # 9, p. 2278 - 2281]
[6]Knauer, Birgit; Krohn, Karsten [Liebigs Annalen, 1995, # 4, p. 677 - 684]
[7]Ramachandran, P. Veeraraghavan; Gong, Baoqing; Brown, Herbert C.; Francisco, Joseph S. [Tetrahedron Letters, 2004, vol. 45, # 12, p. 2603 - 2605]
[8]Lau, Samantha; Ward, Bryan; Zhou, Xueer; White, Andrew J.P.; Casely, Ian J.; MacGregor, Stuart A.; Crimmin, Mark R. [Organometallics, 2017, vol. 36, # 18, p. 3654 - 3663]

6
[ 2040-04-2 ]
1-(2,6-dimethoxy-phenyl)-2-iodo-ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With iodine; Selectfluor In methanol at 20℃; for 29h;
73%	Stage #1: 2,6-dimethoxyacetophenone With sulfuric acid; sodium dodecyl-sulfate In water at 60℃; Stage #2: With iodine In water at 60℃; Stage #3: With sodium nitrite In water at 60℃; regioselective reaction;
54%	With sulfuric acid; dihydrogen peroxide; iodine at 50℃; for 18h;

Reference： [1]Stavber, Stojan; Jereb, Marjan; Zupan, Marko [Chemical Communications, 2002, # 5, p. 488 - 489]
[2]Location in patent: experimental part Stavber, Gaj; Iskra, Jernej; Zupan, Marko; Stavber, Stojan [Green Chemistry, 2009, vol. 11, # 8, p. 1262 - 1267]
[3]Pavlinac, Jasminka; Zupan, Marko; Stavber, Stojan [Synthesis, 2006, # 15, p. 2603 - 2607]

7
[ 2040-04-2 ]
[ 123184-19-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With phenyltrimethylammonium tribromide In tetrahydrofuran at 20℃; for 1.16667h;	C.14 (C-14) To a solution of the above-mentioned compound C-13 (4.0g, 22.2mmol) in tetrahydrofuran (40ml), was added phenyltrimethylammoniumtribromide (8.34g, 22.2mmol) over 10 minutes at room temperature and the mixture was stirred at the same temperature for 1 hour.. water was added thereto, and the mixture was extracted with ethyl acetate, washed, and dried, then the solvent was evaporated under reduced pressure.. The residue was purified with silica gel column chromatography (ethyl acetate:n-hexane=1:4).. After allowing to stand at room temperature, the obtained solid residue was washed with diisopropylether to give 2-bromo-1-(2,6-dimethoxyphenyl)etanone (4.22g yield: 70%). Melting point: 78-82°C NMR(CDCl3)δ: 3.82(6H, s), 4.38(2H, s), 6.57(2H, d, J=8.4Hz), 7.32(1H, t, J=8.4Hz).
57%	With copper(I) bromide In chloroform; ethyl acetate at 12℃; Reflux;
40%	With N-Bromosuccinimide; toluene-4-sulfonic acid In dichloromethane at 40℃; for 0.25h; Microwave irradiation; Green chemistry;

	With 4-dimethylaminopyridine tribromide; acetic acid
	With bromine In chloroform Heating;

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - EP1422218, 2004, A1 Location in patent: Page 188
[2]Hampannavar, Girish A.; Karpoormath, Rajshekhar; Palkar, Mahesh B.; Shaikh, Mahamadhanif S.; Chandrasekaran, Balakumar [ACS Medicinal Chemistry Letters, 2016, vol. 7, # 7, p. 686 - 691]
[3]Rodríguez, Juan C.; Maldonado, Rony A.; Ramírez-García, Gonzalo; Díaz Cervantes, Erik; de la Cruz, Fabiola N. [Journal of Heterocyclic Chemistry, 2020, vol. 57, # 5, p. 2279 - 2287]
[4]Jaramillo, Carlos; De Diego, J. Eugenio; Hamdouchi, Chafiq [Synlett, 2002, # 9, p. 1544 - 1546]
[5]Skoumbourdis, Amanda P.; Huang, Ruili; Southall, Noel; Leister, William; Guo, Vicky; Cho, Ming-Hsuang; Inglese, James; Nirenberg, Marshall; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 4, p. 1297 - 1303]

8
[ 2040-04-2 ]
[ 5123-13-7 ]
1-[1,1';3',1"]terphenyl-2'-yl-ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II) In toluene for 1h; Heating;
45 %Chromat.	With styrene; carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II); cesium fluoride In toluene at 120℃; for 0.5h;
94 %Chromat.	With carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II) In toluene at 125℃; for 20h; Schlenk technique;	V. General Procedure for C-O Diarylation of 2’,6’-Dimethoxyacetophenone (6) General procedure: To an oven-dried 20 mL Schlenk tube containing a magnetic stirring bar were added 2’,6’-dimethoxyacetophenone (6) (0.5mmol), arylboronate 2 (1.5 mmol), RuH2(CO)(PPh3)3 (0.05 mmol), and 0.5 mL of dry toluene. The resulting mixture washeated at 125 °C for 20 h and cooled to room temperature. Hexacosane was added as an internal standard to the mixture,which was then analyzed by GC. The crude material was passed through a basic aluminium oxide column to remove theremaining arylboronate. Further purification of the product was performed by silica gel column chromatography(hexane:AcOEt = 20:1). Diarylation Product 7a Following the general procedure, diarylation product 7a was obtained as a white solid. The analytical datafor 7a are in good agreement with those reported in literature.3

Reference： [1]Kakiuchi, Fumitoshi; Usui, Mayumi; Ueno, Satoshi; Chatani, Naoto; Murai, Shinji [Journal of the American Chemical Society, 2004, vol. 126, # 9, p. 2706 - 2707]
[2]Kondo, Hikaru; Kochi, Takuya; Kakiuchi, Fumitoshi [Organic Letters, 2017, vol. 19, # 4, p. 794 - 797]
[3]Izumoto, Akiko; Kondo, Hikaru; Kochi, Takuya; Kakiuchi, Fumitoshi [Synlett, 2017, vol. 28, # 19, p. 2609 - 2613]

9
[ 2040-04-2 ]
[ 83-38-5 ]
(E)-3-(2,6-Dichloro-phenyl)-1-(2,6-dimethoxy-phenyl)-propenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium hydroxide In methanol at 70℃;
	With potassium hydroxide In ethanol; water cooling;

Reference： [1]Boumendjel, Ahcène; Boccard, Julien; Carrupt, Pierre-Alain; Nicolle, Edwige; Blanc, Madeleine; Geze, Annabelle; Choisnard, Luc; Wouessidjewe, Denis; Matera, Eva-Laure; Dumontet, Charles [Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2307 - 2310]
[2]Robinson, Thomas Philip; Hubbard IV, Richard B.; Ehlers, Tedman J.; Arbiser, Jack L.; Goldsmith, David J.; Bowen, J. Phillip [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 12, p. 4007 - 4013]

10
[ 2040-04-2 ]
[ 3392-97-0 ]
(E)-1,3-Bis-(2,6-dimethoxy-phenyl)-propenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium hydroxide In methanol at 70℃;
	With potassium hydroxide In ethanol; water cooling;

Reference： [1]Boumendjel, Ahcène; Boccard, Julien; Carrupt, Pierre-Alain; Nicolle, Edwige; Blanc, Madeleine; Geze, Annabelle; Choisnard, Luc; Wouessidjewe, Denis; Matera, Eva-Laure; Dumontet, Charles [Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2307 - 2310]
[2]Robinson, Thomas Philip; Hubbard IV, Richard B.; Ehlers, Tedman J.; Arbiser, Jack L.; Goldsmith, David J.; Bowen, J. Phillip [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 12, p. 4007 - 4013]

11
[ 2040-04-2 ]
[ 65185-58-2 ]
[2-(2-Bromo-phenyl)-ethyl]-[1-(2,6-dimethoxy-phenyl)-eth-(E)-ylidene]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With 4 A molecular sieve In benzene at 25℃; for 10h;

Reference： [1]Viswanathan, Rajesh; Prabhakaran, Erode N.; Plotkin, Michael A.; Johnston, Jeffrey N. [Journal of the American Chemical Society, 2003, vol. 125, # 1, p. 163 - 168]

12
[ 2040-04-2 ]
[ 64-04-0 ]
[1-(2,6-Dimethoxy-phenyl)-eth-(E)-ylidene]-phenethyl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With 4 A molecular sieve In benzene at 25℃;

Reference： [1]Viswanathan, Rajesh; Prabhakaran, Erode N.; Plotkin, Michael A.; Johnston, Jeffrey N. [Journal of the American Chemical Society, 2003, vol. 125, # 1, p. 163 - 168]

13
[ 2040-04-2 ]
[ 103068-41-3 ]

Reference： [1]Canadian Journal of Chemistry,1988,vol. 66,p. 1479 - 1482

14
[ 2040-04-2 ]
[ 126829-31-0 ]

Reference： [1]Tetrahedron Letters,1990,vol. 31,p. 6753 - 6756

15
[ 2040-04-2 ]
[ 121083-00-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With ammonium hydroxide; ammonium acetate; sodium cyanoborohydride; zinc In ethanol; water at 80℃; for 36h;	4.2.1. General procedure for the synthesis of amines via reductive amination of acetophenones General procedure: To a saturated solution of NH4OAc in EtOH (40 mL) were added activated Zn (5 equiv), acetophenone (1 equiv), NaBCNH3(3 equiv) and 30% aq NH3 (10 mL) respectively. The mixture wasstirred at 80 C for 36 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and made basic using 1 M NaOH (50 mL). Theorganic phase was separated and aqua phase was extracted with (2x25 mL) CH2Cl2. The organic phases were combined and acidified with HCl (pH: 2.0). The organic layer was separated andH2O layer was extracted with CH2Cl2 (2 25 mL). The H2O layer was made basic with NaOH (pH: 10.0), The organic layer was extracted with CH2Cl2 (3 25 mL). Combined organic layers weredried over Na2SO4 and evaporation of the solvent afforded thedesired amines.
	Multi-step reaction with 2 steps 2: sodium-amalgam; acetic acid; water

Reference： [1]Akincioʇlu, Akin; Akincioʇlu, Hülya; Gülçin, Ilhami; Durdagi, Serdar; Supuran, Claudiu T.; Göksu, Süleyman [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3592 - 3602]
[2]Schamschurin [Zhurnal Obshchei Khimii, 1945, vol. 15, p. 978,979][Chem.Abstr., 1946, p. 6451]

16
[ 699-83-2 ]
[ 74-88-4 ]
[ 2040-04-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;	Example 6 (S)-N-(2-cymo- 1 -( 1 -hydroxy-7-isopropyl- 1 ,3 -dihydrobenzo [c] [ 1 ,2"\|oxaborol-6-yloxy")pro pan-2-yl')-4-('trifluoromethoxy')benzamide To a solution of l-(2,6-dihydroxyphenyl)ethanone (50.0g, 329.0mmol) and potassium carbonate (136.2g, 986.8mmol) in DMF (200mL) is added CH3I (48.6mL, 822.5mmol) slowly at rt. The mixture is stirred for 16h at rt, poured into ice water (lOOOmL) and stirred for 30 min. The precipitate is filtered, washed with water and dried to give the desired product as a light yellow solid (50g, yield 84%).
84%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;	To a solution of compound l-(2,6-dihydroxyphenyl)ethanone (25.0 g, 164.5 mmol) and potassium carbonate (68.1 g, 493.4 mmol) in DMF (100 mL) was added iodomethane (24.3 mL, 41 1.2 mmol) slowly at room temperature. The mixture was stirred for 16 h at room temperature. The mixture was poured into ice water (500 mL) and stirred for 30 min. The precipitate was filtered, washed with water and dried to give l-(2,6-dimethoxyphenyl)ethanone as a light yellow solid (25 g, yield 84%). MS: m/z =181.0 (M+H, ESI+).
71%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	(C-13) To a suspension of 2', 6'-dihydroxyacetophenone (5.0g, 32.9mmol) and powder potassium carbonate (10.0g, 72.4mmol) in dimethylformamide (30ml), was added iodomethane (7.1ml, 114mmol) at room temperature and the mixture was stirred at the same temperature overnight.. To the solution was added 2N hydrochloric acid (45ml) and water (45ml) and the precipitated crystals were filtered off.. The crude crystals were washed with water and dried, then crystallized from ethyl acetate / n-hexane to give 1-(2,6-dimethoxyphenyl)etanone (4.2g, yield: 71%). Melting point: 69C NMR(CDCl3)delta:2.48(3H, s), 3.81(6H, s), 6.55(2H, d, J=8.1Hz), 7.26(1H, t, J=8.1Hz).

Reference： [1]Patent: WO2014/149793,2014,A1 .Location in patent: Page/Page column 51
[2]Patent: WO2015/13318,2015,A1 .Location in patent: Paragraph 0244
[3]Patent: EP1422218,2004,A1 .Location in patent: Page 188

17
[ 4460-86-0 ]
[ 2040-04-2 ]
[ 944447-13-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium hydroxide In methanol at 70℃;
62%	With lithium hydroxide monohydrate In ethanol at 40℃; for 5.5h;	B.B.1 Preparation of Chalcones Via Claisen-Schmidt Condensation. General procedure: A solution of the acetophenone (10 mmol) and LiOH.H2O (10 mol %) in 10 mL of absolute ethanol is stirred at the appropriate temperature for 10 min (for reactions at 40° C., the bulb is equipped with a reflux condenser). Then, the benzaldehyde (10 mmol, 1 equiv.) is added and the system is protected from the atmosphere with a cork stopper. Reaction progress is monitored by TLC or LCMS-analysis; during the course of the reaction, the chalcone may precipitate. Upon attaining maximum conversion grade, the reaction mixture is quenched with 15 mL of 1% hydrochloric acid. [0362] If the chalcone has precipitated, it is isolated by means of filtration. In order to remove residual amounts of benzaldehyde, the residue is washed thoroughly with water until the filtrate turns clear. The obtained solid is the chalcone, which can be dried in a dessicator. Subsequently, the chalcone can be recrystallized in absolute ethanol so as to obtain high purity crystals. [0363] If the chalcone has formed a separate oily liquor at the bottom of the bulb, it can be extracted from the mixture with diethyl ether. The organic phase is subsequently washed with brine (2×) and dried over MgSO4, upon which the solution is concentrated in vacuo. Again, purification of the thus obtained residue can be performed through recrystallization in absolute ethanol. [0369] The synthesis of compounds 37-51 was conducted via a Claisen-Schmidt condensation of suitably functionalized acetophenones and benzaldehydes. Whilst other syntheses have been proposed to prepare chalcones (e.g. via 1,3-diaryl-1-siloxy allenes or by Suzuki or Heck coupling reactions), this crossed aldol condensation remains the method of choice, given its simplicity and the ready availability of the required acetophenones 35 and benzaldehydes 36. Wherein R and R′ are as represented in table 3 Scheme: [0370] Chalcone synthesis. a) 1 equiv. benzaldehyde 36, 5 mol % LiOH.H2O, abs. EtOH., conditions see table 3. [0371] Over the years, numerous basic (e.g. NaOH, Ba(OH)2 and Al2O3) and acid (e.g. dry HCl and BF3) catalysts have been proposed for this transformation. We considered the LiOH.H2O catalyzed protocol as proposed by Bhagat and co-workers to be the most elegant, because of its high catalyst turnover and yields, short reaction times and easy work-up. Nevertheless, as we could only obtain the high yields reported by these researchers after prolonged reaction times, we evaluated the influence of the reaction temperature on its outcome. As such, by rising the temperature to 40 or 70° C., and by optimizing the work-up procedure, we were able to obtain the pure chalcones 37-51 in reasonable to excellent yield after crystallization in ethanol (see table 3). [TABLE-US-00003] TABLE 3 Synthesis conditions and yield for the synthetic chalcones 37-51 in the training set. Reaction conditions Temperaturea Time Yieldb R R′ (° C.) (h) (%) 37 H H 20 .83 74 38 4′-MeO H 20 2 80 39 H 4-MeO 20 3 77 40 4′-MeO 4-MeO 40 2 82 41 4′-MeO 3-MeO 20 1 62 42 2′,4′,6′-triMeO 2,4,5-triMeO 20 168 78 43 2′,4′,6′-triMeO 4-MeO 20 86 69 44 4′-MeO 2,4,5-triMeO 20 15 92 45 4′-MeO 2,4,6-triMeO 70 2 89 46 2′,6′-diMeO 2,4,5-triMeO 40 5.5 62 47 2′,6′-diMeO 2,4,6-triMeO 40 48 64 48 4′-MeO 4-F 20 4 91 49 3′,4′,5′-triMeO 4-F 20 24 69 50 4′-F 4-F 20 1 42 51 H 4-F 40 2 51 [0372] The synthesis of compounds 52-55 was conducted in a similar way as described above for compounds 37-51, and the synthesis conditions are as depicted in table 4. [TABLE-US-00004] TABLE 4 Synthesis conditions and yield for the synthetic chalcones 52-55. R R′ Conditions Yielda (%) 52 4′-MeO 4-Cl r.t., 2 h 85 53 4′-F 3-F r.t., 1 h 15 min 70 54 4′-MeO 3-F r.t., 30 min 76 55 4′-MeO 2-F r.t., 4 h 88
62%	With lithium hydroxide monohydrate In ethanol at 40℃; for 5.5h;	Preparation of chalcones via Claisen-Schmidt condensation General procedure: A solution of the acetophenone(10 mmol) and LiOH.H2O (10 mol%) in 10 mL of absoluteethanol is stirred at the appropriate temperature for 10 min (for reactions at40 °C, the bulb is equipped with a reflux condenser). Then, the benzaldehyde(10 mmol, 1 equiv.) is added and the system is protected from theatmosphere with a cork stopper. Reaction progress is monitored by TLC orLCMS-analysis; during the course of the reaction, the chalcone may precipitate.Upon attaining maximum conversion grade, the reaction mixture is quenched with15 mL of 1% hydrochloric acid.If the chalcone has precipitated, it isisolated by means of filtration. In order to remove residual amounts ofbenzaldehyde, the residue is washed thoroughly with water until the filtrateturns clear. The obtained solid is the chalcone, which can be dried in adessicator. Subsequently, the chalcone can be recrystallized in absoluteethanol so as to obtain high purity crystals.If the chalcone has formed a separate oilyliquor at the bottom of the bulb, it can be extracted from the mixture withdiethyl ether. The organic phase is subsequently washed with brine (2x) anddried over MgSO4, upon which the solution is concentrated in vacuo. Again, purification of the thusobtained residue can be performed through recrystallization in absoluteethanol.Detailed reaction conditions and yields for chalcones 35-50are provided in Table S13

Reference： [1]Boumendjel, Ahcène; Boccard, Julien; Carrupt, Pierre-Alain; Nicolle, Edwige; Blanc, Madeleine; Geze, Annabelle; Choisnard, Luc; Wouessidjewe, Denis; Matera, Eva-Laure; Dumontet, Charles [Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2307 - 2310]
[2]Current Patent Assignee: GHENT UNIVERSITY - US2015/11620, 2015, A1 Location in patent: Paragraph 0361-0363; 0369-0372
[3]Roman, Bart I.; De Ryck, Tine; Patronov, Atanas; Slavov, Svetoslav H.; Vanhoecke, Barbara W.A.; Katritzky, Alan R.; Bracke, Marc E.; Stevens, Christian V. [European Journal of Medicinal Chemistry, 2015, vol. 101, p. 627 - 639]

18
[ 830-79-5 ]
[ 2040-04-2 ]
[ 944447-03-4 ]

Yield	Reaction Conditions	Operation in experiment
64%	With lithium hydroxide monohydrate; In ethanol; at 40℃; for 48h;	General procedure: A solution of the acetophenone (10 mmol) and LiOH.H2O (10 mol %) in 10 mL of absolute ethanol is stirred at the appropriate temperature for 10 min (for reactions at 40 C., the bulb is equipped with a reflux condenser). Then, the benzaldehyde (10 mmol, 1 equiv.) is added and the system is protected from the atmosphere with a cork stopper. Reaction progress is monitored by TLC or LCMS-analysis; during the course of the reaction, the chalcone may precipitate. Upon attaining maximum conversion grade, the reaction mixture is quenched with 15 mL of 1% hydrochloric acid. [0362] If the chalcone has precipitated, it is isolated by means of filtration. In order to remove residual amounts of benzaldehyde, the residue is washed thoroughly with water until the filtrate turns clear. The obtained solid is the chalcone, which can be dried in a dessicator. Subsequently, the chalcone can be recrystallized in absolute ethanol so as to obtain high purity crystals. [0363] If the chalcone has formed a separate oily liquor at the bottom of the bulb, it can be extracted from the mixture with diethyl ether. The organic phase is subsequently washed with brine (2×) and dried over MgSO4, upon which the solution is concentrated in vacuo. Again, purification of the thus obtained residue can be performed through recrystallization in absolute ethanol. [0369] The synthesis of compounds 37-51 was conducted via a Claisen-Schmidt condensation of suitably functionalized acetophenones and benzaldehydes. Whilst other syntheses have been proposed to prepare chalcones (e.g. via 1,3-diaryl-1-siloxy allenes or by Suzuki or Heck coupling reactions), this crossed aldol condensation remains the method of choice, given its simplicity and the ready availability of the required acetophenones 35 and benzaldehydes 36. Wherein R and R? are as represented in table 3 Scheme: [0370] Chalcone synthesis. a) 1 equiv. benzaldehyde 36, 5 mol % LiOH.H2O, abs. EtOH., conditions see table 3. [0371] Over the years, numerous basic (e.g. NaOH, Ba(OH)2 and Al2O3) and acid (e.g. dry HCl and BF3) catalysts have been proposed for this transformation. We considered the LiOH.H2O catalyzed protocol as proposed by Bhagat and co-workers to be the most elegant, because of its high catalyst turnover and yields, short reaction times and easy work-up. Nevertheless, as we could only obtain the high yields reported by these researchers after prolonged reaction times, we evaluated the influence of the reaction temperature on its outcome. As such, by rising the temperature to 40 or 70 C., and by optimizing the work-up procedure, we were able to obtain the pure chalcones 37-51 in reasonable to excellent yield after crystallization in ethanol (see table 3). [TABLE-US-00003] TABLE 3 Synthesis conditions and yield for the synthetic chalcones 37-51 in the training set. Reaction conditions Temperaturea Time Yieldb R R? ( C.) (h) (%) 37 H H 20 .83 74 38 4?-MeO H 20 2 80 39 H 4-MeO 20 3 77 40 4?-MeO 4-MeO 40 2 82 41 4?-MeO 3-MeO 20 1 62 42 2?,4?,6?-triMeO 2,4,5-triMeO 20 168 78 43 2?,4?,6?-triMeO 4-MeO 20 86 69 44 4?-MeO 2,4,5-triMeO 20 15 92 45 4?-MeO 2,4,6-triMeO 70 2 89 46 2?,6?-diMeO 2,4,5-triMeO 40 5.5 62 47 2?,6?-diMeO 2,4,6-triMeO 40 48 64 48 4?-MeO 4-F 20 4 91 49 3?,4?,5?-triMeO 4-F 20 24 69 50 4?-F 4-F 20 1 42 51 H 4-F 40 2 51 [0372] The synthesis of compounds 52-55 was conducted in a similar way as described above for compounds 37-51, and the synthesis conditions are as depicted in table 4. [TABLE-US-00004] TABLE 4 Synthesis conditions and yield for the synthetic chalcones 52-55. R R? Conditions Yielda (%) 52 4?-MeO 4-Cl r.t., 2 h 85 53 4?-F 3-F r.t., 1 h 15 min 70 54 4?-MeO 3-F r.t., 30 min 76 55 4?-MeO 2-F r.t., 4 h 88
64%	With lithium hydroxide monohydrate; In ethanol; at 40℃; for 48h;	General procedure: A solution of the acetophenone(10 mmol) and LiOH.H2O (10 mol%) in 10 mL of absoluteethanol is stirred at the appropriate temperature for 10 min (for reactions at40 C, the bulb is equipped with a reflux condenser). Then, the benzaldehyde(10 mmol, 1 equiv.) is added and the system is protected from theatmosphere with a cork stopper. Reaction progress is monitored by TLC orLCMS-analysis; during the course of the reaction, the chalcone may precipitate.Upon attaining maximum conversion grade, the reaction mixture is quenched with15 mL of 1% hydrochloric acid.If the chalcone has precipitated, it isisolated by means of filtration. In order to remove residual amounts ofbenzaldehyde, the residue is washed thoroughly with water until the filtrateturns clear. The obtained solid is the chalcone, which can be dried in adessicator. Subsequently, the chalcone can be recrystallized in absoluteethanol so as to obtain high purity crystals.If the chalcone has formed a separate oilyliquor at the bottom of the bulb, it can be extracted from the mixture withdiethyl ether. The organic phase is subsequently washed with brine (2x) anddried over MgSO4, upon which the solution is concentrated in vacuo. Again, purification of the thusobtained residue can be performed through recrystallization in absoluteethanol.Detailed reaction conditions and yields for chalcones 35-50are provided in Table S13
24%	With potassium hydroxide; In methanol; water; at 70℃; for 3h;	1 mM of 2,6-methoxyacetophenone and 1 mM of <strong>[830-79-5]2,4,6-trimethoxybenzaldehyde</strong> in 10 ml of methanol, in the presence of 1 ml of 25% KOH, were heated to 70 C. for 3 hours. The solvent is then evaporated under reduced pressure, water is added and the mixture is extracted with CH2Cl2. The organic phase is dried, evaporated. The obtained products are solids. Purification is carried out with chromatography by eluting with a (1:5) mixture of ethyl acetate and cyclohexane The chalcone is obtained with a yield of 24%. m.p.=170 C.

Reference： [1]Patent: US2015/11620,2015,A1 .Location in patent: Paragraph 0361-0363; 0369-0372
[2]European Journal of Medicinal Chemistry,2015,vol. 101,p. 627 - 639
[3]Journal of Medicinal Chemistry,2008,vol. 51,p. 2307 - 2310
[4]Patent: US2009/182058,2009,A1 .Location in patent: Page/Page column 5

19
[ 1466-76-8 ]
[ 75-05-8 ]
[ 2040-04-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With palladium(II) trifluoroacetate; 6-methyl-2,2'-bipyridine In water at 100℃; for 48h;
71%	With Pd⁽²⁺⁾*2C₅F₉O₂^(1-); trifluoroacetic acid; 6-methyl-2,2'-bipyridine In tetrahydrofuran; water at 130℃; for 0.5h; Microwave irradiation;	Procedure for the synthesis of ketones 3a, 3c,3d and 3e, Table 1 conditions [a] General procedure: A 5 mL microwave vialwas charged with 6-methyl-2,2'-bipyridine (16.3 mg, 0.096 mmol), Pd(O2CCF3)2(26.6 mg, 0.08 mmol) and 2 mL THF. After stirring at room temperature for 5minutes, 2,6-dimethoxy benzoic acid (182.2 mg, 1 mmol), nitrile (5 mmol), water(200 µL) and TFA (77 µL,1 mmol) were added and the mixture heated in the microwave for 30 minutes at130 °C. The mixture was diluted with DCM (15 mL) and0.1 M NaOH (15 mL, 3a) or 1% HCl (15mL, 3c, 3d and 3e), the phaseswere separated and extracted with DCM (2 ×15 mL), dried with Na2SO4, filtered and concentratedunder reduced pressure. Purification by flash chromatography afforded ketones 3a, 3c, 3d or 3e in the yields stated in Table 1.
49%	With [2,2]bipyridinyl; palladium(II) trifluoroacetate; water In neat (no solvent) at 130℃; for 0.5h; Microwave irradiation;

Reference： [1]Lindh, Jonas; Sjoeberg, Per J. R.; Larhed, Mats [Angewandte Chemie - International Edition, 2010, vol. 49, # 42, p. 7733 - 7737]
[2]Axelsson, Linda; Veron, Jean-Baptiste; Sävmarker, Jonas; Lindh, Jonas; Odell, Luke R.; Larhed, Mats [Tetrahedron Letters, 2014, vol. 55, # 15, p. 2376 - 2380]
[3]Svensson, Fredrik; Mane, Rajendra S.; Saevmarker, Jonas; Larhed, Mats; Skoeld, Christian [Organometallics, 2013, vol. 32, # 2, p. 490 - 497]

20
[ 528-75-6 ]
[ 2040-04-2 ]
[ 1365644-16-1 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 2,6-dimethoxyacetophenone With lithium hydroxide monohydrate In ethanol at 20℃; for 0.166667h; Stage #2: 2,4-dinitrobenzaldehyde In ethanol at 20℃; for 2h;	General procedure for synthesis of chalcones General procedure: In a 14-ml vial, the substituted acetophenone (1.25 mmol) and lithium hydroxide monohydrate (0.251 mmol) were dissolved in ethanol (5 mL) and the mixture was stirred at RT for 10 min followed by addition of substituted benzaldehyde (1.272 mmol). The reaction mixture was then stirred at RT and monitored by TLC using 25% ethyl acetate/hexanes as the solvent system. The reaction was quenched after 2 hr by pouring into 50 ml of stirring ice cold water. If the product precipitated out after quenching with cold water, it was filtered off and crystallized with hot ethanol. In some examples, a sticky mass was observed in the aqueous solution after quenching. In those cases, the product was extracted by ethyl acetate (3 x 50 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexanes as the solvent system in increasing order of polarity. Chalcones 1a- 1j, 2a- 2j, 3a- 3j, 4a- 4j, 5a- 5j, 6a-e, 6g-h, 6i, 7a-h, 7j, 8a, 9a, 9d-e, 9i, 10a-b, 10d-e, 10h-j have been reported earlier in the literature.1-32 To the best of our knowledge, there is no literature available for rest of the chalcones. The characterization data of these chalcone derivatives i.e. 1H, 13C NMR, LC-MS-TOF and purity analysis are given in subsequent sections.

Reference： [1]Kim, Yeong Sang; Kumar, Vineet; Lee, Sunmin; Iwai, Aki; Neckers, Len; Malhotra, Sanjay V.; Trepel, Jane B. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2105 - 2109]

21
[ 2040-04-2 ]
[ 24964-64-5 ]
[ 1365644-27-4 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 2,6-dimethoxyacetophenone With lithium hydroxide monohydrate In ethanol at 20℃; for 0.166667h; Stage #2: 3-Cyanobenzaldehyde In ethanol at 20℃; for 2h;	General procedure for synthesis of chalcones General procedure: In a 14-ml vial, the substituted acetophenone (1.25 mmol) and lithium hydroxide monohydrate (0.251 mmol) were dissolved in ethanol (5 mL) and the mixture was stirred at RT for 10 min followed by addition of substituted benzaldehyde (1.272 mmol). The reaction mixture was then stirred at RT and monitored by TLC using 25% ethyl acetate/hexanes as the solvent system. The reaction was quenched after 2 hr by pouring into 50 ml of stirring ice cold water. If the product precipitated out after quenching with cold water, it was filtered off and crystallized with hot ethanol. In some examples, a sticky mass was observed in the aqueous solution after quenching. In those cases, the product was extracted by ethyl acetate (3 x 50 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexanes as the solvent system in increasing order of polarity. Chalcones 1a- 1j, 2a- 2j, 3a- 3j, 4a- 4j, 5a- 5j, 6a-e, 6g-h, 6i, 7a-h, 7j, 8a, 9a, 9d-e, 9i, 10a-b, 10d-e, 10h-j have been reported earlier in the literature.1-32 To the best of our knowledge, there is no literature available for rest of the chalcones. The characterization data of these chalcone derivatives i.e. 1H, 13C NMR, LC-MS-TOF and purity analysis are given in subsequent sections.

Reference： [1]Kim, Yeong Sang; Kumar, Vineet; Lee, Sunmin; Iwai, Aki; Neckers, Len; Malhotra, Sanjay V.; Trepel, Jane B. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2105 - 2109]

22
[ 2040-04-2 ]
[ 99-61-6 ]
[ 1365643-99-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: 2,6-dimethoxyacetophenone With lithium hydroxide monohydrate In ethanol at 20℃; for 0.166667h; Stage #2: 3-nitro-benzaldehyde In ethanol at 20℃; for 2h;	General procedure for synthesis of chalcones General procedure: In a 14-ml vial, the substituted acetophenone (1.25 mmol) and lithium hydroxide monohydrate (0.251 mmol) were dissolved in ethanol (5 mL) and the mixture was stirred at RT for 10 min followed by addition of substituted benzaldehyde (1.272 mmol). The reaction mixture was then stirred at RT and monitored by TLC using 25% ethyl acetate/hexanes as the solvent system. The reaction was quenched after 2 hr by pouring into 50 ml of stirring ice cold water. If the product precipitated out after quenching with cold water, it was filtered off and crystallized with hot ethanol. In some examples, a sticky mass was observed in the aqueous solution after quenching. In those cases, the product was extracted by ethyl acetate (3 x 50 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexanes as the solvent system in increasing order of polarity. Chalcones 1a- 1j, 2a- 2j, 3a- 3j, 4a- 4j, 5a- 5j, 6a-e, 6g-h, 6i, 7a-h, 7j, 8a, 9a, 9d-e, 9i, 10a-b, 10d-e, 10h-j have been reported earlier in the literature.1-32 To the best of our knowledge, there is no literature available for rest of the chalcones. The characterization data of these chalcone derivatives i.e. 1H, 13C NMR, LC-MS-TOF and purity analysis are given in subsequent sections.

Reference： [1]Kim, Yeong Sang; Kumar, Vineet; Lee, Sunmin; Iwai, Aki; Neckers, Len; Malhotra, Sanjay V.; Trepel, Jane B. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2105 - 2109]

23
[ 2040-04-2 ]
[ 105-07-7 ]
[ 1365644-39-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 2,6-dimethoxyacetophenone With lithium hydroxide monohydrate In ethanol at 20℃; for 0.166667h; Stage #2: 4-cyanobenzaldehyde In ethanol at 20℃; for 2h;	General procedure for synthesis of chalcones General procedure: In a 14-ml vial, the substituted acetophenone (1.25 mmol) and lithium hydroxide monohydrate (0.251 mmol) were dissolved in ethanol (5 mL) and the mixture was stirred at RT for 10 min followed by addition of substituted benzaldehyde (1.272 mmol). The reaction mixture was then stirred at RT and monitored by TLC using 25% ethyl acetate/hexanes as the solvent system. The reaction was quenched after 2 hr by pouring into 50 ml of stirring ice cold water. If the product precipitated out after quenching with cold water, it was filtered off and crystallized with hot ethanol. In some examples, a sticky mass was observed in the aqueous solution after quenching. In those cases, the product was extracted by ethyl acetate (3 x 50 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexanes as the solvent system in increasing order of polarity. Chalcones 1a- 1j, 2a- 2j, 3a- 3j, 4a- 4j, 5a- 5j, 6a-e, 6g-h, 6i, 7a-h, 7j, 8a, 9a, 9d-e, 9i, 10a-b, 10d-e, 10h-j have been reported earlier in the literature.1-32 To the best of our knowledge, there is no literature available for rest of the chalcones. The characterization data of these chalcone derivatives i.e. 1H, 13C NMR, LC-MS-TOF and purity analysis are given in subsequent sections.

Reference： [1]Kim, Yeong Sang; Kumar, Vineet; Lee, Sunmin; Iwai, Aki; Neckers, Len; Malhotra, Sanjay V.; Trepel, Jane B. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2105 - 2109]

24
[ 2040-04-2 ]
[ 105-07-7 ]
[ 1365644-40-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 2,6-dimethoxyacetophenone With lithium hydroxide monohydrate In ethanol at 20℃; for 0.166667h; Stage #2: 4-cyanobenzaldehyde In ethanol at 20℃; for 2h;	General procedure for synthesis of chalcones General procedure: In a 14-ml vial, the substituted acetophenone (1.25 mmol) and lithium hydroxide monohydrate (0.251 mmol) were dissolved in ethanol (5 mL) and the mixture was stirred at RT for 10 min followed by addition of substituted benzaldehyde (1.272 mmol). The reaction mixture was then stirred at RT and monitored by TLC using 25% ethyl acetate/hexanes as the solvent system. The reaction was quenched after 2 hr by pouring into 50 ml of stirring ice cold water. If the product precipitated out after quenching with cold water, it was filtered off and crystallized with hot ethanol. In some examples, a sticky mass was observed in the aqueous solution after quenching. In those cases, the product was extracted by ethyl acetate (3 x 50 mL), dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexanes as the solvent system in increasing order of polarity. Chalcones 1a- 1j, 2a- 2j, 3a- 3j, 4a- 4j, 5a- 5j, 6a-e, 6g-h, 6i, 7a-h, 7j, 8a, 9a, 9d-e, 9i, 10a-b, 10d-e, 10h-j have been reported earlier in the literature.1-32 To the best of our knowledge, there is no literature available for rest of the chalcones. The characterization data of these chalcone derivatives i.e. 1H, 13C NMR, LC-MS-TOF and purity analysis are given in subsequent sections.

Reference： [1]Kim, Yeong Sang; Kumar, Vineet; Lee, Sunmin; Iwai, Aki; Neckers, Len; Malhotra, Sanjay V.; Trepel, Jane B. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2105 - 2109]

25
[ 830-79-5 ]
[ 2040-04-2 ]
[ 1017262-80-4 ]

Yield	Reaction Conditions	Operation in experiment
24%	With potassium hydroxide In ethanol; water at 60℃;
	With potassium hydroxide In methanol at 90℃; for 24h;	5.3. General procedure for the synthesis of chalcones 1-19 General procedure: The acetophenone (10 mmol) and the benzaldehyde derivatives(1 eq.) were solubilized in methanol (200 mL). Potassium hydroxide(10 mL, 50%) was added and the solution was stirred at 90 °C for24 h. The solution was evaporated to dryness and the residue was suspended in H2O. The solid formed was filtered, washed with H2O then dried in oven at 40 °C and reduced pressure to give the desired chalcone as yellow pale solids which were fully characterized byNMR and mass spectrometry analyses.

Reference： [1]Location in patent: scheme or table Valdameri, Glaucio; Gauthier, Charlotte; Terreux, Raphaël; Kachadourian, Rémy; Day, Brian J.; Winnischofer, Sheila M. B.; Rocha, Maria E. M.; Frachet, Véronique; Ronot, Xavier; Di Pietro, Attilio; Boumendjel, Ahcène [Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3193 - 3200]
[2]Dumontet, Charles; Beck, Guillaume; Gardebien, Fabrice; Haudecoeur, Romain; Mathé, Doriane; Matera, Eva-Laure; Tourette, Anne; Mattei, Eve; Esmenjaud, Justine; Boyère, Cédric; Nurisso, Alessandra; Peuchmaur, Marine; Pérès, Basile; Bouchaud, Grégory; Magnan, Antoine; Monneret, Guillaume; Boumendjel, Ahcène [European Journal of Medicinal Chemistry, 2018, vol. 158, p. 405 - 413]

26
[ 2040-04-2 ]
[ 591-31-1 ]
[ 1017262-76-8 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium hydroxide In ethanol; water at 60℃;
	With potassium hydroxide In methanol at 90℃; for 24h;	5.3. General procedure for the synthesis of chalcones 1-19 General procedure: The acetophenone (10 mmol) and the benzaldehyde derivatives(1 eq.) were solubilized in methanol (200 mL). Potassium hydroxide(10 mL, 50%) was added and the solution was stirred at 90 °C for24 h. The solution was evaporated to dryness and the residue was suspended in H2O. The solid formed was filtered, washed with H2O then dried in oven at 40 °C and reduced pressure to give the desired chalcone as yellow pale solids which were fully characterized byNMR and mass spectrometry analyses.

Reference： [1]Location in patent: scheme or table Valdameri, Glaucio; Gauthier, Charlotte; Terreux, Raphaël; Kachadourian, Rémy; Day, Brian J.; Winnischofer, Sheila M. B.; Rocha, Maria E. M.; Frachet, Véronique; Ronot, Xavier; Di Pietro, Attilio; Boumendjel, Ahcène [Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3193 - 3200]
[2]Dumontet, Charles; Beck, Guillaume; Gardebien, Fabrice; Haudecoeur, Romain; Mathé, Doriane; Matera, Eva-Laure; Tourette, Anne; Mattei, Eve; Esmenjaud, Justine; Boyère, Cédric; Nurisso, Alessandra; Peuchmaur, Marine; Pérès, Basile; Bouchaud, Grégory; Magnan, Antoine; Monneret, Guillaume; Boumendjel, Ahcène [European Journal of Medicinal Chemistry, 2018, vol. 158, p. 405 - 413]

27
[ 2040-04-2 ]
[ 3392-97-0 ]
[ 346670-54-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium hydroxide In ethanol; water at 60℃;
	With potassium hydroxide In methanol at 90℃; for 24h;	5.3. General procedure for the synthesis of chalcones 1-19 General procedure: The acetophenone (10 mmol) and the benzaldehyde derivatives(1 eq.) were solubilized in methanol (200 mL). Potassium hydroxide(10 mL, 50%) was added and the solution was stirred at 90 °C for24 h. The solution was evaporated to dryness and the residue was suspended in H2O. The solid formed was filtered, washed with H2O then dried in oven at 40 °C and reduced pressure to give the desired chalcone as yellow pale solids which were fully characterized byNMR and mass spectrometry analyses.

Reference： [1]Location in patent: scheme or table Valdameri, Glaucio; Gauthier, Charlotte; Terreux, Raphaël; Kachadourian, Rémy; Day, Brian J.; Winnischofer, Sheila M. B.; Rocha, Maria E. M.; Frachet, Véronique; Ronot, Xavier; Di Pietro, Attilio; Boumendjel, Ahcène [Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3193 - 3200]
[2]Dumontet, Charles; Beck, Guillaume; Gardebien, Fabrice; Haudecoeur, Romain; Mathé, Doriane; Matera, Eva-Laure; Tourette, Anne; Mattei, Eve; Esmenjaud, Justine; Boyère, Cédric; Nurisso, Alessandra; Peuchmaur, Marine; Pérès, Basile; Bouchaud, Grégory; Magnan, Antoine; Monneret, Guillaume; Boumendjel, Ahcène [European Journal of Medicinal Chemistry, 2018, vol. 158, p. 405 - 413]

28
[ 93-58-3 ]
[ 2040-04-2 ]
[ 1402815-87-5 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 2,6-dimethoxyacetophenone With sodium hydride In tetrahydrofuran at 5 - 10℃; Stage #2: benzoic acid methyl ester In tetrahydrofuran for 6h; Reflux;	General procedure for synthesis of compounds 2, 9, 11, 18 General procedure: Mixture of sodium hydride (0.20 mole for 2, 9, 11, 0.30 mole for 18) and THF (72g, 82ml) was cooled to 5°C, and the substituted acetophenone (0.10 mole) was added dropwise keeping the temperature below 10°C and rapid stirring. Next, methyl benzoate (0.20 mole) was added, and the mixture was warmed up to the boiling point and refluxed for 6 hours. After cooling down to 5°C,the mixture was poured on crushed ice (200g), and 10% solution of hydrochloric acid was added until neutral pH. Separated aqueous layer was extracted with methylene chloride, and combined organic layers were rinsed with 5% solution of sodium bicarbonate, next with water and dried with anhydrous magnesium sulfate. After filtering the drying agent, solution was concentrated on vacuum rotary evaporator, filtered and crystalized from ethanol.

Reference： [1]Zawadiak, Jan; Mrzyczek, Marek [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2012, vol. 96, p. 815 - 819]

29
[ 2040-04-2 ]
[ 1422526-44-0 ]
[ 1422526-50-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium hydroxide In water at 0 - 20℃;	1 General procedure for the preparation of quinolinyl chalcones 6a-e and 8-16 General procedure: Compound 5 (0.53 g, 2.0 mmol) and appropriate acetophenone (2.0 mmol) were stirred at 0 °C for 15 min. Aqueous solution of KOH (6 equiv) was added and the mixture was stirred at room temperature for 12 h (TLC monitoring). After the reaction reached completion, the resulting mixture was added 1 M HCl until pH 3 resulted and extracted with ethyl acetate (50 mL × 3). The organic layer was collected, dried over MgSO4 and concentrated in vacuo. The crude product was purified and crystallized with EtOH to give quinolinyl chalcones 6a-i and 8-16.

Reference： [1]Tseng, Chih-Hua; Chen, Yeh-Long; Hsu, Chih-Yao; Chen, Tzu-Chiang; Cheng, Chih-Mei; Tso, Hsien-Cheng; Lu, Yan-Jia; Tzeng, Cherng-Chyi [European Journal of Medicinal Chemistry, 2013, vol. 59, p. 274 - 282]

30
[ 2040-04-2 ]
[ 95-92-1 ]
[ 1443991-21-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium In ethanol at 20℃; for 6h;	3.7. Ethyl 4-(2,6-dimethoxyphenyl)-4-hydroxy-2-oxobut-3-enoate (19) Sodium (11.4g, 496mmol) was dissolved in EtOH (450mL) using an ice bath to control the exotherm. To this solution, diethyl oxalate (45mL, 332mmol) was added in one portion, followed by a slurry of 2′,6′-dimethoxyacetophenone (30.0g, 166mmol) in EtOH (250mL). The resulting suspension was allowed to stir at ambient temperature for 6h then the solvent removed in vacuo. The mixture was extracted with EtOAc (8×350mL) ensuring the pH remained below 6 between each extraction (addition of concd hydrochloric acid). The organic phases were combined, dried (MgSO4), and the solvent removed in vacuo. Following recrystallisation from EtOH, the title compound was as a glassy crystalline solid (41.2g, 147mmol, 88% yield).Mp: 102-104°C;1H NMR (400MHz, CDCl3): 14.33 (1H, br s, OH), 7.34 (1H, t,J=8.4Hz, H-1), 6.60 (1H, s, H-6), 6.59 (1H, d,J=8.4Hz, H-2), 4.35 (2H, q,J=7.1Hz, H-1′), 3.82 (6H, s, H-3′), 1.37 (3H, t,J=7.1Hz);13C NMR (100MHz, CDCl3): 195.8 (C-5), 164.0 (C-7), 162.6 (C-8), 158.0 (C-3), 132.4 (C-1), 117.2 (C-4), 106.4 (C-6), 104.3 (C-2), 62.5 (C-1′), 56.2 (C-3′), 14.2 (C-2′); LC-MS:Rt=4.19, [MNa]+=302.83; IR (neat) cm-1: 1735.7 (m), 1625.1 (m), 1586.8 (s), 1475.3 (m), 1257.5 (s); HRMS: calcd for [C14H16O6Na]+=303.0845, found 303.0847,Δ=0.7ppm; Microanalysis: calcd (found) for C14H16O6; C=59.99% (59.99%), H=5.75% (5.72%), N=0.00% (0.00%); The structure was unambiguously confirmed by X-ray crystallography and the structure deposited at the CCDC with the unique reference 913971.

Reference： [1]Baxendale; Cheung; Kitching; Ley; Shearman [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 14, p. 4378 - 4387]

31
[ 2040-04-2 ]
[ 105-58-8 ]
[ 125732-13-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydride In toluene at 20 - 110℃; for 1h; Inert atmosphere;
78%	With sodium hydride In toluene; mineral oil	1 General procedure for the synthesis of benzoylacetates 10 a-n General procedure: The substrate b-ketoesters 10 a-n were either purchased or synthesized following published procedures. Some benzoylacetates were commercially available. Ethyl 3-oxo-3-phenyl propanoate (10a) was purchased. The reaction of benzoylacetates 10 b-n was prepared as described in previous reports. 25-27 A solution of a substituted acetophenone 8 a-n (0.05 mol) dissolved in toluene (50 mL) was added dropwise to a solution containing diethyl carbonate (9) (0.10 mol) and sodium hydride (0.15 mol 60% dispersion in mineral oil). The mixture was stirred at room temperature, and then refluxed for 30 min. The mixture was poured into ice water,acidified with glacial acetic acid, and extracted with EtOAc (3x100 mL). The EtOAc extract was then dried over anhydrous MgSO4. After removal of the solvent in vacuo, the crude products were purified by silica gel column chromatography eluting with dichloromethane to afford benzoylacetates 10 b-n. All synthetic compounds were in agreement with 1H NMR, 13C NMR, IR and mass spectroscopic data.

Reference： [1]Kundu, Kshama; Nayak, Sandip K. [Journal of Natural Products, 2017, vol. 80, # 6, p. 1776 - 1782]
[2]Chen, Yi-Fong; Lin, Yi-Chien; Huang, Po-Kai; Chan, Hsu-Chin; Kuo, Sheng-Chu; Lee, Kuo-Hsiung; Huang, Li-Jiau [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5064 - 5075]

32
[ 504-29-0 ]
[ 2040-04-2 ]
2-(2,6-dimethoxyphenyl)imidazo[1,2-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With copper(l) iodide; boron trifluoride diethyl etherate; oxygen In N,N-dimethyl-formamide at 60℃; for 24h;
	With copper(l) iodide; boron trifluoride diethyl etherate In N,N-dimethyl-formamide at 60℃; for 24h;	Typical Procedure for the Synthesis of 2- Phenylimidazo[1,2-a]pyridine (3a) General procedure: 470 mg (5.0 mmol) of 2-aminopyridine 1a, 1200 mg (10 mmol) of acetophenone 2a, CuI 5 mol% (47 mg; 0.25 mmol), BF3·Et2O (45-50% purity); 10 mol%, 0.5 mmol) and DMF (2 mL) were placed in a 25-mL double-necked round-bottomed flask. The mixture was heated in an oil bath at 60 oC for 24 h under an oxygen atmosphere (balloon). After completion of the reaction, it was allowed to attain to room temperature and then the mixture was poured into 20 mL of sodium carbonate solution. The product was extracted with DCM (50 mL 3) and dried with anhydrous Na2SO4. Removal of the solvent under reduced pressure left a residue that was purified through column chromatography using silica gel (30% EtOAc/hexane) to afford 3a; yield: 0.799 g (82%).

Reference： [1]Mohan, Darapaneni Chandra; Donthiri, Ramachandra Reddy; Rao, Sadu Nageswara; Adimurthy, Subbarayappa [Advanced Synthesis and Catalysis, 2013, vol. 355, # 11-12, p. 2217 - 2221]
[2]Chitrakar, Ravi; Rawat, Deepa; Sistla, Ramakrishna; Subbarayappa, Adimurthy; Vadithe, Lakshma Nayak [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 49]

33
[ 99501-03-8 ]
[ 2040-04-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With acetone In toluene at 80℃; for 0.25h; Flow reactor;
72%	With C₃₅H₂₈Cl₂N₅PRu; potassium <i>tert</i>-butylate In toluene at 50℃; for 6h; chemoselective reaction;	2.5. Procedure for catalytic alcohol oxidation reaction General procedure: using the complex 1 as catalyst in presence of a base following a general procedure. In a round-bottom flask, 1 mmol of substrate, 0.005mmol of catalyst (3.6mg) and 0.010 mmol of tBuOK (1.1mg) were mixed in 10mL toluene. The reaction mixture was heated at 50°C in aerobic condition with continuous stirring for 6h and then the solvent was evaporated with a rotary evaporator under reduced pressure. The crude product, thus obtained, was purified on preparative silica gel GF-254 TLC plate using ethyl acetate: hexane (1:10) solvent mixture as eluent. The oxidized products were characterized by NMR spectroscopy (See Figs. S4-S32).
	With chromium(VI) oxide 2,6-Dimethoxy-benzoylchlorid, Dimethylcadmium;

Reference： [1]Chorghade, Rajeev; Battilocchio, Claudio; Hawkins, Joel M.; Ley, Steven V. [Organic Letters, 2013, vol. 15, # 22, p. 5698 - 5701]
[2]Saha, Tanushri; Pramanick, Rajib; Sengupta, Debabrata; Goswami, Sreebrata [Inorganica Chimica Acta, 2019, vol. 484, p. 160 - 166]
[3]Dhami,K.S.; Stothers,J.B. [Canadian Journal of Chemistry, 1965, vol. 43, p. 479]

34
[ 126829-31-0 ]
[ 2040-04-2 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 948 - 951

35
[ 16932-44-8 ]
[ 2040-04-2 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 948 - 951

36
[ 2040-04-2 ]
[ 75-16-1 ]
[ 16929-70-7 ]

Yield	Reaction Conditions	Operation in experiment
76%	In tetrahydrofuran at 0 - 20℃; for 16h;	INTERMEDIATE 1-41: 2-(2,6-dimethoxyphenyl)propan-2-ol To a solution of l-(2,6-dimethoxyphenyl)ethanone (5.0 g, 27.75 mmol) in THF (50mL) was added methylmagnesium bromide 3M in THF (37. mL, 111.0 mmol) dropwise at 0°C. The reaction mixture was stirred for 16 h at room temperature. The mixture was quenched at 0°C with a saturated aqueous solution of NH4Cl and extracted with AcOEt (3 x 50 mL). The organic layers were washed with water and brine, dried over Na2S04, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of ethyl acctatcxyclohcxanc - 0:100 to 80:20 to afford the title compound as a yellow oil (4.4 g, 76% yield). 1H NMR (300MHz, DMSO-d6) 7.15 (t, J = 8.4 Hz, 1H), 6.68 (d, J = 8.4 Hz, 2H), 5.42 (s, 1H), 3.76 (s, 6H), 1.50 (s, 6H)
75%	In tetrahydrofuran at 0 - 20℃; for 16h;	6 To a solution of l-(2,6-dimethoxyphenyl)ethanone (50.0g, 277.8mmol) in THF (500mL) is added MeMgBr (370.4mL, 1111.2mmol, 3.0M) dropwise at 0°C. The reaction mixture is stirred for 16h at rt. The mixture is quenched with aqueous solution of NH4C1 at 0°C and extracted with EA (200*3mL). The organic layers are washed with water and brine, dried over Na2S04, filtered, and concentrated. The resulting oil is purified by silica gel column chromatography using PE: EA =20: 1 as eluent to give the desired product (40.8g, yield 75%) as yellow oil.
75%	In tetrahydrofuran at 0 - 20℃; for 16h;	13.2 Step2: Preparation -(2, 6-dimethoxyphenyl)propan-2-ol To a solution of l-(2,6-dimethoxyphenyl)ethanone (25.0 g, 138.9 mmol) in THF (250 mL) was added MeMgBr (3 M in THF, 185.2 mL, 555.6 mmol) dropwise at 0 °C. The reaction mixture was stirred for 16 h at room temperature. The mixture was quenched by solution of NH4C1 at 0 °C and extracted with EA (100 x 3mL). The organic layers were washed with water and brine, dried over Na2S04, filtered, and concentrated. The resulting oil was purified by silica gel column chromatography using PE:EA = 20: 1 as an eluent to give 2-(2,6-dimethoxyphenyl)propan-2-ol (20.4 g, yield 75%) as a yellow oil. MS: m/z = 179.0 (M-OH, ESI+).

Reference： [1]Current Patent Assignee: BIONOMICS LIMITED - WO2020/65, 2020, A2 Location in patent: Page/Page column 95
[2]Current Patent Assignee: ELI LILLY & CO; PFIZER INC - WO2014/149793, 2014, A1 Location in patent: Page/Page column 51
[3]Current Patent Assignee: PFIZER INC - WO2015/13318, 2015, A1 Location in patent: Paragraph 0245

37
[ 98-01-1 ]
[ 2040-04-2 ]
(2E)-1-(2,6-dimethoxyphenyl)-3-(furan-2-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With lithium hydroxide monohydrate In ethanol at 40℃; for 76h;	B.B.1 General procedure: The synthesis of compounds 68-70 and 72-79 was conducted as schematically represented below and further detailed in table 6. wherein R is as represented in table 6. Scheme: [0376] Synthesis of furyl chalcones. 1 equiv. aldehyde, 10 mol % LiOH.H2O, abs. EtOH, 40° C., Reaction conditions see table 6 [TABLE-US-00006] TABLE 6 Synthesis of furyl chalcones 68-70 and 72-79. R Aldehyde Time (h) Yield (%) 68 - 67a 7 76 69 - 67b 7 15a 70 - 67c 6 91a 72 H 67c 70 94 73 4′-F 67c 5 82 74 4′-MeO 67c 5 98 75 3′,4′,5′-triMeO 67c 5 56a 76 2′,6′-diMeO 67c 76 31b 77 4′-F 67d 19 30a 78 4′-F 67e 20 10 79 4′-MeO 67e 18 82
31%	With lithium hydroxide monohydrate In ethanol at 40℃; for 76h;

Reference： [1]Current Patent Assignee: GHENT UNIVERSITY - US2015/11620, 2015, A1 Location in patent: Paragraph 0375; 0376
[2]Roman, Bart I.; De Ryck, Tine; Patronov, Atanas; Slavov, Svetoslav H.; Vanhoecke, Barbara W.A.; Katritzky, Alan R.; Bracke, Marc E.; Stevens, Christian V. [European Journal of Medicinal Chemistry, 2015, vol. 101, p. 627 - 639]

38
[ 2040-04-2 ]
[ 100-63-0 ]
2-(2,6-dimethoxyphenyl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With phosphoric acid at 20 - 110℃; for 2.58333h;
43%	Stage #1: 2,6-dimethoxyacetophenone; phenylhydrazine With phosphoric acid at 20℃; for 0.5h; Stage #2: at 80 - 110℃; for 2.25h;	3 In a 100 ml round bottom flask, 9.0 g of 2 ', 6'-dimethoxyacetophenone (50 mmol) and 7.1 were added Ml phenylhydrazine (60 mmol), Then slowly add 10 ml of phosphoric acid, And stirred at room temperature for 0.5 hour evenly. Then slowly add 50 grams of polyphosphoric acid. With the progress of the reaction, the system has obvious heat release. The mixture was then heated to 80 ° C for 0.75 hours, then heated to 110 ° C and held at 110 ° C for 1.5 hours. The mixture was poured into ice water and the reaction was stopped. 200 mL of methylene chloride was added to the system and extracted with 200 mL of methylene chloride in three separate additions. The organic phases were combined and dried over anhydrous sodium sulfate. After depressurizing all the solution, The concentrated reaction mixture was purified by column chromatography to give the product as a light yellow powder. The product is then recrystallized and filtered with hot ethanol and water, 5.5 g of the pure 2- (2,6-dimethoxyphenyl) -1H-indole intermediate as a white crystalline product was obtained, Yield 43%.
43%	Stage #1: 2,6-dimethoxyacetophenone; phenylhydrazine With phosphoric acid at 20℃; for 0.333333h; Stage #2: at 80 - 110℃; for 2.25h;

Reference： [1]Fu, Wai Chung; So, Chau Ming; Chow, Wing Kin; Yuen, On Ying; Kwong, Fuk Yee [Organic Letters, 2015, vol. 17, # 18, p. 4612 - 4615]
[2]Current Patent Assignee: HONG KONG POLYTECHNIC UNIVERSITY - CN107445991, 2017, A Location in patent: Paragraph 0187-0188
[3]Choy, Pui Ying; Yuen, On Ying; Leung, Man Pan; Chow, Wing Kin; Kwong, Fuk Yee [European Journal of Organic Chemistry, 2020, vol. 2020, # 19, p. 2846 - 2853]

39
[ 2040-04-2 ]
[ 95-92-1 ]
ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium ethanolate In ethanol at 20℃; for 4.5h; Reflux;	157.1 Step 1: Preparation of ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate Step 1: Preparation of ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate: To a solution of sodium ethoxide (21 % in EtOH) (5.4 mL, 14.37 mmol) was added dropwise a mixture of diethyl oxalate (1.85 mL, 13.690 mmol) and 2,6-dimethoxy acetophenone (2.45 g, 13.690 mmol) in anhydrous ethanol (15 mL). The resultant mixture was stirred at room temperature for 30 minutes, upon which yellow suspension formed. The reaction mixture was heated to reflux for 4 h. The reaction was cooled to room temperature. Ethanol was evaporated in vacuo. The resultant residue was triturated with diethyl ether (30 mL) and filtered to obtain sodium salt of ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate as yellow solid (4.0 g, 97 %). MS m/z: Calcd. for CwHieOe 280.09 [M]+, found 279.3 [M-H]+. H
	With sodium ethanolate In ethanol at 20℃; for 4.5h; Inert atmosphere; Reflux;	5.1.1. Ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate (40) To a solution of sodium ethoxide (21% in EtOH) (5.4 mL,14.37 mmol) was added dropwise a mixture of diethyl oxalate(1.85 mL, 13.690 mmol) and 2,6-dimethoxy acetophenone (2.45 g,13.69 mmol) in anhydrous ethanol (15 mL). The resultant mixture wasstirred at room temperature for 30 min, upon which yellow suspensionformed. The reaction mixture was heated to reflux for 4 h. The reactionwas cooled to room temperature. Ethanol was evaporated in vacuo. Theresultant residue was triturated with diethyl ether (30 mL) and filteredto obtain sodium salt of ethyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoateas yellow solid (4.0 g, 97%). MS (ESI) m/z: Calcd. for C14H16O6280.09 [M]+, found 279.3 [M-H]-.

Reference： [1]Current Patent Assignee: RESEARCH TRIANGLE INSTITUTE - WO2015/188073, 2015, A1 Location in patent: Paragraph 00122
[2]Maitra, Rangan; Narayanan, Sanju; Rajagopal, Sudarshan; Runyon, Scott P.; Vasukuttan, Vineetha [Bioorganic and medicinal chemistry, 2020]

40
[ 12093-10-6 ]
[ 2040-04-2 ]
3-ferrocenyl-1-(2,5-dimethoxyphenyl)-2-propen-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium hydroxide In ethanol at 25℃;	General procedure for the preparation of ferrocenylchalcones (1-18): General procedure: The substituted ketone (3 mmol) and KOH(0.2 g) were dissolved in ethanol (5 mL) in a round bottomedflask and stirred at room temperature (25 C) for 10 min. Anethanolic solution of the substituted aromatic aldehyde (3 mmol,5 mL) was added drop wise and the mixture was stirred at roomtemperature. The progress of the reaction was monitored by TLCon silica gel sheets. The reaction was stopped by neutralizingthe stirred solution with 2 M HCl. In most of the cases the productwas obtained as a dark red precipitate after neutralization. It wasthen removed by filtration, washed with water. In the absence ofa precipitate on neutralization, the solution was extracted withethyl acetate (20 mL × 3). The organic layer was dried overanhydrous sodium sulphate and removed by evaporation underreduced pressure to give a liquid residue. The latter was passedthrough a column of silica gel (230-400 mesh) and eluted withTHF-hexane (1:4) to yield pure compound. All the synthesizedcompounds were well characterized by spectroscopic methodssuch as IR, NMR, Mass and elemental analysis and their spectralcharacteristics were found to be in good general agreement withthose found in literature30.

Reference： [1]Mukhtar, Sayeed; Manasreh, Waleed Atef; Parveen, Humaira; Azam, Amir [Asian Journal of Chemistry, 2014, vol. 26, # 24, p. 8407 - 8412]

41
[ 2040-04-2 ]
[ 5123-13-7 ]
1-(3-methoxy[1,1′-biphenyl]-2-yl)ethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With styrene; carbonylchlorohydridobis(triisopropylphosphine)ruthenium(II); cesium fluoride In toluene at 80℃; for 0.25h; Glovebox; Inert atmosphere; Sealed tube;
7%	With styrene; tri-tert-butyl phosphine; (Carbonyl)dichloro(p-cymol)ruthenium(II); cesium fluoride In toluene at 100℃; for 1h; Sealed tube; Glovebox;

Reference： [1]Kondo, Hikaru; Kochi, Takuya; Kakiuchi, Fumitoshi [Organic Letters, 2017, vol. 19, # 4, p. 794 - 797]
[2]Kondo, Hikaru; Kochi, Takuya; Kakiuchi, Fumitoshi [Chemistry - A European Journal, 2020, vol. 26, # 8, p. 1737 - 1741]

42
[ 2040-04-2 ]
[ 380481-66-3 ]
1-(3-methoxy-4′-methyl[1,1′-biphenyl]-2-yl)ethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With styrene; carbonylchlorohydridobis(triisopropylphosphine)ruthenium(II); cesium fluoride In toluene at 80℃; for 0.25h; Glovebox; Inert atmosphere; Sealed tube;

Reference： [1]Kondo, Hikaru; Kochi, Takuya; Kakiuchi, Fumitoshi [Organic Letters, 2017, vol. 19, # 4, p. 794 - 797]

43
[ 2040-04-2 ]
[ 501374-30-7 ]
1-(3-methoxy-4′-[trifluoromethyl][1,1′-biphenyl]-2-yl)ethan-1-one [ No CAS ]