Name: 122334-37-6|4-Chloro-N-methoxy-N-methylbenzamide|97%
Brand: Ambeed
SKU: A197269
Price: 9.0 USD
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Rating: 97 (27 reviews)

1
[ 6638-79-5 ]
[ 74-11-3 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In methanol at 20℃; for 0.5h;
99%	Stage #1: para-chlorobenzoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 0℃; for 0.5h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 0 - 20℃;	2 Representative standard procedures for the synthesis of Weinreb amides 11 General procedure: In a solution of carboxylic acid (5 mmol) in DCM (10 mL) was added 1,l0-carbonyldiimidazole (CDI) (5 mmol) in DCM (2 mL) at 0 C. After stirring for 0.5 h, a N,O-dimethylhydroxylamine hydrochloride (5 mmol) was added to the mixture portion wise, followed by Et3N (5 mmol) dropwise at 0 C. The solution was stirred 1 h at 0 C and overnight at room temperature. The reaction mixture was washed with an aqueous solution of HC1 (1 N), a saturated aqueous solution of Na2CO3 and brine. The organic phase was dried over MgSO4, filtered, and concentrated under vacuum. The obtained residue was purified by column chromatography on silica gel(petroleum ether/EtOAc) to offer the pure amide 11. 4.1.1.2 4-Chloro-N-methoxy-N-methylbenzamide 11b According to the representative procedure above, the title compound was obtained from the corresponding carboxylic acid (20 mmol) to give colorless oil (4.0 g, 99%). Rf = 0.20 (petroleum ether/EtOAc 3:1); IR (KBr): = 3068, 2963, 2934, 1644, 1593, 1458, 1417, 1380, 1212, 1091 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.64-7.61 (m, 2H), 7.36-7.33 (m, 2H), 3.50 (s, 3H), 3.32 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ = 168.8, 136.7, 132.3, 129.9, 128.2, 61.1, 33.5 ppm; MS (E.I., 70 eV) m/z 199, 168, 141, 139 (100), 113, 111, 85, 75.
96%	Stage #1: para-chlorobenzoic acid With triethylamine; trichloromethyl chloroformate In dichloromethane at 0℃; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane at 25℃; for 1h;

94%	Stage #1: para-chlorobenzoic acid With trichloroacetonitrile; triphenylphosphine In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 20℃; for 1h; Inert atmosphere;
88%	With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 12h;	4-Chloro-iV-methoxy-iV-methylbenzamide [0116] 4-Chloro-iV-methoxy-iV-methylbenzamide: Commercially available 4-chlorobenzoic acid (3.4913g, 22.3 mmol, 1.00 equiv) was suspended in CH2CI2 (30 mL) and cooled to 0 °C at which time Me(OMe)NH FontWeight="Bold" FontSize="10" HCl (2.39 g, 24.5 mmol, 1.10 equiv), N-methymorpholine (2.48 g, 2.70 mL, 24.5 mmol, 1. 10 equiv), and N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride ( 4.70 g, 24.5 mmol, 1.10 equiv) were added sequentially. After stirring for 12 h the reaction was quenched with NH4C1 (sat. aq.) and the layers were separated. The aqueous layer was back extracted with CH2CI2 (3x). The combined organic layers were washed with H20, brine, dried over Na2S04, filtered and concentrated. The crude residue was purified via Silica gel flash chromatography (1 : 1 EtO Ac/Hex) to give 3.929 g (88%) of the title compound as a clear oil. The spectral data was identical to that reported in the literatureIV: XH NMR (500 MHz, CDCI3) δ 7.68 - 7.54 (m, 2H), 7.40 - 7.29 (m, 2H), 3.49 (s, 3H), 3.31 (s, 3H) ppm.
87%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 3h;	4.2.4. N,2-Dimethoxy-N-methylbenzamide (9a) General procedure: To a solution of 3-cyanobenzoic acid 8a (3.0 g, 19.7 mmol) in DMF was added N,O-dimethylhydroxylamine hydrochloride (2.0 g, 20.7 mmol), Et3N (2.88 mL, d = 0.73, 20.7 mmol) and EDC·HCl (4.0 g, 20.7 mmol). After the mixture was stirred for 3 h at room temperature, the solvent was removed in vacuo and the residue was dissolved in EtOAc, washed with 10% citric acid, 10% NaHCO3 and saturated NaCl, and dried over Na2SO4. Then, the solvent was removed to give a colorless oil of compound 9a (3.0 g, 79%).
85%	Stage #1: para-chlorobenzoic acid With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0℃; for 0.25h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 20℃; for 1h; chemoselective reaction;	General procedure for the synthesis of Weinreb amides General procedure: A. To a mixture of benzoic acid (50 mg, 0.41 mmol, 1 equiv), PPh3 (160 mg, 0.61 mmol, 1.5 equiv) and NBS (108.5 mg, 0.61 mmol, 1.5 equiv), CH2Cl2 (2 ml) was added and the reaction was stirred at 0 °C for 15 min. The reaction was brought to room temperature and N,O-dimethylhydroxylamine hydrochloride (59.5 mg, 0.61 mmol, 1.5 equiv) and Et3N (45.5 mg, 63 µl, 0.45 mmol, 1.1 equiv) were added and reaction was stirred for 1 h at room temperature. The reaction mixture was quenched with aqueous sodium bicarbonate solution and diluted with CH2Cl2. The bicarbonate washings were again extracted with CH2Cl2 and the combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography was performed using EtOAc/Petroleum ether (1:5).
83%	With 2-bromo-1-methyl-pyridinium iodide; triethylamine In dichloromethane for 6h; Heating;
71%	With triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃;
68%	Stage #1: para-chlorobenzoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane
63%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 22℃; for 12h; Inert atmosphere;	4-Chloro-N-methoxy-N-methylbenzamide (2d) To a solution of 4-chlorobenzoic acid (1.0 g,5.387 mmol) in DMF (10 mL) was added N,O-dimethylhydroxyamine hydrochloride (685.3mg, 7.026 mmol), EDC hydrochloride (mg, mmol) and TEA (1.64 g, 2.25 mL, 16.161 mmol).Then the reaction mixture was stirred at 22 oC for 12 h. After the reaction was completed, water was added to the reaction mixture and it was extracted with EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting crude residue was purified by flash column chromatography (n-hexane: EtOAc = 4:1)to give the desired product (676.5 mg, 3.389 mmol, 63%) as a colorless liquid. 1H NMR (400MHz, CDCl3) δ 7.64 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 3.52 (s, 3H), 3.34 (s, 3H);13C NMR (100 MHz, CDCl3) δ 168.6, 136.7, 132.3, 129.8, 128.2, 61.1, 33.5.
	In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;
	Stage #1: para-chlorobenzoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane at 20℃;

Reference： [1]Hioki, Kazuhito; Kobayashi, Hiroko; Ohkihara, Rumi; Tani, Shohei; Kunishima, Munetaka [Chemical and Pharmaceutical Bulletin, 2004, vol. 52, # 4, p. 470 - 472]
[2]Gembus, Vincent; Furman, Christophe; Millet, Régis; Mansouri, Roxane; Chavatte, Philippe; Levacher, Vincent; Brière, Jean-François [European Journal of Medicinal Chemistry, 2012, vol. 58, p. 396 - 404]
[3]Kim, Misoo; Lee, Hagyoung; Han, Ki-Jong; Kay, Kwang-Yol [Synthetic Communications, 2003, vol. 33, # 23, p. 4013 - 4018]
[4]Location in patent: experimental part Kim, Joong-Gon; Jang, Doo Ok [Bulletin of the Korean Chemical Society, 2010, vol. 31, # 1, p. 171 - 173]
[5]Current Patent Assignee: UNIVERSITY OF PENNSYLVANIA - WO2014/47257, 2014, A2 Location in patent: Paragraph 0116
[6]Location in patent: experimental part Hayashi, Yoshio; Yamazaki, Yuri; Sumikura, Makiko; Masuda, Yurika; Hayashi, Yoshiki; Yasui, Hiroyuki; Kiso, Yoshiaki; Chinen, Takumi; Usui, Takeo; Yakushiji, Fumika; Potts, Barbara; Neuteboom, Saskia; Palladino, Michael; Lloyd, George Kenneth [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4279 - 4289]
[7]Pilathottathil, Fathima; Vineet Kumar, Doppalapudi; Kaliyamoorthy, Alagiri [Synthetic Communications, 2020, vol. 50, # 11, p. 1622 - 1632]
[8]Sibi; Stessman; Schultz; Christensen; Lu; Marvin [Synthetic Communications, 1995, vol. 25, # 8, p. 1255 - 1264]
[9]Davies, Jacob; Booth, Samuel G.; Essafi, Stephanie; Dryfe, Robert A. W.; Leonori, Daniele [Angewandte Chemie - International Edition, 2015, vol. 54, # 47, p. 14017 - 14021][Angew. Chem., 2015, vol. 127, # 47, p. 14223 - 14227,5]
[10]Yang, Yang; Liu, Jian; Kamounah, Fadhil S.; Ciancaleoni, Gianluca; Lee, Ji-Woong [Journal of Organic Chemistry, 2021, vol. 86, # 23, p. 16867 - 16881]
[11]Gim, Hyo Jin; Jung, Michael E. [Synthesis, 2019, vol. 51, # 12, p. 2548 - 2552]
[12]Chen, Ying-Chun; Du, Fei; Jiang, Kun; Liang, Wu; Ouyang, Qin; Shuai, Li; Wei, Ye; Yang, Jie [Angewandte Chemie - International Edition, 2020, vol. 59, # 43, p. 19222 - 19228][Angew. Chem., 2020, vol. 132, # 43, p. 19384 - 19390,7]
[13]Denisenko, Aleksandr; Garbuz, Pavel; Mykhailiuk, Pavel K.; Shishkina, Svetlana V.; Voloshchuk, Nataliya M. [Angewandte Chemie - International Edition, 2020, vol. 59, # 46, p. 20515 - 20521][Angew. Chem., 2020, vol. 132, # 46, p. 20696 - 20702,7]

2
[ 1117-97-1 ]
[ 74-11-3 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: N,0-dimethylhydroxylamine; para-chlorobenzoic acid In toluene at 0℃; for 0.166667h; Stage #2: With phosphorus trichloride In toluene at 20 - 60℃; for 0.5h;	N-Methoxy-N-methylbenzamide (3a);^38,39Typical Procedure General procedure: A solution of NHMe(OMe) (0.360 g, 6.0 mmol) and benzoic acid (0.244 g, 2.0 mmol) was stirred in dry toluene (10 mL) at 0 °C for 10 min. A solution of PCl3 (0.137 g, 1.0 mmol) in dry toluene (2 mL) was then added dropwise to the mixture. The mixture was warmed to r.t. slowly and then stirred at 60 °C for 0.5 h. When the reaction was complete (TLC monitoring), the mixture was cooled to r.t. The mixture was then quenched with sat. NaHCO3 soln (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd MgSO4). The solvent was removed in vacuo.The product was purified by column chromatography (silica gel, petroleum ether-EtOAc, 3:2) to give pure 3a as a colorless oil; yield: 320 mg (97%).
	With 1,1'-carbonyldiimidazole
	With triethylamine; 1,1'-carbonyldiimidazole

Reference： [1]Niu, Teng; Wang, Ke-Hu; Huang, Danfeng; Xu, Changming; Su, Yingpeng; Hu, Yulai; Fu, Ying [Synthesis, 2014, vol. 46, # 3, p. 320 - 330]
[2]Branca, Quirico; Jakob-Roetne, Roland; Kettler, Rolf; Roever, Stephan; Scalone, Michelangelo [Chimia, 1995, vol. 49, # 10, p. 381 - 385]
[3]Location in patent: scheme or table Lee, Ki-Ho; Park, Chun-Eung; Min, Kyung-Hyun; Shin, Yong-Je; Chung, Coo-Min; Kim, Hui-Ho; Yoon, Hae-Jeoung; Won-Kim; Ryu, Eun-Ju; Shin, Yu-Jin; Nam, Hyun-Sik; Cho, Jeong-Woo; Lee, Hee-Yoon [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 18, p. 5567 - 5571]

3
[ 122-01-0 ]
[ 1117-97-1 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	In tetrahydrofuran at -78℃; for 3h;
	With pyridine In chloroform
	With triethylamine In dichloromethane at 0 - 20℃; for 4h;

With triethylamine

Reference： [1]Murphy, John A.; Commeureuc, Aurelien G. J.; Snaddon, Thomas N.; McGuire, Thomas M.; Khan, Tanweer A.; Hisler, Kevin; Dewis, Mark L.; Carling, Robert [Organic Letters, 2005, vol. 7, # 7, p. 1427 - 1429]
[2]Turnbull, Kenneth; Sun, Congcong; Krein, Douglas M. [Tetrahedron Letters, 1998, vol. 39, # 12, p. 1509 - 1512]
[3]Location in patent: experimental part Debnath, Joy; Siricilla, Shajila; Wan, Bajoie; Crick, Dean C.; Lenaerts, Anne J.; Franzblau, Scott G.; Kurosu, Michio [Journal of Medicinal Chemistry, 2012, vol. 55, # 8, p. 3739 - 3755]
[4]Tan, Xuefeng; Massignan, Leonardo; Hou, Xiaoyan; Frey, Johanna; Oliveira, João C. A.; Hussain, Masoom Nasiha; Ackermann, Lutz [Angewandte Chemie - International Edition, 2021, vol. 60, # 24, p. 13264 - 13270][Angew. Chem., 2020, vol. 133, p. 13373 - 13379,7]

4
[ 29786-93-4 ]
[ 122334-37-6 ]
[ 25017-08-7 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran at 0 - 20℃; for 0.2h; Yield given;

Reference： [1]Lee, Na Ra; Lee, Jae In [Synthetic Communications, 1999, vol. 29, # 8, p. 1249 - 1255]

5
[ 6638-79-5 ]
[ 122-01-0 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In dichloromethane at 0 - 20℃;
96%	Stage #1: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 0℃; Inert atmosphere; Stage #2: 4-chloro-benzoyl chloride In dichloromethane at 0 - 20℃; Inert atmosphere;
92%	With triethylamine In dichloromethane at 0 - 20℃;

92%	With triethylamine In dichloromethane at 0 - 20℃;	XVII.B Step B: Preparation of 4-Chloro-N-methoxy-N-methyl-benzamide. A 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and an addition funnel was charged with N,O-dimethylhydroxylamine hydrochloride (20 g, 0.20 mol) and CH2Cl2 (250 mL). The mixture was cooled to 0° C. and triethylamine (24 g, 0.20 mol) was added, followed by a solution of 4-chlorobenzoyl chloride (35.8 g, 0.2 mol) in CH2Cl2 (100 mL). After the addition was complete, the cooling bath was removed, and the reaction was allowed to warm to rt and was stirred overnight. The reaction mixture was quenched with satd. aq. NH4Cl (200 mL). The mixture was transferred to a separatory funnel, the layers were separated and the aqueous layer was extracted with CH2Cl2 (200 mL). The combined organic layers were washed with aq. NaHCO3, brine, and then dried over anhydrous MgSO4. After filtration, the solvents were evaporated under reduced pressure to afford the benzamide (37 g, 92%) as a colorless oil. IR (film): 2935, 1639, 1593, 1460, 1415, 1212, 1090, 1015, 887, 838, 747, 730 cm-1. 1H NMR (400 MHz, CDCl3): δ7.58 (d, J=8.6 Hz, 2H), 7.32 (d, J=8.6 Hz, 2H), 3.55 (s, 3H), 3.11 (s, 3H). 13C NMR (100 MHz, CDCl3): δ169.2, 137.3, 132.9, 130.5, 128.8, 61.7, 34.1. HRMS (EI): m/z calcd for C9H11ClNO2 [M+H]+, 200.0478; found, 200.0484
72%	With pyridine In dichloromethane at 20℃; Inert atmosphere;
	With triethylamine In dichloromethane
	With triethylamine In dichloromethane at 20℃; for 24h;
	With pyridine In dichloromethane
27.9 gm (95%)	In sodium hydroxide; dichloromethane	VII 4-chloro-N-methyl-N-methoxybenzamide PREPARATION VII 4-chloro-N-methyl-N-methoxybenzamide To a solution of 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 165(M+) IR: 3011, 2974, 2938, 1634 cm-1
27.9 gm (95%)	In sodium hydroxide; dichloromethane	VII 4-chloro-N-methyl-N-methoxybenzamide PREPARATION VII 4-chloro-N-methyl-N-methoxybenzamide To a solution of 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 165(M+) IR: 3011, 2974, 2938, 1634 cm-1
27.9 gm (95%)	In sodium hydroxide; dichloromethane	B.II 4-chloro-N-methyl-N-methoxybenzamide Preparation B-II 4-chloro-N-methyl-N-methoxybenzamide To a solution 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient temperature. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases are combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 199(M+) IR: 3011, 2974, 2938, 1634 cm-1
	With triethylamine In dichloromethane at 20℃; Cooling with ice;	1.2 Preparation 1.2 4-Chloro-N-methoxy-N-methylbenzamide (XIII) 31.2 g of N-methoxymethanamine hydrochloride and 91.2 ml of triethylamine in 500 ml of DCM is cooled in an ice bath, and then 56 g of 4-chlorobenzoyl chloride are added slowly and the mixture is left to stir at AT for 4 hours. A mixture of ice/water is added, the mixture is extracted with DCM, the organic phase is washed with a buffer solution pH=2 and dried over Na2SO4, and the solvent is evaporated off under vacuum. 60 g of the expected compound are obtained.
22.9 g	With pyridine In dichloromethane at 20℃; Inert atmosphere;
22.9 g	With pyridine In dichloromethane at 20℃; Inert atmosphere;
	With triethylamine
	With pyridine In dichloromethane at 20℃; for 72h;	1.a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane at 20℃; for 72h;	18.a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step
	With pyridine In dichloromethane at 20℃; for 72h;	8.a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification.
	With pyridine In dichloromethane at 20℃; for 72h;	1.a intermediate 1: step a -Ciiloro-A⁷-methoxy-yV-meiiyIbe5izamide intermediate 1: step a -Ciiloro-A7-methoxy-yV-meiiyIbe5izamide Pyridine (27.6 mL, 343 mmol) was added to Λ',Ο-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chloro benzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration and washed with DCM. The filtrate was washed with 1 N aqueous HC1 followed by water. The organic phase was dried (Na2S04), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane at 20℃; for 72h;	43.a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane at 20℃; for 72h;	43.a Intermediate 43: step a 4-chloro-N-methoxy-N-methylbenzamide Intermediate 43: step a 4-chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to Λ',Ο-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chl oro benzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 clays. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HC1 followed by water. The organic phase was dried (NaiSC ), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane at 20℃; for 72h;	8.a intermediate 8: step a 4-chloro-N-methoxy-N-methylbenzamide intermediate 8: step a4-chloro-N-methoxy-N-methylbenzamidePyridine (27.6 mL, 343 mmol) was added to N.O-dirneth lhydroxylamine hydrochloride (56.7 g, 172 mmol) in DCM (400 mL). 4-Chloro benzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 clays. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HC1 followed by water. The organic phase was dried (Na2S()4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification.
	With pyridine In dichloromethane at 20℃; for 72h;	22.a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane at 20℃; for 72h;	4-chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N, O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. The solid was removed by vacuum filtration and washed with DCM. The filtrate was washed with 1 N HCl aqueous solution and then with water. The organic phase was dried (Na2SO4), filtered and concentrated to give the crude title compound as a colorless liquid which was used without purification in the next step.
	With pyridine In dichloromethane
	With triethylamine In dichloromethane at 0 - 20℃; for 6h; Inert atmosphere;
	With pyridine In water	4-Chloro-N-methoxy-N-methylbenzamide Intermediate 1: Step a 4-Chloro-N-methoxy-N-methylbenzamide Pyridine (27.6 mL, 343 mmol) was added to N,O-dimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration, washing with DCM. The filtrate was washed with 1 N aqueous HCl followed by water. The organic phase was dried (Na2SO4), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.
	With triethylamine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;
27.9 gm (95%)	In sodium hydroxide; dichloromethane	B.II 4-chloro-N-methyl-N-methoxybenzamide Preparation B-II 4-chloro-N-methyl-N-methoxybenzamide To a solution 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient temperature. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases are combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 199(M+) IR: 3011, 2974, 2938, 1634 cm-1
27.9 gm (95%)	In sodium hydroxide; dichloromethane	VII 4-chloro-N-methyl-N-methoxybenzamide PREPARATION VII 4-chloro-N-methyl-N-methoxybenzamide To a solution of 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 165(M+) IR: 3011, 2974, 2938, 1634 cm-1
27.9 gm (95%)	In sodium hydroxide; dichloromethane	B.II 4-chloro-N-methyl-N-methoxybenzamide PREPARATION B-II 4-chloro-N-methyl-N-methoxybenzamide To a solution 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient temperature. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases are combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 199(M+); IR: 3011, 2974, 2938, 1634 cm-1
27.9 gm (95%)	In sodium hydroxide; dichloromethane	II 4-chloro-N-methyl-N-methoxybenzamide Preparation II 4-chloro-N-methyl-N-methoxybenzamide To a solution 11.38 gm (116.7 mMol) N-methoxy-N-methyl amine hydrochloride in 700 mL 1N sodium hydroxide was added a solution of 18.56 gm (106.04 mMol) 4-chlorobenzoyl chloride in 200 mL dichloromethane and the mixture was stirred at ambient temperature. After 18 hours the phases were separated and the remaining aqueous was extracted well with dichloromethane. All organic phases are combined, dried over sodium sulfate and concentrated under reduced pressure to give 27.9 gm (95%) of the title compound as a clear oil. MS(m/e): 199(M+) IR: 3011, 2974, 2938, 1634 cm-1
	With triethylamine In dichloromethane at 0 - 20℃; for 3h;

Reference： [1]Keenan, Martine; Abbott, Michael J.; Alexander, Paul W.; Armstrong, Tanya; Best, Wayne M.; Berven, Bradley; Botero, Adriana; Chaplin, Jason H.; Charman, Susan A.; Chatelain, Eric; Von Geldern, Thomas W.; Kerfoot, Maria; Khong, Andrea; Nguyen, Tien; McManus, Joshua D.; Morizzi, Julia; Ryan, Eileen; Scandale, Ivan; Thompson, R. Andrew; Wang, Sen Z.; White, Karen L. [Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4189 - 4204]
[2]Kishore Kumar; Chavarria, Gustavo E.; Charlton-Sevcik, Amanda K.; Arispe, Wara M.; MacDonough, Matthew T.; Strecker, Tracy E.; Chen, Shen-En; Siim, Bronwyn G.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 4, p. 1415 - 1419]
[3]Mani, Neelakandha S.; Jablonowski, Jill A.; Jones, Todd K. [Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8115 - 8117]
[4]Current Patent Assignee: JOHNSON & JOHNSON INC - US2005/250948, 2005, A1 Location in patent: Page/Page column 41
[5]Phetcharawetch, Jongkonporn; Betterley, Nolan M.; Soorukram, Darunee; Pohmakotr, Manat; Reutrakul, Vichai; Kuhakarn, Chutima [European Journal of Organic Chemistry, 2017, vol. 2017, # 46, p. 6840 - 6850]
[6]Piotrowski, David W. [Synlett, 1999, # 7, p. 1091 - 1093]
[7]Li, Xiaolin; Hewgley, J. Brian; Mulrooney, Carol A.; Yang, Jaemoon; Kozlowski, Marisa C. [Journal of Organic Chemistry, 2003, vol. 68, # 14, p. 5500 - 5511]
[8]Bhatt, Ulhas; Duffy, Bryan C.; Guzzo, Peter R.; Cheng, Leifeng; Elebring, Thomas [Synthetic Communications, 2007, vol. 37, # 16, p. 2793 - 2806]
[9]Current Patent Assignee: ELI LILLY & CO - US5708008, 1998, A
[10]Current Patent Assignee: ELI LILLY & CO - EP824917, 1998, A2
[11]Current Patent Assignee: ELI LILLY & CO - EP824917, 1998, A2
[12]Current Patent Assignee: SANOFI - US2009/281107, 2009, A1 Location in patent: Page/Page column 9
[13]Chennamaneni, Naveen Kumar; Arif, Jenifer; Buckner, Frederick S.; Gelb, Michael H. [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 23, p. 6582 - 6584]
[14]Location in patent: experimental part Kraus, James M.; Verlinde, Christophe L. M. J.; Karimi, Mandana; Lepesheva, Galina I.; Gelb, Michael H.; Buckner, Frederick S. [Journal of Medicinal Chemistry, 2009, vol. 52, # 6, p. 1639 - 1647] Location in patent: experimental part Kraus, James M.; Tatipaka, Hari Babu; McGuffin, Sarah A.; Chennamaneni, Naveen Kumar; Karimi, Mandana; Arif, Jenifer; Verlinde, Christophe L. M. J.; Buckner, Frederick S.; Gelb, Michael H. [Journal of Medicinal Chemistry, 2010, vol. 53, # 10, p. 3887 - 3898]
[15]Li, Wanfang; Fan, Weizheng; Ma, Xin; Tao, Xiaoming; Li, Xiaoming; Xie, Xiaomin; Zhang, Zhaoguo [Chemical Communications, 2012, vol. 48, # 71, p. 8976 - 8978]
[16]Current Patent Assignee: JOHNSON & JOHNSON INC - US2014/107094, 2014, A1 Location in patent: Paragraph 0375; 0376
[17]Current Patent Assignee: JOHNSON & JOHNSON INC - US2014/107097, 2014, A1 Location in patent: Paragraph 0310; 0311
[18]Current Patent Assignee: JOHNSON & JOHNSON INC - US2015/105404, 2015, A1 Location in patent: Paragraph 0225
[19]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2015/57200, 2015, A1 Location in patent: Page/Page column 38
[20]Current Patent Assignee: JOHNSON & JOHNSON INC - US2015/105366, 2015, A1 Location in patent: Paragraph 0403; 0404
[21]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2015/57205, 2015, A1 Location in patent: Page/Page column 113
[22]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2015/57203, 2015, A1 Location in patent: Page/Page column 58
[23]Current Patent Assignee: JOHNSON & JOHNSON INC - US2015/111870, 2015, A1 Location in patent: Paragraph 0411; 0412
[24]Current Patent Assignee: JOHNSON & JOHNSON INC - KR2016/70823, 2016, A Location in patent: Paragraph 0161-00164
[25]Kummer, David A.; Cummings, Maxwell D.; Abad, Marta; Barbay, Joseph; Castro, Glenda; Wolin, Ronald; Kreutter, Kevin D.; Maharoof, Umar; Milligan, Cynthia; Nishimura, Rachel; Pierce, Joan; Schalk-Hihi, Celine; Spurlino, John; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Woods, Craig; Xue, Xiaohua; Edwards, James P.; Fourie, Anne M.; Leonard, Kristi [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 2047 - 2057]
[26]Das, Riki; Kapur, Manmohan [Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126]
[27]Current Patent Assignee: JOHNSON & JOHNSON INC - US2014/107096, 2014, A1 Location in patent: Page/Page column
[28]Huang, Fei; Zhang, Songlin [Organic Letters, 2019, vol. 21, # 18, p. 7430 - 7434]
[29]Current Patent Assignee: ELI LILLY & CO - EP832650, 1998, A2
[30]Current Patent Assignee: ELI LILLY & CO - EP832650, 1998, A2
[31]Current Patent Assignee: ELI LILLY & CO - US5962473, 1999, A
[32]Current Patent Assignee: ELI LILLY & CO - US5708187, 1998, A
[33]Yin, Qi; Wen, Xiaolu; Chen, Yiwei; Gong, Xiangnan; Hu, Lin [Organic Letters, 2021, vol. 23, # 19, p. 7529 - 7534]

6
[ 110-89-4 ]
[ 13291-18-4 ]
[ 122334-37-6 ]
3-piperidino-2-methyl-1-[3-(6-chloropyridyl)]-1-propanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: isopropenylmagnesium bromide; 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at 0 - 20℃; for 1.16667h; Stage #2: piperidine In tetrahydrofuran; water at 20℃; for 0.333333h; Further stages.;

Reference： [1]Gomtsyan; Koenig; Lee [Journal of Organic Chemistry, 2001, vol. 66, # 10, p. 3613 - 3616]

7
[ 122334-37-6 ]
[ 117423-41-3 ]
2-(<i>tert</i>-butyl-dimethyl-silanyloxy)-1-(4-chloro-phenyl)-2-pyridin-4-yl-ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-((tert-butyldimethylsilyloxy)methyl)pyridine With lithium diisopropyl amide In tetrahydrofuran at -30℃; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -30 - 0℃;

Reference： [1]Chang, Linda L.; Sidler, Kelly L.; Cascieri, Margaret A.; De Laszlo, Stephen; Koch, Greg; Li, Bing; MacCoss, Malcolm; Mantlo, Nathan; O'Keefe, Stephen; Pang, Margaret; Rolando, Anna; Hagmann, William K. [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 18, p. 2549 - 2553]

8
[ 110-89-4 ]
[ 661-54-1 ]
[ 122334-37-6 ]
(Z)-1-(4-Chloro-phenyl)-4,4,4-trifluoro-3-piperidin-1-yl-but-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 3,3,3-trifluoroprop-1-yne With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -78 - 0℃; Stage #3: piperidine With water In tetrahydrofuran at 0℃;

Reference： [1]Jeong, In Howa; Jeon, Sung Lan; Min, Yong Ki; Kim, Bum Tae [Tetrahedron Letters, 2002, vol. 43, # 40, p. 7171 - 7174]

9
[ 93-04-9 ]
[ 122334-37-6 ]
4-chlorophenyl 3-methoxynaphth-2-yl ketone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-Methoxynaphthalene With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at 20℃; for 3h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at 20℃;

Reference： [1]Li, Xiaolin; Hewgley, J. Brian; Mulrooney, Carol A.; Yang, Jaemoon; Kozlowski, Marisa C. [Journal of Organic Chemistry, 2003, vol. 68, # 14, p. 5500 - 5511]

10
[ 122334-37-6 ]
[ 190898-86-3 ]
[ 406162-21-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline With n-butyllithium In tetrahydrofuran at -70℃; for 0.5h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -70℃; for 0.5h; Further stages.;

Reference： [1]Angibaud, Patrick R.; Venet, Marc G.; Filliers, Walter; Broeckx, Rudy; Ligny, Yannick A.; Muller, Philippe; Poncelet, Virginie S.; End, Dave W. [European Journal of Organic Chemistry, 2004, # 3, p. 479 - 486]

11
[ 122334-37-6 ]
[ 253453-91-7 ]
[ 807614-69-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	With n-butyllithium; In tetrahydrofuran; hexane; at -78 - 20℃;	Step C: (2-Chloro-3-methyl-3H-imidazol-4-yl)-(4-chloro-phenyl)-methanone. To a 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and an addition funnel was added <strong>[253453-91-7]<strong>[253453-91-7]2-chloro-1-methyl-1H-imidazol</strong>e</strong> (15 g, 0.128 mol) and THF (250 mL). The reaction mixture was cooled to -78 C. and n-BuLi (2.5 M in hexanes, 54 mL, 0.135 mol) was added. The pale yellow suspension that formed was stirred for 1 h and a solution of 4-chloro-N-methoxy-N-methyl-benzamide (27 g, 0.135 mol) in THF (50 mL) was then added dropwise. After the addition was complete, the cooling bath was removed and the reaction was allowed to warm to rt. The reaction mixture was quenched with satd. aq. NH4Cl (150 mL), transferred to a separatory funnel, and extracted with EtOAc (1.5 L). The organic layer was washed with water, brine and dried over anhydrous Na2SO4. After filtration, the solvents were evaporated under reduced pressure to yield the product as a crystalline solid. Recrystallization from EtOAc-hexanes afforded the desired ketone (31.2 g, 97%) as a white crystalline solid. mp 173-174 C. IR (film): 1639, 1589, 1517, 1395, 1377, 1253, 1186, 902, 841, 756, 738, 695, 676 cm-1. 1H NMR (400 MHz, CDCl3): delta7.78 (d, J=8.6 Hz, 2H), 7.44 (s, 1H), 7.44 (d, J=8.6 Hz, 2H), 3.97 (s, 3H). 13C NMR (100 MHz, CDCl3): delta183.3, 140.3, 139.5, 139.2, 136.3, 131.2, 130.4, 128.9, 33.5. HRMS (EI): m/z calcd for C11H9Cl2N2O [M+H]+, 255.0092; found, 255.0104. Anal. Calcd for C11H8Cl2N2O: C, 51.8; H, 3.06; N, 10.93. Found: C, 52.08; H, 3.16; N, 10.90.

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 8115 - 8117
[2]Patent: US2005/250948,2005,A1 .Location in patent: Page/Page column 41

12
[ 52415-29-9 ]
[ 122334-37-6 ]
[ 81223-74-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: 6-bromo-1H-indole With tert.-butyl lithium; potassium hydride In diethyl ether at -78℃; for 0.166667h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In diethyl ether at -78 - 20℃; for 1h;

Reference： [1]Li, Qun; Li, Tongmei; Woods, Keith W.; Gu, Wen-Zhen; Cohen, Jerry; Stoll, Vincent S.; Galicia, Tomas; Hutchins, Charles; Frost, David; Rosenberg, Saul H.; Sham, Hing L. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 11, p. 2918 - 2922]

13
[ 1779-51-7 ]
[ 122334-37-6 ]
[ 25017-08-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: n-butyl(triphenyl)phosphonium bromide With n-butyllithium In tetrahydrofuran; hexane at -15℃; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; diethyl ether; hexane at 20℃;

Reference： [1]Murphy, John A.; Commeureuc, Aurelien G. J.; Snaddon, Thomas N.; McGuire, Thomas M.; Khan, Tanweer A.; Hisler, Kevin; Dewis, Mark L.; Carling, Robert [Organic Letters, 2005, vol. 7, # 7, p. 1427 - 1429]

14
[ 21406-61-1 ]
[ 122334-37-6 ]
[ 7295-50-3 ]

Reference： [1]Organic Letters,2005,vol. 7,p. 1427 - 1429

15
[ 1779-49-3 ]
[ 122334-37-6 ]
[ 99-91-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: Methyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran; hexane at -15℃; for 0.666667h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 20℃; for 20h; Stage #3: With hydrogenchloride In tetrahydrofuran; diethyl ether; hexane at 20℃;

Reference： [1]Murphy, John A.; Commeureuc, Aurelien G. J.; Snaddon, Thomas N.; McGuire, Thomas M.; Khan, Tanweer A.; Hisler, Kevin; Dewis, Mark L.; Carling, Robert [Organic Letters, 2005, vol. 7, # 7, p. 1427 - 1429]

16
[ 7484-37-9 ]
[ 122334-37-6 ]
[ 126314-18-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: (3-phenylpropyl)triphenylphosphonium bromide With n-butyllithium In tetrahydrofuran; hexane at -15℃; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; diethyl ether; hexane at 20℃;

Reference： [1]Murphy, John A.; Commeureuc, Aurelien G. J.; Snaddon, Thomas N.; McGuire, Thomas M.; Khan, Tanweer A.; Hisler, Kevin; Dewis, Mark L.; Carling, Robert [Organic Letters, 2005, vol. 7, # 7, p. 1427 - 1429]

17
[ 106-39-8 ]
[ 201230-82-2 ]
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 105℃; for 12h; Inert atmosphere; Green chemistry;
87%	With sodium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 80℃; for 19h;
87%	With palladium diacetate; sodium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 80℃; for 19h;

Reference： [1]Thanh Dang, Tuan; Chen, Anqi; Majeed Seayad, Abdul [RSC Advances, 2014, vol. 4, # 57, p. 30019 - 30027]
[2]Martinelli, Joseph R.; Freckmann, Dominique M. M.; Buchwald, Stephen L. [Organic Letters, 2006, vol. 8, # 21, p. 4843 - 4846]
[3]Martinelli, Joseph R.; Watson, Donald A.; Freckmann, Dominique M. M.; Barder, Timothy E.; Buchwald, Stephen L. [Journal of Organic Chemistry, 2008, vol. 73, # 18, p. 7102 - 7107]

18
[ 122334-37-6 ]
[ 129752-86-9 ]
[ 654682-18-5 ]

Yield	Reaction Conditions	Operation in experiment
59%	In diethyl ether

Reference： [1]Bhatt, Ulhas; Duffy, Bryan C.; Guzzo, Peter R.; Cheng, Leifeng; Elebring, Thomas [Synthetic Communications, 2007, vol. 37, # 16, p. 2793 - 2806]

19
[ 540-88-5 ]
[ 122334-37-6 ]
[ 106970-98-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: acetic acid tert-butyl ester With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -78 - 20℃; for 4h; Further stages.;
421 mg	Stage #1: acetic acid tert-butyl ester With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78℃; for 1h;

Reference： [1]Bhatt, Ulhas; Duffy, Bryan C.; Guzzo, Peter R.; Cheng, Leifeng; Elebring, Thomas [Synthetic Communications, 2007, vol. 37, # 16, p. 2793 - 2806]
[2]Yin, Qi; Wen, Xiaolu; Chen, Yiwei; Gong, Xiangnan; Hu, Lin [Organic Letters, 2021, vol. 23, # 19, p. 7529 - 7534]

20
[ 661-54-1 ]
[ 122334-37-6 ]
C₁₀H₄Cl₃F₃O [ No CAS ]
C₁₂H₁₀F₃Cl₂NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 63% 2: 15%	Stage #1: 3,3,3-trifluoroprop-1-yne With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -78 - 0℃; Stage #3: With trifluoromethane sulfonyl chloride In tetrahydrofuran Further stages.;

Reference： [1]Jeon, Sung Lan; Kim, Joa Kyum; Son, Jang Bae; Kim, Bum Tae; Jeong, In Howa [Journal of Fluorine Chemistry, 2007, vol. 128, # 2, p. 153 - 157]

21
[ 122334-37-6 ]
[ 465615-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 1.2: 97 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: 78 percent / NaH / tetrahydrofuran / 36 h / 60 °C

Reference： [1]Mani, Neelakandha S.; Jablonowski, Jill A.; Jones, Todd K. [Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8115 - 8117]

22
[ 122334-37-6 ]
[ 64634-96-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-BuLi; TMEDA / tetrahydrofuran; hexane / 3 h / 20 °C 1.2: tetrahydrofuran; hexane / 20 °C 2.1: n-Bu₄NI; BCl₃ / CH₂Cl₂; hexane / 1.17 h / -78 - 20 °C

Reference： [1]Li, Xiaolin; Hewgley, J. Brian; Mulrooney, Carol A.; Yang, Jaemoon; Kozlowski, Marisa C. [Journal of Organic Chemistry, 2003, vol. 68, # 14, p. 5500 - 5511]

23
[ 122334-37-6 ]
[3'-(4-chloro-benzoyl)-2,2'-dihydroxy-1,1'-binaphthalenyl-3-yl]-(4-chloro-phenyl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: n-BuLi; TMEDA / tetrahydrofuran; hexane / 3 h / 20 °C 1.2: tetrahydrofuran; hexane / 20 °C 2.1: n-Bu₄NI; BCl₃ / CH₂Cl₂; hexane / 1.17 h / -78 - 20 °C 3.1: (S,S)-1,5-diaza-cis-decalin; CuI; O₂ / CH₂Cl₂; acetonitrile / 24 h / 40 °C / 760 Torr

Reference： [1]Li, Xiaolin; Hewgley, J. Brian; Mulrooney, Carol A.; Yang, Jaemoon; Kozlowski, Marisa C. [Journal of Organic Chemistry, 2003, vol. 68, # 14, p. 5500 - 5511]

24
C₈H₅LiN^(1-)*K⁽¹⁺⁾ [ No CAS ]
[ 122334-37-6 ]
[ 405275-23-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₈H₅LiN^(1-)*K⁽¹⁺⁾; 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -78 - 20℃; Stage #2: With phosphoric acid; water at 0℃;	16.1a Example 16 5-(4-Chlorobenzoyl)-1-ethyl-1H-indole [0388] 1a) 5-(4-Chlorobenzoyl)-1H-indole In a three-necked flask fitted with a coolant, a calcium chloride trap, a dropping funnel and under nitrogen, place 1.82 g (9.1 mmol) of potassium hydride in 20 mL of anhydrous tetrahydrofuran. Cool to 0° C. then add drop by drop 5-bromo-1H-indole diluted in 5 mL of tetrahydrofuran. After 15 minutes, the mixture is cooled to -78° C. and 12.2 mL (18.2 ml) of tert-butyllithium previously cooled to -78° C. are added using a dropper. After 15 minutes, 3.63 g (18.2 mmol) of N-methoxy-N-methyl-4-chlorobenzamide diluted in 5 mL of anhydrous tetrahydrofuran are added drop by drop. Allow to return slowly to ambient temperature then pour the solution slowly into 100 mL of 1M phosphoric acid previously cooled in ice; extract with diethyl ether, wash with an aqueous 5% solution of sodium bicarbonate, dry over anhydrous sodium sulfate and evaporate. Purify the evaporation residue by chromatography on silica gel with elution by diisopropyl ether (Int. 53). [0389] Yield: 28% [0390] Melting point: 130-132° C. (diisopropyl ether)

Reference： [1]Current Patent Assignee: YANG JI CHEMICAL - US2004/67998, 2004, A1 Location in patent: Page/Page column 18-19

25
[ 95-73-8 ]
ammonium chloride [ No CAS ]
[ 122334-37-6 ]
3-(4-chlorobenzoyl)-2,4-dichlorotoluene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran	1.c (Following Scheme A) (c) Synthesis of 3-(4-chlorobenzoyl)-2,4-dichlorotoluene (Following Scheme A) n-BuLi (1.6M, 76 ml) was added dropwise to a solution of 2,4-dichlorotoluene (16.7 ml, 121 mmol) in dry THF (125 ml) at -78° C. under a nitrogen atmosphere. After 1 h a solution of N-methoxy-N-methyl-4-chlorobenzamide (24.26 g, 1 eq.) in dry THF (50 ml) was added slowly to the reaction mixture and the stirring was continued for an additional 1 h. The reaction was then quenched with 1M NH4 Cl, and allowed to room temperature. The solvent was removed in vacuo and the resulting mixture was diluted with ether. The organic layer was separated, washed with 1M NH4 Cl, water, and brine, and dried over MgSO4. The solvent was removed in vacuo to give an oil, which upon crystallization from hexanes gave 3-(4-chlorobenzoyl)-2,4-dichlorotoluene (19.98 g) as white crystals, mp 132.0°-135.8° C.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US5886178, 1999, A

26
H₂ SO₄ [ No CAS ]
[ 141-97-9 ]
[ 122334-37-6 ]
[ 4111-54-0 ]
[ 43053-63-0 ]

Yield	Reaction Conditions	Operation in experiment
	With NaH In tetrahydrofuran	O 6-(4-Chlorophenyl)-4-hydroxy-2H-pyran-2-one Example O 6-(4-Chlorophenyl)-4-hydroxy-2H-pyran-2-one The title compound (1.56 g, m.p. 247-249° C.) was prepared in a similar manner as that demonstrated in the preparation of Example N using the following: 60% NaH (0.904 g, 22.6 mmol), THF (50 mL), ethyl acetoacetate (3.00 g, 22.6 mmol), lithium diisopropylamine in THF (39.8 mL, 24 mmol), 4-chloro-N-methoxy-N-methylbenzamide (3.73 g, 22.6 mmol), 90% H2 SO4 (20 mL). H NMR (300 MHz, DMSO-d6) δ11.950 (bs, 1 H), 7.878 (d, 1 H, J=9 Hz), 7.584 (d, 1 H, J=9 Hz), 6.812 (d, 1 H, J=2 Hz), 5.409 (d, 1 H, J=2 Hz).

Reference： [1]Current Patent Assignee: PFIZER INC - US6005103, 1999, A

27
[ 122334-37-6 ]
[ 121206-76-6 ]
5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; tert.-butyl lithium In tetrahydrofuran	20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole EXAMPLE 20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole To a suspension of 0.21 gm (1.05 mMol) potassium hydride in 5.0 mL tetrahydrofuran at 0° C. were added a solution of 0.3 gm (1.0 mMol) 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole in 5.0 mL tetrahydrofuran and the solution stirred for about 30 minutes. The resulting mixture was cooled to about -78° C. and to it were added 1.47 mL (2.3 mMol) t-butyllithium, which had been precooled to -78° C., via cannula. After about 15 minutes, a solution of 1.0 gm (5.0 mMol) N-methyl-N-methoxy-4-chlorobenzamide (Preparation VII) in 3.0 mL tetrahydrofuran were added. The reaction mixture was allowed to gradually warm to ambient and was then quenched with 2N sodium hydroxide. The mixture extracted well with diethyl ether and the ether extracts were then washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by radial chromatography (2 mm silica), eluding with 95:5 ethyl acetate:methanol, to give the title compound as a light yellow solid. m.p.=133° C. MS(m/e): 352(M+) Calculated for C21 H21 N2 OCl.0.5H2 O: Theory: C, 69.70; H, 6.13; N, 7.74. Found: C, 70.02; H, 6.20; N, 7.93.
	With sodium hydroxide; tert.-butyl lithium In tetrahydrofuran	20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole EXAMPLE 20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole To a suspension of 0.21 gm (1.05 mMol) potassium hydride in 5.0 mL tetrahydrofuran at 0°C were added a solution of 0.3 gm (1.0 mMol) 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole in 5.0 mL tetrahydrofuran and the solution stirred for about 30 minutes. The resulting mixture was cooled to about -78°C and to it were added 1.47 mL (2.3 mMol) t-butyllithium, which had been precooled to -78°C, via cannula. After about 15 minutes, a solution of 1.0 gm (5.0 mMol) N-methyl-N-methoxy-4-chlorobenzamide (Preparation VII) in 3.0 mL tetrahydrofuran were added. The reaction mixture was allowed to gradually warm to ambient and was then quenched with 2N sodium hydroxide. The mixture extracted well with diethyl ether and the ether extracts were then washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by radial chromatography (2 mm silica), eluding with 95:5 ethyl acetate:methanol, to give the title compound as a light yellow solid. m.p.=133°C MS(m/e): 352(M+) Calculated for C21H21N2OCl·0.5H2O: Theory: C, 69.70; H, 6.13; N, 7.74. Found: C, 70.02; H, 6.20; N, 7.93.
	With sodium hydroxide; tert.-butyl lithium In tetrahydrofuran	20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole EXAMPLE 20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole To a suspension of 0.21 gm (1.05 mMol) potassium hydride in 5.0 mL tetrahydrofuran at 0°C were added a solution of 0.3 gm (1.0 mMol) 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole in 5.0 mL tetrahydrofuran and the solution stirred for about 30 minutes. The resulting mixture was cooled to about -78°C and to it were added 1.47 mL (2.3 mMol) t-butyllithium, which had been precooled to -78°C, via cannula. After about 15 minutes, a solution of 1.0 gm (5.0 mMol) N-methyl-N-methoxy-4-chlorobenzamide (Preparation VII) in 3.0 mL tetrahydrofuran were added. The reaction mixture was allowed to gradually warm to ambient and was then quenched with 2N sodium hydroxide. The mixture extracted well with diethyl ether and the ether extracts were then washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by radial chromatography (2 mm silica), eluding with 95:5 ethyl acetate:methanol, to give the title compound as a light yellow solid. m.p.=133°C MS(m/e): 352(M+) Calculated for C21H21N2OCl·0.5H2O: Theory: C, 69.70; H, 6.13; N, 7.74. Found: C, 70.02; H, 6.20; N, 7.93.

With sodium hydroxide; tert.-butyl lithium In tetrahydrofuran

20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole EXAMPLE 20 5-(4-chlorobenzoyl)-3-(1-methylpiperidin-4-yl)-1H-indole To a suspension of 0.21 gm (1.05 mMol) potassium hydride in 5.0 mL tetrahydrofuran at 0° C. were added a solution of 0.3 gm (1.0 mMol) 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole in 5.0 mL tetrahydrofuran and the solution stirred for about 30 minutes. The resulting mixture was cooled to about -78° C. and to it were added 1.47 mL (2.3 mMol) t-butyllithium, which had been precooled to -78° C., via cannula. After about 15 minutes, a solution of 1.0 gm (5.0 mMol) N-methyl-N-methoxy-4-chlorobenzamide (Preparation VII) in 3.0 mL tetrahydrofuran were added. The reaction mixture was allowed to gradually warm to ambient and was then quenched with 2N sodium hydroxide. The mixture extracted well with diethyl ether and the ether extracts were then washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by radial chromatography (2 mm silica), eluding with 95:5 ethyl acetate:methanol, to give the title compound as a light yellow solid. m.p.=133° C. MS(m/e): 352(M+); Calculated for C21 H21 N2 OCl.0.5H2 O: Theory: C, 69.70; H, 6.13; N, 7.74. Found: C, 70.02; H, 6.20; N, 7.93.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US5708008, 1998, A
[2]Current Patent Assignee: ELI LILLY & CO - EP824917, 1998, A2
[3]Current Patent Assignee: ELI LILLY & CO - EP832650, 1998, A2
[4]Current Patent Assignee: ELI LILLY & CO - US5962473, 1999, A

28
[ 95-73-8 ]
[ 122334-37-6 ]
3-(4-chlorobenzoyl)-2,4-dichlorotoluene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; ammonium chloride In tetrahydrofuran	1.c (c) (c) Synthesis of 3-(4-chlorobenzoyl)-2,4-dichlorotoluene n-BuLi (1.6 M , 76 ml) was added dropwise to a solution of 2,4-dichlorotoluene (16.7 ml, 121 mmol) in dry THF (125 ml) at -78°C under a nitrogen atmosphere. After 1 h a solution of N-methoxy-N-methyl-4-chlorobenzamide (24.26 g, 1 eq.) in dry THF (50 ml) was added slowly to the reaction mixture and the stirring was continued for an additional 1 h. The reaction was then quenched with 1 M NH4Cl, and allowed to room temperature. The solvent was removed in vacuoand the resulting mixture was diluted with ether. The organic layer was separated, washed with 1 M NH4Cl, water, and brine, and dried over MgSO4. The solvent was removed in vacuoto give an oil, which upon crystallization from hexanes gave 3-(4-chlorobenzoyl)-2,4-dichlorotoluene (19.98 g) as white crystals, mp 132.0-135.8°C.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - EP810218, 1997, A1

29
[ 122334-37-6 ]
[ 26954-25-6 ]
[ 58158-45-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide; (4-pyridylmethyl)lithium In tetrahydrofuran; hexanes at -78 - 20℃; Stage #2: With water; ammonium chloride In tetrahydrofuran; hexanes	111.1 To a -78° C. solution of 4-methylpyridine (2.05 g, 22.0 mmol) in THF (50 ml) was added dropwise 2.5M BuLi solution in hexanes (9 ml, 22.5 mmol). The mixture was stirred at -78° C. for 30 min, then a solution of Weinreb amide 78 (4.00 g, 20.0 mmol) in THF (10 ml) was introduced. The mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was quenched with aqueous NH4Cl and extracted with ether. The organic phase was separated, dried over MgSO4 and concentrated to a syrup, which crystallized upon standing. Crude material was recrystallized from isopropyl ether-hexanes to yield 2.5 g of ketone 79 as a yellow solid.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2007/10513, 2007, A1 Location in patent: Page/Page column 42

30
[ 122334-37-6 ]
3-(4-chloro-benzoyl)-1-(6-methyl-pyridin-2-ylmethyl)-1H-quinolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-iodo-1-(6-methyl-pyridin-2-ylmethyl)-1H-quinolin-4-one With isopropylmagnesium chloride In tetrahydrofuran for 2h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at 20℃; for 2h; Stage #3: In tetrahydrofuran	208.3 A -78 0C solution of 3-iodo-l -(6-methyl-pyridin-2-ylmethyl)-l H-quinolin-4-one (113 mg, 0.3 mmol, 1 equiv) in 3 mL of THF was treated with 1.65 mL of isopropyl magnesium chloride (1.1 equiv) for 2 hours. Then 4-chloro-N-methoxy-N-methyl- benzamide (46 μL, 1.2 equiv) was added and stirring continued at rt for 2 hours. The reaction was quenched by slow addition of saturated aqueous solution OfNH4Cl. Standard workup followed by HPLC purification gave 3-(4-chloro-benzoyl)-l-(6-methyl-pyridin-2-ylmethyl)- 1 H-quinolin-4-one. LCMS (ES) M+H 389.1

Reference： [1]Current Patent Assignee: CHEMOCENTRYX INC - WO2007/59108, 2007, A2 Location in patent: Page/Page column 171

31
[ 439906-90-8 ]
[ 122334-37-6 ]
[ 439906-91-9 ]

Yield	Reaction Conditions	Operation in experiment
8.05 g (42%)	With n-butyllithium In tetrahydrofuran; hexane	A.6.b Example A6 b) BuLi 1.6M in hexane (0.127 mol) was added dropwise at -70° C. to a mixture of intermediate 36 (0.0577 mol) in THF (150 ml). The mixture was stirred for 1 hour. A solution of 4-chloro-N-methoxy-N-methyl-benzamide (0.0634 mol) in THF (30 ml) was added dropwise. The mixture was brought to room temperature, stirred at room temperature for 3 hours, hydrolyzed and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue was crystallized from 2-propanone and diethyl ether. The precipitate was filtered off, washed with DIPE and dried, yielding 8.05 g (42%) of 5-(4-chlorobenzoyl)-1,3-dihydro-3,3-dimethoxy-2H-indol-2-one, melting point 170° C. (intermediate 37).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2004/63944, 2004, A1

32
[ 122334-37-6 ]
[ 6873-44-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium metal trapped in the nanoscale pores of silica gel; In tetrahydrofuran; at 20℃; for 2h;Glovebox; Sealed tube; Inert atmosphere;	General procedure: In a helium-filled glove box, the desired number ofequivalents of Na-AG or Na-SG were added to a round bottom flask, along with aglass-coated stir bar, and the flask sealed with a septum. This closed systemwas then taken out of the glove box, continuously purged with nitrogen, followedby injection of the pure synthesized Weinreb amide dissolved in THF. The resulting mixture was stirred for thetime specified. After completion of the reaction, the mixture was then partitioned using ethyl acetate and brine. The organic layer was concentrated under reducedpressure using a rotary evaporator. 1H NMR of the crude product wastaken to check for reaction extent/completion and to identify the productsobtained. Crude product was fractionated and purified by columnchromatography on silica gel to afford the desired product and byproducts.

Reference： [1]Synlett,2008,p. 2132 - 2136
[2]Tetrahedron Letters,2015,vol. 56,p. 6227 - 6230

33
[ 122334-37-6 ]
[ 4949-44-4 ]
[ 1029436-75-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl propanoylacetate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; Inert atmosphere; Stage #2: With lithium diisopropyl amide In tetrahydrofuran; cyclohexane; mineral oil at 0℃; Inert atmosphere; Stage #3: 4-chloro-N-methoxy-N-methylbenzamide With hydrogenchloride In tetrahydrofuran; cyclohexane; water; mineral oil at 0 - 20℃; Inert atmosphere; Cooling with ice;	2.2 Preparation 2.2 6-(4-Chlorophenyl)-4-hydroxy-5-methyl-2H-pyran-2-one (IX) A suspension of 4.7 g of sodium hydride at 60% in oil, in 100 ml of THF, is cooled to 0° C. under a nitrogen atmosphere, a solution of 17 g of ethyl 3-oxopentanoate in 100 ml of THF is then added slowly, and the mixture is left to stir at 0° C. for 5 minutes. 86.5 ml of a 1.5 M solution of lithium diisopropylamide mono(tetrahydrofuran) in cyclohexane is then added dropwise at 0° C., and the mixture is left to stir at 0° C. for 20 minutes. Finally, a solution of 23.5 g of the compound of Preparation 1.2 in 50 ml of THF is added slowly and the mixture is left to stir while allowing the temperature to return to AT, and stirred overnight at AT. A mixture of ice/HCl at 10% is added, the reaction mixture is extracted with EtOAc, the organic phase is dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is taken up with 150 ml of concentrated H2SO4 and the mixture is left to stir at AT for 3 hours. The reaction mixture is poured onto ice and left to stir, and the precipitate formed is spin-filter-dried and washed with iso ether and then with pentane. 25 g of the expected compound are obtained after drying.

Reference： [1]Current Patent Assignee: SANOFI - US2009/281107, 2009, A1 Location in patent: Page/Page column 9

34
[ 1062512-43-9 ]
[ 74-11-3 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	In toluene at 60℃;

Reference： [1]Location in patent: scheme or table Niu, Teng; Zhang, Weiming; Huang, Danfeng; Xu, Changming; Wang, Haifeng; Hu, Yulai [Organic Letters, 2009, vol. 11, # 19, p. 4474 - 4477]

35
[ 122334-37-6 ]
[ 371764-99-7 ]
C₁₇H₂₃ClN₂OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methyl-2-triethylsilanyl-1H-imidazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.75h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Kraus, James M.; Verlinde, Christophe L. M. J.; Karimi, Mandana; Lepesheva, Galina I.; Gelb, Michael H.; Buckner, Frederick S. [Journal of Medicinal Chemistry, 2009, vol. 52, # 6, p. 1639 - 1647]

36
[ 17869-77-1 ]
[ 122334-37-6 ]
[ 1202376-68-8 ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: 3-methyl-3-(trimethylsiloxy)-1-butyne With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.666667h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78℃; for 1h;	To a -780C stirred solution of trimethyl (2-methylbut-3-yn-2-yloxy) silane (1 1.79 g, 75.15 mmol) in dry THF (100 mL), H-BuLi (14.08 mL, 22.54 mmol, 1.6 M in hexane) was added dropwise over 10 minutes under an inert atmosphere. After being stirred for 30 min at -78 0C, a solution of 4-chloro-N-methoxy-N-methylbenzamide (5.0 g, 25.0 mmol) in dry THF ( 10 mL) was added to reaction mixture and stirring was continued for an additional 1 h at -78 0C. The reaction mixture was quenched with a saturated NH4Cl solution and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 5-7 % EtOAc in hexanes to afford l-(4- chlorophenyl)-4-methyl-4-(trimethylsilyloxy) pent-2-yn-l-one (3.8 g, 57 %) as a light green oil.

Reference： [1]Current Patent Assignee: FORUM PHARMACEUTICALS INC - WO2009/158393, 2009, A1 Location in patent: Page/Page column 94

37
[ 1679-18-1 ]
[ 30289-28-2 ]
[ 122334-37-6 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 1251 - 1258

38
[ 30289-28-2 ]
potassium (4-chlorophenyl)trifluoroborate [ No CAS ]
[ 122334-37-6 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 1251 - 1258

39
[ 1826-67-1 ]
[ 122334-37-6 ]
[ 100-46-9 ]
3-(benzylamino)-1-(4-chlorophenyl)propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	Stage #1: vinyl magnesium bromide; 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: benzylamine With water In tetrahydrofuran at 20℃;

Reference： [1]Location in patent: experimental part Hari, Yoshiyuki; Yokoyama, Takuya; Aoyama, Toyohiko [Heterocycles, 2010, vol. 80, # 1, p. 679 - 687]

40
[ 616-47-7 ]
[ 122334-37-6 ]
(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.6%	Stage #1: 1-methyl-1H-imidazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.916667h; Inert atmosphere; Stage #2: With triethylsilyl chloride In tetrahydrofuran; hexane at -78℃; for 2h; Stage #3: 4-chloro-N-methoxy-N-methylbenzamide Further stages;

Reference： [1]Chennamaneni, Naveen Kumar; Arif, Jenifer; Buckner, Frederick S.; Gelb, Michael H. [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 23, p. 6582 - 6584]

41
[ 108-36-1 ]
[ 122334-37-6 ]
[ 75762-56-0 ]

Yield	Reaction Conditions	Operation in experiment
23%	Stage #1: 1,3-dibromobenzene With iodine; magnesium In diethyl ether at 20 - 30℃; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In diethyl ether at 0 - 20℃; Inert atmosphere;

Reference： [1]Kishore Kumar; Chavarria, Gustavo E.; Charlton-Sevcik, Amanda K.; Arispe, Wara M.; MacDonough, Matthew T.; Strecker, Tracy E.; Chen, Shen-En; Siim, Bronwyn G.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 4, p. 1415 - 1419]

42
[ 106-37-6 ]
[ 122334-37-6 ]
[ 27428-57-5 ]

Yield	Reaction Conditions	Operation in experiment
19%	Stage #1: 1.4-dibromobenzene With iodine; magnesium In diethyl ether at 20 - 30℃; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In diethyl ether at 0 - 20℃; Inert atmosphere;

Reference： [1]Kishore Kumar; Chavarria, Gustavo E.; Charlton-Sevcik, Amanda K.; Arispe, Wara M.; MacDonough, Matthew T.; Strecker, Tracy E.; Chen, Shen-En; Siim, Bronwyn G.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 4, p. 1415 - 1419]

43
[ 122334-37-6 ]
[ 1655-07-8 ]
[ 947309-61-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl 2-oxocyclohexane carboxylate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran for 18h;	1 Example 1; 3-(4-chloro-phenyl)-2-(2>4-dichloro-phenyl)-4,5,6,7-tetraliydro-2H- indazole-7-carboxylic acidpiperidin-1-ylamide (Cpd 33); To a solution of LHMDS (21 mL, 2.1 mmol) in 50 mL of anhydrous THF under a nitrogen atmosphere at -78 0C was added 2-oxo-cyclohexanecarboxylic acid ethyl ester Compound Ia (1.80 g, 10.0 mmol) in 10 mL of anhydrous THF. The resultant homogeneous mixture was left to stir at -78 0C for 40 min followed by the drop wise addition of 4-chloro-N-methoxy-N-methyl-benzamide Compound Ib (2.0 g, 10 mmol) in 10 mL of anhydrous THF. The reaction mixture was allowed to stir for 18 hours and allowed to warm to ambient temperature. The reaction mixture was quenched with water (50 mL) and the organic layer was extracted with EtOAc (200 mL) and washed with brine, separated and dried with anhydrous Na2SO4, then filtered and concentrated in vacuo to yield 3-(4-chloro-benzoyl)-2-oxo-cyclohexanecarboxylic acid ethyl ester Compound Ic (1.7 g) as an oil, which was used in the next step without further purification.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2007/95513, 2007, A1 Location in patent: Page/Page column 52

44
[ 106-39-8 ]
[ 14040-11-0 ]
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
76%	With dmap; potassium phosphate; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 120℃; for 0.333333h; Microwave irradiation;

Reference： [1]Wieckowska, Anna; Fransson, Rebecca; Odell, Luke R.; Larhed, Mats [Journal of Organic Chemistry, 2011, vol. 76, # 3, p. 978 - 981]

45
[ 122334-37-6 ]
[ 623-03-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78℃; for 1.5h; Inert atmosphere; Stage #2: With ammonia; iodine In tetrahydrofuran; hexane; water at 0 - 20℃; Inert atmosphere;	4.2. Typical experimental procedure for the conversion of N,N-dialkyl amides (1) into nitriles (2) General procedure: To a solution of N,N-dimethyl benzamide (298 mg, 2 mmol) in dry THF (4 mL) was added DIBAL-H (1.04 M in hexane, 2.3 mL, 1.2 equiv) at -78 °C. The mixture was stirred for 1.5 h under an argon atmosphere at from -70 °C to -40 °C slowly. Then, aq NH3 (concentration: 28.0-30.0%, 4 mL) and I2 (762 mg, 3.0 equiv) were added at 0 °C, and the reaction mixture was stirred for 2 h at room temperature. Reaction mixture was poured into saturated aq Na2SO3 solution (10 mL) and extracted with ethyl acetate (15 mL×3). The organic layer was dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was purified by short column chromatography on silica gel (eluent: hexane/ethyl acetate=4:1) to afford benzonitrile in 67% yield (138 mg).Most of the present prepared nitriles are commercially available and they are identified with authentic nitrile compounds.

Reference： [1]Location in patent: experimental part Suzuki, Yusuke; Yoshino, Takumi; Moriyama, Katsuhiko; Togo, Hideo [Tetrahedron, 2011, vol. 67, # 21, p. 3809 - 3814]

46
[ 70298-88-3 ]
[ 122334-37-6 ]
[ 1322800-15-6 ]

Reference： [1]Helvetica Chimica Acta,2012,vol. 95,p. 556 - 563

47
[ 626-55-1 ]
[ 122334-37-6 ]
[ 14548-44-8 ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: 3-Bromopyridine With n-butyllithium In diethyl ether; hexane at -70 - -60℃; for 1.5h; Inert atmosphere; Cooling with acetone-dry ice; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; diethyl ether; hexane at -70 - 20℃; for 4.5h; Inert atmosphere; Cooling with acetone-dry ice;

Reference： [1]Keenan, Martine; Abbott, Michael J.; Alexander, Paul W.; Armstrong, Tanya; Best, Wayne M.; Berven, Bradley; Botero, Adriana; Chaplin, Jason H.; Charman, Susan A.; Chatelain, Eric; Von Geldern, Thomas W.; Kerfoot, Maria; Khong, Andrea; Nguyen, Tien; McManus, Joshua D.; Morizzi, Julia; Ryan, Eileen; Scandale, Ivan; Thompson, R. Andrew; Wang, Sen Z.; White, Karen L. [Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4189 - 4204]

48
[ 6952-59-6 ]
[ 122334-37-6 ]
[ 35256-77-0 ]

Yield	Reaction Conditions	Operation in experiment
26%	With n-butyllithium In tetrahydrofuran; hexane Inert atmosphere;	4.2.17. 3-(2-Methoxybenzoyl)benzonitrile (13a) General procedure: To a solution of compound 9a (2.0 g, 10.2 mmol) and 3-bromobenzonitrile 10 (1.86 g, 10.2 mmol) in anhydrous THF was added dropwise n-BuLi (2.0 M solution in n-hexane, 10.2 mL, 20.5 mmol) at -78 °C under Ar. After the addition of n-BuLi, the solution was poured into ice-cold 1 M HCl, and the organic phase was extracted with AcOEt, washed with brine twice, and dried over Na2SO4. Then, the solvent was removed under reduced pressure and the resulting brown oil was purified by silica-gel column chromatography (n-hexane:EtOAc = 5:1) to yield the benzophenone derivative 13a as a white solid (457 mg, 19%).

Reference： [1]Location in patent: experimental part Hayashi, Yoshio; Yamazaki, Yuri; Sumikura, Makiko; Masuda, Yurika; Hayashi, Yoshiki; Yasui, Hiroyuki; Kiso, Yoshiaki; Chinen, Takumi; Usui, Takeo; Yakushiji, Fumika; Potts, Barbara; Neuteboom, Saskia; Palladino, Michael; Lloyd, George Kenneth [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4279 - 4289]

49
[ 3277-89-2 ]
[ 122334-37-6 ]
[ 5739-37-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	In tetrahydrofuran at 20℃; for 2h; Cooling with ice;	2 Representative standard procedures for the synthesis of ketones 12 General procedure: To an ice-cold solution of theWeinreb amide (2.0 mmol) in 8mL of anhydrous THF was added dropwise a solution of alkyl magnesium bromide (2.1 mmol) in THF. The mixture stirred at the same temperature for 2 h. The reaction was quenched by addition of an aqueous 10% HCl solution (15 mL) and stirred for 5 min. The resulting solution was extracted with EtOAc and the combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated under vacuum after filtration. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to offer the pure product 12. 4.1.2.2 1-(4-Chlorophenyl)-3-phenylpropan-1-one 12e According to the representative procedure above, the title compound was obtained as a white solid (1.1 g, 90%) from the corresponding amide (5 mmol). Rf = 0.65 (petroleum ether/EtOAc 3:1); m.p. = 69 °C; IR (KBr): = 3025, 2924, 1681, 1586, 1485, 1396, 1204, 1093 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.92-7.88 (m, 2H), 7.46-7.42 (m, 2H), 7.20-7.32 (m, 5H), 3.31-3.26 (m, 2H), 3.10-3.00 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): δ = 198.0, 141.1, 139.5, 135.2, 129.5, 129.0, 128.6, 128.5, 126.3, 40.5, 30.1 ppm; MS (E.I., 70 eV) m/z 244, 209, 141, 139 (100), 113, 111, 105, 104, 103, 91, 77, 75.

Reference： [1]Gembus, Vincent; Furman, Christophe; Millet, Régis; Mansouri, Roxane; Chavatte, Philippe; Levacher, Vincent; Brière, Jean-François [European Journal of Medicinal Chemistry, 2012, vol. 58, p. 396 - 404]

50
[ 122334-37-6 ]
[ 566945-71-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; [bis(acetoxy)iodo]benzene; trifluoroacetic acid; trifluoroacetic anhydride at 50℃; for 16h; Sealed tube; chemoselective reaction;
81%	With iodobenzene; [Ru(OAc)2(p-cymene)]; tert-butylammonium hexafluorophosphate(V); trifluoroacetic acid; trifluoroacetic anhydride at 50℃; Electrochemical reaction;
79%	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide With dirhodium tetraacetate; triethylamine triflouroacetate; trifluoroacetic acid; trifluoroacetic anhydride at 20℃; Electrolysis; Inert atmosphere; Schlenk technique; Stage #2: With water; sodium hydrogencarbonate Inert atmosphere; Schlenk technique;

Reference： [1]Yang, Fanzhi; Ackermann, Lutz [Organic Letters, 2013, vol. 15, # 3, p. 718 - 720]
[2]Massignan, Leonardo; Tan, Xuefeng; Meyer, Tjark H.; Kuniyil, Rositha; Messinis, Antonis M.; Ackermann, Lutz [Angewandte Chemie - International Edition, 2020, vol. 59, # 8, p. 3184 - 3189][Angew. Chem., 2020, vol. 132, p. 3210 - 3215,6]
[3]Tan, Xuefeng; Massignan, Leonardo; Hou, Xiaoyan; Frey, Johanna; Oliveira, João C. A.; Hussain, Masoom Nasiha; Ackermann, Lutz [Angewandte Chemie - International Edition, 2021, vol. 60, # 24, p. 13264 - 13270][Angew. Chem., 2020, vol. 133, p. 13373 - 13379,7]

51
[ 109-06-8 ]
[ 122334-37-6 ]
[ 10420-99-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: α-picoline With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78℃; for 3h; Inert atmosphere;

Reference： [1]Muir, Calum W.; Kennedy, Alan R.; Redmond, Joanna M.; Watson, Allan J. B. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 20, p. 3337 - 3340]

52
[ 1126-46-1 ]
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: Methyl 4-chlorobenzoate; N,O-dimethylhydroxylamine*hydrochloride In tetrahydrofuran at -20℃; for 0.0833333h; Inert atmosphere; Stage #2: With isopropylmagnesium chloride In tetrahydrofuran; diethyl ether at -20℃; for 0.416667h; Inert atmosphere;

Reference： [1]Muir, Calum W.; Kennedy, Alan R.; Redmond, Joanna M.; Watson, Allan J. B. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 20, p. 3337 - 3340]

53
[ 925-90-6 ]
[ 122334-37-6 ]
[ 6285-05-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	In diethyl ether at 0℃; for 3h;	1-(4-chlorophenyl)Propan-1-one [0117] l-(4-chlorophenyl)Propan-l-one: 4-Chloro-N-methoxy-N-methylbenzamide (0.5352 g, 2.68 mmol, 1.00 equiv) was dissolved in Et20 (10 mL) and cooled to 0 °C. Ethylmagnesium bromide (1.80 mL, 5.36 mmol, 2.00 equiv, 3M solution in Et20) was added dropwise. After stirring for 3 h the reaction was quenched with NH4C1 (sat. aq.) and the layers were separated. The aqueous layer was back extracted with Et20 (3x). The combined organic layers were washed with H20, brine, dried over Na2S04, filtered and concentrated. Purification by silica gel column chromatography using a 1 : 1 mixture of ethyl acetate in hexanes as eluant furnished the title compound (0.349 g) as a clear oil. Yield: 77%. The spectral data was identical to that reported in the literaturev: NMR (500 MHz, CDC13): δ 7.94-7.89 (m, 2H), 7.49-7.38 (m, 2H), 2.97 (q, J= 7.2 Hz, 2H), 1.22 (t, J= 7.2 Hz, 3H) ppm.

Reference： [1]Current Patent Assignee: UNIVERSITY OF PENNSYLVANIA - WO2014/47257, 2014, A2 Location in patent: Paragraph 0117

54
[ 1003-21-0 ]
[ 122334-37-6 ]
(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 1: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.
		Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 min, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 18, step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound
		Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 8: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.

		Intermediate 1: step b (4-Ciloropienyl)(l-metiyl-lH-iBidazol-5-yl)siietiaHOie Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-bromo-l -methyl- l H-imidazole (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 min, then was again cooled in an ice bath before addition of 4-chloro-A'-methoxy-A'-methyibenzamide (10.7 g, 53.6 mmol, intermediate 1 : step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous N.H4CI and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHC03. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2S04), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAcrheptanes (1 : 1 , 150 mL). The precipitated solid was collected by vacuum filtration and washed with heptanes to afford the title compound.
		10180] Ethyl magnesium bromide (3.0 M in diethyl ether,21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-bromo-i-methyl- 1H-imidazole (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 mm, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N- methylbenzamide (10.7 g, 53.6 mmol, Intermediate 1: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4C1 and diluted with watet The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HC1, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2504), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration and washed with heptanes to afford the title compound.
		Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 43: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.
		Intermediate 43: step b (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-bromo-l -methyl- IH-imidazoie (10.4 g, 64.4 nimol) i THF (100 niL) under a. nitrogen atmosphere in an ice bath, A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled i an ice bath before addition of 4-chloro-N-methoxy-A'r-mefhyibenzamide (10.7 g, 53.6 mmol, Intermediate 43: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4CI and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHC(. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2S0 ), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of F,tOAc:heptanes (1 : 1 , 150 ml,). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.
		intermediate 8: step b(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanoneEthyl magnesium bromide (3,0 M in diethyl ether, 21 .5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-brom.o-l -methyl-lH-imidazole (10.4 g, 64.4 mmol) in TFIF (100 mL) under a nitrogen atmosphere in an ice bath, A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, intermediate 8: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NuEta4Omicron and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HQ, then neutralized with saturated aqueous NaHCC . The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried ( a2S04), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtQAc: heptanes (1 : 1 , 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound
		Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 22: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.
		Ethylmagnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a period of several minutes in an ice bath under nitrogen atmosphere to a solution of <strong>[1003-21-0]5-bromo-1-methyl-1H-imidazole</strong> G, 64.4 mmol). A white precipitate was formed upon addition. The mixture was removed from the ice bath, stirred for 20 min and then cooled again in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, intermediate 1: step a) . The resulting white suspension was stirred at room temperature overnight. The reaction was quenched by the addition of a saturated aqueous NH4Cl solution and diluted with water. The mixture was partially concentrated, the THF was removed and diluted with DCM. The mixture was acidified to pH 1 with 1 N HCl aqueous solution and then neutralized with saturated aqueous NaHCO3 solution. The phases were separated and the aqueous phase further extracted with DCM. The organic extracts were washed with water, then dried (Na2SO4), filtered and concentrated to give a white solid. The crude product was triturated with a mixture of EtOAc: heptane (1: 1, 150 mL). The precipitated solid was collected by vacuum filtration and washed with heptane to give the title compound.

Reference： [1]Patent: US2014/107094,2014,A1 .Location in patent: Paragraph 0377; 0378
[2]Patent: US2014/107097,2014,A1 .Location in patent: Paragraph 0312; 0313
[3]Patent: US2015/105404,2015,A1 .Location in patent: Paragraph 0227
[4]Patent: WO2015/57200,2015,A1 .Location in patent: Page/Page column 38; 39
[5]Patent: US2015/105365,2015,A1 .Location in patent: Paragraph 0179; 0180
[6]Patent: US2015/105366,2015,A1 .Location in patent: Paragraph 0405; 0406
[7]Patent: WO2015/57205,2015,A1 .Location in patent: Page/Page column 113; 114
[8]Patent: WO2015/57203,2015,A1 .Location in patent: Page/Page column 58
[9]Patent: US2015/111870,2015,A1 .Location in patent: Paragraph 0413; 0414
[10]Patent: KR2016/70823,2016,A .Location in patent: Paragraph 0165-0168
[11]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2047 - 2057

55
[ 24134-09-6 ]
[ 122334-37-6 ]
[ 235092-30-5 ]

Yield	Reaction Conditions	Operation in experiment
		To a 50-mL round-bottom flask containing a solution of <strong>[24134-09-6]5-bromo-1,2-dimethyl-1H-imidazole</strong> (440 mg, 2.51 mmol, Intermediate 24, step a) and THF (20 mL) under nitrogen was added isopropylmagnesium chloride in THF (2.0 M, 1.2 mL, 2.4 mmol) dropwise. The mixture was stirred for 0.5 hours at room temperature, and a solution of 4-chloro-N-methoxy-N-methylbenzamide (500 mg, 2.50 mmol, Intermediate 18, step a) in THF (5 mL) was introduced. After stirring for 7.5 hours at room temperature, the reaction was quenched by addition of 10 mL of EtOH, and concentrated under vacuum. The residue was purified by flash column chromatography (silica gel, 50% EtOAc in petroleum, 0-10% MeOH in CH2Cl2) to give the title compound as a white solid.

Reference： [1]Patent: US2014/107097,2014,A1 .Location in patent: Paragraph 0334; 0335

56
[ 122334-37-6 ]
[ 35822-58-3 ]
[ 23864-94-0 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 16748 - 16751

57
[ 122334-37-6 ]
[ 35822-58-3 ]
(S)-3-(4-chlorophenyl)-1,3-dihydro-2-benzofuran-1-one [ No CAS ]
3‐(4‐chlorophenyl)isobenzofuran‐1(3H)‐one [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 16748 - 16751

58
[ 6638-79-5 ]
[ 873-76-7 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With tert.-butylhydroperoxide; copper(II) acetate monohydrate; calcium carbonate In acetonitrile at 80℃; for 24h;	Oxidative Synthesis of Weinreb Amides 3 from Benzyl Alcohols 1 and N,O-Dimethylhydroxylamine Hydrochloride Salt (2); General Procedure General procedure: An oven-dried 15 mL glass vial with a magnetic stirrer bar was charged with Cu(OAc)2·H2O (12 mg, 6 mol%), N,O-dimethylhydroxylamine hydrochloride (2; 117 mg, 1.2 mmol), the respective benzyl alcohol 1 (1 mmol), aq 70% TBHP (0.17 mL, 1.2 mmol), CaCO3 (120 mg, 1.2 mmol) in MeCN (1 mL). The glass vial was flushed with N2 three times and the contents were stirred at r.t. for 1 h. Then the reaction mixture was stirred for 24 h at 80 °C. After completion of the reaction, the mixture was cooled to r.t. All volatiles were removed under vacuum. The product was extracted with EtOAc (20 mL) and the organic layer was washed with sat. aq NaHCO3 (20 mL), dried (Na2SO4), and the solvent removed under vacuum. The Weinreb amide product 3 was purified by column chromatography (silica gel, 100-200 mesh) using a gradient of petroleum ether (bp 60-80 °C) and EtOAc. All the amides were identified by GC-MS, 1H, and 13C NMR spectroscopic analysis.

Reference： [1]Yedage, Subhash L.; Bhanage, Bhalchandra M. [Synthesis, 2015, vol. 47, # 4, p. 526 - 532]

59
[ 122334-37-6 ]
[ 104-88-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide With chloromagnesium dimethylaminoborohydride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: With acetaldehyde; acetic acid In tetrahydrofuran; pentane for 0.25h; Inert atmosphere; Further stages;
	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide With chloromagnesium dimethylaminoborohydride In tetrahydrofuran at 25℃; for 0.5h; Inert atmosphere; Stage #2: With acetaldehyde; acetic acid In tetrahydrofuran; pentane for 0.25h; Inert atmosphere;	General Procedure for the Reduction of Weinreb Amides to Aldehydes. General procedure: The following procedure for the reduction of N-methoxy-N-methylbenzamide by MgAB is representative. To an oven-dried and argon cooled 25-mL round-bottom flask equippedwith a stir bar and septa was added N-methoxy-N-methylbenzamide (0.305 mL, 2 mmol)followed by THF (1.7 mL). Chloromagnesium dimethylaminoborohydride (MgAB, 2mL, 1M, 2 mmol) was then added dropwise via a syringe. The reaction was monitored byTLC (Hex/EtOAc, 1:1). After 30 min, the reaction solution was added dropwise to a solution of acetaldehyde (2 mmol) and acetic acid (2 mmol) in pentane (10 mL). After 15min, saturated aqueous NH4Cl (2 mL) was added. The organic layer was separated and the aqueous phase was extracted with Et2O (2 x 10 mL). The combined organic layerswas washed with 1M HCl (10 mL), dried with magnesium sulfate, and concentratedunder reduced pressure to yield crude aldehyde as an orange oil. The crude aldehyde (2mmol) was transferred to a round-bottom flask equipped with a magnetic stir barfollowed by EtOH (3 mL) and EtOAc (5 mL) and cooled with an ice bath. A saturated aqueous solution of NaHSO3 (1 mL) was added with stirring. After 4 h, the solid bisulfite adduct was isolated by vacuum filtration, washed with Et2O (3 × 5 mL) and dried undervacuum to yield a white solid. The bisulfite adduct was then added to a round-bottom flask dissolved in H2O (10 mL) and a 37% formalin solution (2 mL) was added followedby Et2O (20 mL). The biphasic solution was stirred for 1 h. The aqueous layer was separated and extracted with a 1:1 mixture of THF/Et2O (3 x 10 mL). The combined organic layers was dried over magnesium sulfate, and concentrated under reduced pressure to give the aldehyde as a pale yellow oil (0.160 g, 1.5 mmol 75% yield).

Reference： [1]Bailey, Christopher L.; Joh, Alexander Y.; Hurley, Zefan Q.; Anderson, Christopher L.; Singaram, Bakthan [Journal of Organic Chemistry, 2016, vol. 81, # 9, p. 3619 - 3628]
[2]Bailey, Christopher L.; Clary, Jacob W.; Tansakul, Chittreeya; Klabunde, Lucas; Anderson, Christopher L.; Joh, Alexander Y.; Lill, Alexander T.; Peer, Natalie; Braslau, Rebecca; Singaram, Bakthan [Tetrahedron Letters, 2015, vol. 56, # 5, p. 706 - 709]

60
[ 673-32-5 ]
[ 122334-37-6 ]
(E)-1-(4-chlorophenyl)-2-methyl-3-phenylprop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With titanium(IV) isopropylate; isopropylmagnesium chloride In diethyl ether at 20℃; for 4.08333h; Inert atmosphere; regioselective reaction;

Reference： [1]Silwal, Sajan; Rahaim, Ronald J. [Journal of Organic Chemistry, 2014, vol. 79, # 17, p. 8469 - 8476]

61
Ν,Ο-dimethylhydroxylamine hydrochloride [ No CAS ]
[ 122-01-0 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 20℃; for 72h;	1.a Intermediate 1: Step a4-Chloro-N-methoxy-N-methylbenzamide 10178] Pyridine (27.6 mL, 343 mmol) was added to N,Odimethylhydroxylamine hydrochloride (16.7 g, 172 mmol) in DCM (400 mL). 4-Chlorobenzoyl chloride (20 mL, 156 mmol) was then added and the mixture was stirred at room temperature for 3 days. Solids were removed by vacuum filtration and washed with DCM. The filtrate was washed with 1 N aqueous HC1 followed by watet The organic phase was dried (Na2504), filtered, and concentrated, affording the crude title compound as a colorless liquid which was used without purification in the next step.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2015/105365, 2015, A1 Location in patent: Paragraph 0177; 0178

62
[ 141-32-2 ]
[ 122334-37-6 ]
butyl (E)-3-(5-chloro-2-(methoxy(methyl)carbamoyl)phenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With silver hexafluoroantimonate; tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer In chlorobenzene at 80℃; Irradiation;

Reference： [1]Fabry, David C.; Zoller, Jochen; Raja, Sadiya; Rueping, Magnus [Angewandte Chemie - International Edition, 2014, vol. 53, # 38, p. 10228 - 10231][Angew. Chem., 2014, vol. 126, # 38, p. 10392 - 10396,5]

63
[ 1942-45-6 ]
[ 122334-37-6 ]
[ 100-52-7 ]
2-(4-chlorophenyl)-5-phenyl-3,4-dipropylfuran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	Stage #1: 4-Octyne; 4-chloro-N-methoxy-N-methylbenzamide With titanium(IV) isopropylate; isopropylmagnesium chloride In diethyl ether at 20℃; for 4h; Inert atmosphere; Stage #2: benzaldehyde With boron trifluoride diethyl etherate In diethyl ether at -78 - 20℃; for 2h; Inert atmosphere;	General Procedure A General procedure: A dry round-bottom flask under an atmosphere of argon was charged with alkyne (1 mmol), Weinreb amide (1.2 mmol), Ti(OiPr)4 (1.5 mmol, 0.44 mL), and anhydrous Et2O (10 mL). To this stirring mixture was injected i-PrMgCl (2M in Et2O, 3 mmol, 1.5 mL) dropwise over 5 minutes, the reaction was stirred for 4 hours at room temperature. The round-bottom flask was then placed in a dry-ice acetone bath and equilibrated to -78 °C. In a separate dry pear-shaped flask under an atmosphere of argon BF3•OEt2 (2 mmol, 0.247 mL) was injected into a solution of aldehyde (2 mmol) in Et2O (2 mL) precooled with a dry-ice acetone bath. The BF3•OEt2-aldehyde mixture was stirred for 30 seconds then pulled up into a syringe. The solution of complexed aldehyde was then injected into the cooled reaction mixture containing the titanacycle. The cooling bath was removed and the reaction was allowed to warm to room temperature over 2 hours. At which point the reaction was quenched with 1 mL H2O, dried over magnesium sulfate, filtered, and concentrated. The crude material was subjected to flash chromatography (hexanes/CH2Cl2: 90/10).

Reference： [1]Silwal, Sajan; Rahaim, Ronald J. [Tetrahedron Letters, 2015, vol. 56, # 42, p. 5738 - 5742]

64
[ 106-39-8 ]
[ 61117-58-6 ]
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 1h; Sealed tube;	General procedure: A mixture of arylhalide (I, Br) (1 mmol), Weinreb amine hydrochloride(1.5 mmol), Pd(OAc)2 (5 mol %), xantphos (6 mol %), triethylamine (3 mmol), and cobalt carbonyl (0.3 mmol) in 1,4-dioxane was heated at 90 °C for 1h in a septum-closed sealed tube. After cooling, the reaction mixture was concentrated in vacuum and the residue was extracted with ethylacetate and water. The ethylacetate layer was concentrated and the residue obtained was purified by flash column chromatography to get the desired product. Note: Carbon monoxide gas is highly toxic and should be handled by trained professionals in a well-ventilated fumehood with appropriate ventilation. In all the reactions, Co2(CO)8 was handled carefully in fumehoods using appropriate personal protective clothing and equipment.

Reference： [1]Baburajan, Poongavanam; Elango, Kuppanagounder P. [Synthetic Communications, 2015, vol. 45, # 4, p. 541 - 548]

65
[ 61117-58-6 ]
[ 637-87-6 ]
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 1h; Sealed tube;	General procedure: A mixture of arylhalide (I, Br) (1 mmol), Weinreb amine hydrochloride(1.5 mmol), Pd(OAc)2 (5 mol %), xantphos (6 mol %), triethylamine (3 mmol), and cobalt carbonyl (0.3 mmol) in 1,4-dioxane was heated at 90 °C for 1h in a septum-closed sealed tube. After cooling, the reaction mixture was concentrated in vacuum and the residue was extracted with ethylacetate and water. The ethylacetate layer was concentrated and the residue obtained was purified by flash column chromatography to get the desired product. Note: Carbon monoxide gas is highly toxic and should be handled by trained professionals in a well-ventilated fumehood with appropriate ventilation. In all the reactions, Co2(CO)8 was handled carefully in fumehoods using appropriate personal protective clothing and equipment.

Reference： [1]Baburajan, Poongavanam; Elango, Kuppanagounder P. [Synthetic Communications, 2015, vol. 45, # 4, p. 541 - 548]

66
[ 7103-09-5 ]
[ 122334-37-6 ]
[ 35204-91-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	In tetrahydrofuran at -20 - 20℃;

Reference： [1]Davies, Jacob; Booth, Samuel G.; Essafi, Stephanie; Dryfe, Robert A. W.; Leonori, Daniele [Angewandte Chemie - International Edition, 2015, vol. 54, # 47, p. 14017 - 14021][Angew. Chem., 2015, vol. 127, # 47, p. 14223 - 14227,5]

67
6-bromo-4-tert-butoxyquinazoline [ No CAS ]
[ 122334-37-6 ]
(4-tert-butoxyquinazolin-6-yl)(4-chlorophenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6-bromo-4-tert-butoxyquinazoline With n-butyllithium In tetrahydrofuran at -78℃; for 0.666667h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at 0℃; for 0.5h;	2.2 Step 2: (4-tert-Butoxyquinazolin-6-yl)(4-chlorophenyl)methanone Into a 250-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-bromo-4-(tert-butoxy)quinazoline (2.5 g, 8.89 mmol, 1.00 equiv) in tetrahydrofuran (100 mL). This was followed by the addition of n-BuLi (4.25 mL, 1.20 equiv) dropwise with stirring at -78° C. After 40 mins, to the mixture was added a solution of 4-chloro-N-methoxy-N-methylbenzamide (2.17 g, 10.87 mmol, 1.20 equiv) in tetrahydrofuran (20 mL). The resulting solution was stirred for another 30 min at 0° C. in a water/ice bath. The reaction was then quenched by the addition of water (10 mL), and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5), to yield of 4-(tert-butoxy)-6-[(4-chlorophenyl)carbonyl]quinazoline as a white solid.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2016/68512, 2016, A1 Location in patent: Paragraph 0291

68
[ 122334-37-6 ]
[ 107-30-2 ]
[ 30780-45-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With 4,4'-di-tert-butylbiphenyl; lithium In tetrahydrofuran; mineral oil at -78℃; for 2.5h; Inert atmosphere; Schlenk technique;

Reference： [1]Pace, Vittorio; Murgia, Irene; Westermayer, Sophie; Langer, Thierry; Holzer, Wolfgang [Chemical Communications, 2016, vol. 52, # 48, p. 7584 - 7587]

69
[ 122334-37-6 ]
[ 501-65-5 ]
[ 1315257-11-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With silver hexafluoroantimonate; [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; copper(II) acetate monohydrate at 100℃; for 12h; Green chemistry;

Reference： [1]Yedage, Subhash L.; Bhanage, Bhalchandra M. [Green Chemistry, 2016, vol. 18, # 20, p. 5635 - 5642]

70
5-bromo-1-(oxan-2-yl)-3-[1-trifluoromethanesulfonylpiperidin-4-yl]-1H-indazole [ No CAS ]
[ 122334-37-6 ]
5-[(4-chlorophenyl)carbonyl]-1-(oxan-2-yl)-3-[1-trifluoromethanesulfonylpiperidin-4-yl]-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-bromo-1-(oxan-2-yl)-3-[1-trifluoromethanesulfonylpiperidin-4-yl]-1H-indazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;	PH-41.2 Step 2: Synthesis of 5-[(4-chlorophenyl)carbonyl]-1-(oxan-2-yl)-3-[1-trifluoromethanesulfonylpiperidin-4-yl]-1H-indazole Into a 100-mL oven-dried round-bottom flask under nitrogen, was placed a solution of 5-bromo-1-(oxan-2-yl)-3-[1-(trifluoromethane) sulfonylpiperidin-4- yl]-1 H-indazole (4.96 g, 9.99 mmol) in tetrahydrofuran (30 mL), followed by dropwise addition of a 2.5 solution of BuLi in hexanes (4.4 mL, 11.0 mmol) at -78°C. After 30 min at -78°C, a solution of 4-chloro-N-methoxy-N- methylbenzamide (2,0 g, 10,02 mmol) in tetrahydrofuran (5 mL) was added dropwise, and the resulting solution was stirred under nitrogen overnight at room temperature. After addition of water (100 mL), the mixture was extracted with ethyl acetate (3x50 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by recrystailization from petroleum ether-Et20 to yield 5-[(4- chiorophenyl) carbonyl]-1-(oxan-2-yl)-3-[1-(trifluoromethane) sulfonylpiperidin- 4-yl]-1 H-indazole as a white solid. LC/ S (ES, m/z): 556 [M+H]+.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2017/34872, 2017, A1 Location in patent: Page/Page column 141

71
[ 407-14-7 ]
[ 122334-37-6 ]
[ 87996-55-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-4-(trifluoromethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at 20℃; for 5h; Inert atmosphere;	PH-1.8 Step 8: Synthesis of (4-chlorophenyl)[4-trifluoromethoxyphenyl]methanone Into a 250-mL oven-dried round-bottom flask purged and maintained nitrogen, was placed a solution of 1-bromo-4-(trifluoromethoxy)benzene (5.0 g, 20.8 mmol) in tetrahydrofuran (60 mL), followed by dropwise addition of 2.5 M solution of n-BuLi in hexanes (9.2 mL, 23.0 mmol) at -78°C. After 30 min, a solution of 4-chloro-N-methoxy-N-methylbenzamide (4.15 g, 20,8 mmol) in tetrahydrofuran (20 mL) was added. The resulting solution was stirred for 5 h at room temperature, and then saturated sodium bicarbonate solution (150 mL) was added. The mixture was extracted with ethyl acetate (3x150 mL). The combined organic extract was dried over sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eiuted with ethyl acetate/petroleum ether (0:100-1 :20) to yield (4-chlorophenyl)[4- (trifluoromethoxy)phenyl]methanone as a white solid.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2017/34872, 2017, A1 Location in patent: Page/Page column 98; 100; 101

72
[ 122334-37-6 ]
[ 536975-49-2 ]
1-(4-chlorophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 4-chloro-N-methoxy-N-methylbenzamide With tetrabutylammonium triphenyldifluorosilicate In toluene at 20℃; for 0.166667h; Stage #2: phenyl (trimethylsilyl)difluoromethyl sulfide In toluene at 0 - 20℃; for 2h; Inert atmosphere;

Reference： [1]Phetcharawetch, Jongkonporn; Betterley, Nolan M.; Soorukram, Darunee; Pohmakotr, Manat; Reutrakul, Vichai; Kuhakarn, Chutima [European Journal of Organic Chemistry, 2017, vol. 2017, # 46, p. 6840 - 6850]

73
[ 122334-37-6 ]
2-bromo-4-chloro-N-methoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With N-Bromosuccinimide; palladium diacetate; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane Inert atmosphere; Sealed tube; regioselective reaction;

Reference： [1]Das, Riki; Kapur, Manmohan [Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126]

74
[ 122334-37-6 ]
[ 646528-36-1 ]

Yield	Reaction Conditions	Operation in experiment
49%	With N-chloro-succinimide; palladium diacetate; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane Inert atmosphere; Sealed tube; regioselective reaction;

Reference： [1]Das, Riki; Kapur, Manmohan [Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126]

75
[ 15022-08-9 ]
[ 122334-37-6 ]
2-allyl-4-chloro-N-methoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With carbonyl(η-5-cyclopentadienyl)diiodocobalt(III); silver(I) acetate; silver(I) triflimide at 70℃; for 24h; Inert atmosphere; Glovebox;

Reference： [1]Kawai, Kentaro; Bunno, Youka; Yoshino, Tatsuhiko; Matsunaga, Shigeki [Chemistry - A European Journal, 2018, vol. 24, # 40, p. 10231 - 10237]

76
[ 80204-20-2 ]
[ 122334-37-6 ]
[ 123989-29-7 ]

Yield	Reaction Conditions	Operation in experiment
88.2%	Stage #1: 1-bromo-1-cyclopropylethane With magnesium In tetrahydrofuran at 20℃; for 3h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -20℃; for 3h;	2; 9 Embodiment 9 In a dry round bottom flask is added in excess of the cutting and 1000 ml tetrahydrofuran, then dropwise 1 - bromo ethyl cyclopropane (1 µM), the resulting mixture at room temperature under stirring for 3 hours, the reaction is filtered, to remove the magnesium chips, formula (II) compound of tetrahydrofuran solution (1 mol/L). The reaction is as followsThe embodiment 1 to obtain the compounds of formula (I) compound structure (0.10 µM), tetrahydrofuran (250 ml) are added to a reaction in the bottle, in the -20 °C dropping embodiment 2 of formula (II) to obtain a compound of tetrahydrofuran solution 100 ml, then completing, at this temperature to continue the reaction [...] 3 hr, the reaction after the reaction is dropped to 250 ml with cold water, then completing, filtering to remove the solid, the collection of organic phase, drying and reducing pressure concentration and crystallization, shall be 1 - (4 - chlorophenyl) -2 - cyclopropyl -1 - acetone product 18.4 g, in formula (I) compounds of structure the idea receives rate is 88.2%, HPLC purity through detection of 99.3%.

Reference： [1]Current Patent Assignee: SHANDONG RAINBOW INVESTMENT CO., LTD. - CN108610246, 2018, A Location in patent: Paragraph 0015; 0021

77
[ 65864-64-4 ]
[ 122334-37-6 ]
[ 655-54-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium 2-methylbutan-2-olate In tetrahydrofuran; cyclohexane at 0℃; for 4h; Inert atmosphere; chemoselective reaction;

Reference： [1]Miele, Margherita; Citarella, Andrea; Micale, Nicola; Holzer, Wolfgang; Pace, Vittorio [Organic Letters, 2019, vol. 21, # 20, p. 8261 - 8265]

78
[ 122334-37-6 ]
1-(4-chlorophenyl)pent-4-en-1-one O-methyl oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran / 2 h / Inert atmosphere; Reflux 1.2: -10 - 20 °C / Inert atmosphere 2.1: sulfuric acid / ethanol / 20 °C / Inert atmosphere

Reference： [1]Huang, Fei; Zhang, Songlin [Organic Letters, 2019, vol. 21, # 18, p. 7430 - 7434]

79
[ 122334-37-6 ]
5-(4-chlorophenyl)-2-methyl-3,4-dihydro-2H-pyrrole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: magnesium / tetrahydrofuran / 2 h / Inert atmosphere; Reflux 1.2: -10 - 20 °C / Inert atmosphere 2.1: sulfuric acid / ethanol / 20 °C / Inert atmosphere 3.1: iodine; samarium / tetrahydrofuran / 4 h / 60 °C / Inert atmosphere; Schlenk technique

Reference： [1]Huang, Fei; Zhang, Songlin [Organic Letters, 2019, vol. 21, # 18, p. 7430 - 7434]

80
[ 5162-44-7 ]
[ 122334-37-6 ]
[ 35204-91-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-4-butene With magnesium In tetrahydrofuran for 2h; Inert atmosphere; Reflux; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran at -10 - 20℃; Inert atmosphere;
	Stage #1: 1-bromo-4-butene With iodine; magnesium In diethyl ether for 0.5h; Inert atmosphere; Reflux; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; diethyl ether at -20 - 20℃; for 2h;

Reference： [1]Huang, Fei; Zhang, Songlin [Organic Letters, 2019, vol. 21, # 18, p. 7430 - 7434]
[2]Denisenko, Aleksandr; Garbuz, Pavel; Mykhailiuk, Pavel K.; Shishkina, Svetlana V.; Voloshchuk, Nataliya M. [Angewandte Chemie - International Edition, 2020, vol. 59, # 46, p. 20515 - 20521][Angew. Chem., 2020, vol. 132, # 46, p. 20696 - 20702,7]

81
1-((5-phenylpent-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide [ No CAS ]
[ 122334-37-6 ]
2-oxo-5-phenylpentyl 4-chlorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With water In dichloromethane at 80℃; for 8h;	11 Example 11 The reaction formula of this embodiment is as follows:Add 10a reaction flask to compound 1a (0.3mmol, 0.1561g).Compound 2e (3 mmol, 0.5989 g), water (1.5 μL), DCM (1.5 mL) dissolved the above materials, and the reaction was stirred at 80 ° C. for a reaction time of 8 h. After the reaction was completed, the solvent was spin-dried and evaporated to removeThe residue was subjected to flash column chromatography (PE: EA = 30: 1) to obtain pure 3ae (0.0760g)The yield was 80%.
80%	With water at 60℃; for 18h;

Reference： [1]Current Patent Assignee: XUZHOU MEDICAL UNIVERSITY - CN110668937, 2020, A Location in patent: Paragraph 0080-0083
[2]Wu, Nan; Li, Chuang; Mi, Jiajia; Zheng, Yan; Xu, Zhou [Organic Letters, 2020, vol. 22, # 18, p. 7118 - 7122]

82
[ 589-87-7 ]
[ 122334-37-6 ]
[ 27428-57-5 ]

Yield	Reaction Conditions	Operation in experiment
20.7 mg	Stage #1: 1,4-bromoiodobenzene With TurboGrignard In tetrahydrofuran at -20℃; for 3h; Schlenk technique; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; toluene at 23℃; Schlenk technique; Inert atmosphere; chemoselective reaction;

Reference： [1]Li, Guangchen; Szostak, Michal [Organic and biomolecular chemistry, 2020, vol. 18, # 20, p. 3827 - 3831]

83
[ 57999-46-9 ]
[ 122334-37-6 ]
(4-chlorophenyl)(2-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.7%	Stage #1: 2-(tetrahydropyran-2-yloxy)phenyl bromide With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 20℃; for 17h; Inert atmosphere;

Reference： [1]Clarkson, Guy J.; Wills, Martin; Zheng, Ye [Organic Letters, 2020]

84
[ 6638-79-5 ]
[ 122334-37-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 20℃; for 13h; Inert atmosphere;

Reference： [1]Kondoh, Azusa; Tasato, Naoko; Aoki, Takuma; Terada, Masahiro [Organic Letters, 2020, vol. 22, # 13, p. 5170 - 5175]

85
[ 109-09-1 ]
[ 122334-37-6 ]
[ 108-18-9 ]
[ 42330-59-6 ]
(2E,4E)-2-(4-chlorobenzoyl)-5-(diisopropylamino)penta-2,4-dienenitrile [ No CAS ]
N-(hydroxymethyl)-4-chloro-N-methylbenzamide [ No CAS ]
[ 6873-44-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 21% 2: 9% 3: 6% 4: 3%	Stage #1: diisopropylamine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: 2-chloropyridine In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #3: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78 - 22℃; for 13h; Inert atmosphere;	Phenyl[1-cyano-4-(diisopropylamino)butadienyl]ketones; GeneralProcedure (Table 1) General procedure: To a solution of DIPA (586.1 mg, 817 L, 5.792 mmol) in THF (5.5 mL)was slowly added n-BuLi (1.6 M solution in n-hexane, 3.36 mL, 5.378mmol) at -78 °C and the reaction mixture was stirred for 1 h. Then 2-chloropyridine (1; 563.7 mg, 470 L, 4.965 mmol) was added dropwiseto the mixture at -78 °C and it was stirred for 30 min. A solution of the corresponding Weinreb amide 2 or 2a-f (683.4 mg, 4.137mmol) in THF (2 mL) was slowly added to the mixture at -78 °C and it was stirred for 1 h. Then the mixture was gradually warmed to 22 °Cand stirred for 12 h. After sat. aq NH4Cl was added to the mixture, it was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo.

Reference： [1]Gim, Hyo Jin; Jung, Michael E. [Synthesis, 2019, vol. 51, # 12, p. 2548 - 2552]

86
1-[(methoxymethyl)sulfanyl]-2-(trifluoromethyl)benzene [ No CAS ]
[ 122334-37-6 ]
1-(4-chlorophenyl)-2-methoxy-2-[2-(trifluoromethyl)phenyl]sulfanyl}ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 1-[(methoxymethyl)sulfanyl]-2-(trifluoromethyl)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 4-chloro-N-methoxy-N-methylbenzamide In tetrahydrofuran; hexane at -78℃; for 1h;

Reference： [1]Ielo, Laura; Pillari, Veronica; Miele, Margherita; Holzer, Wolfgang; Pace, Vittorio [Advanced Synthesis and Catalysis, 2020, vol. 362, # 23, p. 5444 - 5449]

87
[ 4548-78-1 ]
[ 122334-37-6 ]
[ 236418-01-2 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;

Reference： [1]Chen, Ying-Chun; Du, Fei; Jiang, Kun; Liang, Wu; Ouyang, Qin; Shuai, Li; Wei, Ye; Yang, Jie [Angewandte Chemie - International Edition, 2020, vol. 59, # 43, p. 19222 - 19228][Angew. Chem., 2020, vol. 132, # 43, p. 19384 - 19390,7]

88
[ 122334-37-6 ]
C₁₂H₁₆ClNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 12 h / 0 - 20 °C / Inert atmosphere 2: hydroxylamine hydrochloride; sodium acetate; pyridine / ethanol; water / 20 °C

Reference： [1]Chen, Ying-Chun; Du, Fei; Jiang, Kun; Liang, Wu; Ouyang, Qin; Shuai, Li; Wei, Ye; Yang, Jie [Angewandte Chemie - International Edition, 2020, vol. 59, # 43, p. 19222 - 19228][Angew. Chem., 2020, vol. 132, # 43, p. 19384 - 19390,7]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	122334-37-6	MDL No. :	MFCD02684308
Formula :	C₉H₁₀ClNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LHUOAIXJPPMULP-UHFFFAOYSA-N
M.W :	199.63	Pubchem ID :	11275663
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.43
TPSA :	29.54 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.06 cm/s

Log Po/w (iLOGP) :	2.41
Log Po/w (XLOGP3) :	2.06
Log Po/w (WLOGP) :	1.97
Log Po/w (MLOGP) :	2.35
Log Po/w (SILICOS-IT) :	1.45
Consensus Log Po/w :	2.05

[ CAS No. 122334-37-6 ] {[proInfo.proName]}

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[ 122334-37-6 ] Synthesis Path-Upstream 1~1

[ 122334-37-6 ] Synthesis Path-Downstream 1~88

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[ 122334-37-6 ]

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

Log S (ESOL) :	-2.52
Solubility :	0.604 mg/ml ; 0.00303 mol/l
Class :	Soluble
Log S (Ali) :	-2.31
Solubility :	0.98 mg/ml ; 0.00491 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.82
Solubility :	0.304 mg/ml ; 0.00152 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.52

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

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 122334-37-6 ] {[proInfo.proName]}

Quality Control of [ 122334-37-6 ]

Related Doc. of [ 122334-37-6 ]

Product Details of [ 122334-37-6 ]

Calculated chemistry of [ 122334-37-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 122334-37-6 ]

Application In Synthesis of [ 122334-37-6 ]

[ 122334-37-6 ] Synthesis Path-Upstream 1~1

[ 122334-37-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 122334-37-6 ]

Aryls

Chlorides

Amides

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 122334-37-6 ]