反应详情

温度

50 °C

To a solution of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid (Comp. No. 7c) (75 mg, 0.270 mmol) in dimethylformamide (2 ml) was added 1-hydroxybenzotriazole (41 mg, 0.30 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (58 mg, 0.30 mmol). The mixture was stirred for 2 h at 50° C., then 4-((R)-1-amino-propyl)-2-chloro-benzonitrile hydrochloride (68 mg, 0.3 mmol) and triethylamine (60 mg, 0.6 mmol) were added and the mixture was stirred at 25° C. overnight. The mixture was filtered through a small filter cartridge and the solution was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid) to give 82 mg (67%) of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(3-chloro-4-cyano-phenyl)-propyl]-amide as white solid. LC/MS (method 2): Rt=1.24 min; m/z=455.08 (M+H+). 1H-NMR: δ (ppm)=8.20 (1H, d), 7.94 (1H, d), 7.70 (1H, s), 7.50 (1H, d), 7.24 (1H, s), 4.95 (1H, d), 4.82-4.92 (2H, m), 4.20-4.29 (2H, m), 3.70-4.00 (5H, m), 2.07 (1H, m), 1.97 (1H, m), 1.74-1.85 (3H, m), 1.57 (1H, m), 1.19 (3H, d), 0.89 (3H, t).

1. stirringthe mixture was stirred at 25° C. overnight
2. filtrationThe mixture was filtered through a small filter cartridge
3. customthe solution was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid)