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2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-6,8-dichloro-4H-3,1-benzoxazin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 3; Preparation of 3-bromo-1- (2-chlorophenyl)-N-[2,4-dichloro carbonyl]phenyl]-1H-pyrazol-5-carboxamide; Step A: Preparation of 2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-6,8-dichloro- 4H-3, 1 -benzoxazin-4-one; To a mixture of 3-bromo-1-(2-chlorophenyl)-lH-pyrazole-5-carboxylic acid (i. e. the carboxylic acid product of Example 1, Step E) (3.0 g, 9.44 mmol) and 3,5-dichloroanthranilic acid (1.94 g, 9.44 mmol) in acetonitrile (60 mL) was added 3-picoline (4.81 mL, 49.1 mmol) at room temperature, and the reaction mixture was stirred for 5 minutes. The reaction mixture was cooled to -10 C and methanesulfonyl chloride (1.91 mL, 24.56 mmol) in acetonitrile (5 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The resulting solids were isolated by filtration, washed with water, then dissolved in excess methylene chloride and dried (MgS04). The solvent was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel to afford the title compound (2.0 g). ¹H NMR (CDC13) No. 8.0 (s, 1H), 7.72 (s, 1H), 7.4-7.55 (m, 4H), 7.28 (s, 1H)
Step E: Preparation of 3-bromo-1- (2-chlorophenyl)-1H-pyrazole-5-carboxylic; Into a 100 mL flask containing the ester from Step D (5.8 g, 18.4 mmol) in methanol (40 mL) was added 12% aqueous sodium hydroxide (8.8 g, 30.5 mmol). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was then diluted with water (100 mL) and washed with diethyl ether (2 x 75 mL). The aqueous solution was acidified with concentrated hydrochloric acid to pH 2 and then extracted with ethyl acetate (3 x 150 mL). The combined ethyl acetate extracts were dried (MgS04) and concentrated under reduced pressure to afford the title compound (5.8 g). ¹H NMR (CDC13) No. 7.4-7.55 (m, 4H), 7.1 (s, 1H).
5.8 g
Step E: Preparation of 3-bromo-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid To a solution of methyl 3-bromo-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylate (i.e. the product from Step D) (5.8 g, 18.4 mmol) in methanol (40 mL) was added 12% aqueous sodium hydroxide (8.8 g, 30.5 mmol). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was then diluted with water (100 mL) and washed with diethyl ether (2 x 75 mL). The aqueous solution was acidified with concentrated hydrochloric acid to pH 2 and then extracted with ethyl acetate (3 x 150 mL). The combined ethyl acetate extracts were dried (MgSO4) and concentrated under reduced pressure to afford the title compound (5.8 g). 1H NMR (CDCl3) delta 7.4-7.55 (m, 4H), 7.1 (s, 1H).
2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-8-methyl-4-oxo-4H-3,1-benzoxazine-6-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Step H: Preparation of 2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-8-methyl-4- oxo-4H-3,1-benzoxazine-6-carbonitrile; To a solution of 3-bromo-1- (2-chlorophenyl)-1H-pyrazole-5-carboxylic (i. e. the carboxylic acid product of Step E) (2.0 g, 6.29 mmol) and 2-amino-3-methyl-5- cyanobenzoic acid (i. e. the product of Step G) (1.1 g, 6.29 mmol) in acetonitrile (60 mL) at room temperature was added 3-picoline (3.2 mL, 32.7 mmol). The reaction mixture was stirred for 5 minutes and then cooled to-10 C. Methanesulfonyl chloride (1.3 mL, 16.4 mmol) was then added dropwise, and after completion of the addition the reaction mixture was warmed to room temperature. On stirring overnight at room temperature, the reaction mixture formed a solid precipitate. The solid was isolated by filtration, washed with water, dissolved in excess methylene chloride and dried (MgS04). After removal of solvent, the residue was purified by chromatography on silica gel to afford the title compound (1.9 g). ¹H NMR (CDCI3) No. 8.31 (s, 1 H), 7.73 (s,lH), 7.45-7.6 (m, 4H), 7.31 (s,lH), 1.84 (s,lH).
With 3-Methylpyridine; methanesulfonyl chloride; In acetonitrile; at -10 - 20℃;
Step F: Preparation of 2-[3-bromo-1-(2-chlorophenyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one 3-Bromo-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid (i.e. the product from Step E) (0.165 g, 0.55 mmol), 2-amino-3-methyl-5-chlorobenzoic acid (0.101 g, 0.55 mmol) and 3-picoline (0.277 mL, 2.8 mmol) were combined with acetonitrile (10 mL) and cooled to -10 C. A solution of methanesulfonyl chloride (0.11 mL, 1.4 mmol) in acetonitrile (5 mL) was then added dropwise, and the reaction mixture was stirred at ambient temperature overnight. Water (10 mL) was added dropwise to the mixture to precipitate a solid. The solid was collected by filtration, washed successively with water and hexane, and then dried under nitrogen to afford the title compound as a white solid (0.216 g). 1H NMR (DMSO-d6) delta 7.90 (d, 1H), 7.73 (m, 2H), 7.6 (m, 3H), 7.48 (s, 1H), 1.73 (s, 3H).
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