(2S)-1-methoxycarbonylpyrrolidine-2-carboxylic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-(6-(aminomethyl)-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (70 mg, 0.11 mmol), (S)-1-(methoxycarbonyl)pyrrolidine-2-carboxylic acid (38 mg, 0.22 mmol), EDCI (12 mg, 0.27 mmol), DMAP (40 mg, 0.33 mmol) and triethylamine (33 mg, 0.33 mmol) in CH2Cl2 (2 mL) was stirred at room temperature overnight. The mixture was then purified using Prep-TLC(CH2Cl2:EtOAc=1:1) to provide (2S)-methyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate (60 mg, yield: 69.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.86˜8.05 (m, 3H), 7.28˜7.69 (m, 4H), 7.16˜7.27 (m, 5H), 6.85 (d, J=9.2 Hz, 1H), 6.60 (dd, J=5.2, 7.2 Hz, 1H), 5.98˜6.25 (m, 1H), 4.31 (br. s, 1H), 3.65 (br. s, 5H), 3.39 (s, 5H), 2.97 (d, J=3.2 Hz, 3H), 2.72 (br. s, 3H), 1.90˜2.49 (m, 2H), 1.63˜1.79 (m, 2H). MS (M+H)+: 799. The mixture was then purified