N-乙酰基-4-溴-3,5-二甲基苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Benzyltrimethylammonium tribromide (BTMA-Br3) (7.8 g, 20.21 mmol) was added to a solution of N-(3,5-dimethyl-phenyl)-acetamide (3.0 g, 18.38 mmol) in CH2Cl2/MeOH (90 ml/90 ml) at room temperature in an Ar atmosphere. The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and CH2Cl2 was then added to the resulting residue. The organic layer was washed with H2O, and then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=1:1) to give N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (4.0 g, yield 90%). The reaction mixture was concentrated under reduced pressure, and CH2Cl2 was then added to the resulting residue The organic layer was washed with H2O dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:EtOAc=1:1)

反应条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (100.0 mg, 0.307 mmol), N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (112. mg, 0.461 mmol), palladium(II) acetate (10 mg, 0.0461 mmol), tris(o-tolyl)phosphine (28 mg, 0.0922 mmol), triethylamine (0.128 ml, 0.922 mmol) and DMA (1.5 ml) was added to a sealed test tube in an N2 atmosphere. This mixture was heated with stirring at 130° C. for 13.5 hours. Palladium(II) acetate (10 mg, 0.0461 mmol), tris(o-tolyl)phosphine (28 mg, 0.0922 mmol) and triethylamine (0.128 ml, 0.922 mmol) were further added to the reaction mixture at room temperature in an N2 atmosphere, and the mixture was heated with stirring at 130° C. for 14 hours. The reaction mixture was cooled and water was then added. The aqueous layer was extracted with ethyl acetate (×3). The organic layers were combined and sequentially washed with water (×2) and saturated brine, and then dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH) to give N-{4-[(E)-2-(2-cyclohexyl-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl)-vinyl]-3,5-dimethyl-phenyl}-acetamide (61.4 mg, 41%). This mixture was heated the mixture was heated with stirring at 130° C. for 14 hours The reaction mixture was cooled The aqueous layer was extracted with ethyl acetate (×3) sequentially washed with water (×2) and saturated brine dried over sodium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (150 mg) in THF (5 mL) was added n-BuLi (1.36 mL, 1.0 M solution in hexane) at −78° C. The mixture was stirred at −78° C. for 30 min, then warmed up to −40° C. for 5 min, then cooled down to at −78° C. again. After 20 min, DMF (0.24 mL) was added. The mixture was stirred at −78° C. for 30 min and then allowed to warm up to room temperature for 1 h. The reaction was quenched with saturated NH4Cl aqueous solution and extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give N-(4-formyl-3,5-dimethyl-phenyl)-acetamide: MS (m/z) 192 (M+1). warmed up to −40° C. for 5 min cooled down to at −78° C. again After 20 min The mixture was stirred at −78° C. for 30 min to warm up to room temperature for 1 h The reaction was quenched with saturated NH4Cl aqueous solution extracted with EtOAc The organic extracts were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-3,5-dimethyl-phenylamine (130 mg) in CH2Cl2 (4 mL) was added acetic anhydride (0.123 mL) at 0° C. The mixture was allowed to warm up to room temperature and stirred for 2 h. The mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, EtOAc:Hexane=10:90 to 60:40) to give N-(4-bromo-3,5-dimethyl-phenyl)-acetamide: MS (m/z) 244 (M+1); 1H NMR (CDCl3, 400 MHz) δ 7.24 (s, 2H), 2.35 (s, 6H), 2.13 (s, 3H). The mixture was concentrated under reduced pressure The crude product was purified by column chromatography (SiO2, EtOAc:Hexane=10:90 to 60:40)