反应详情

温度

102 °C

A solution of 1-(4-(5-bromo-1-ethylindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (Example 71, 35 mg, 0.042 mmol), L-(−)-proline (5 mg, 0.042 mmol), K2CO3 (12 mg, 0.084 mmol) and CuI (4 mg, 0.021 mmol) in DMSO (1.5 mL) was purged with air for 1 min. The resulting mixture was heated at 102° C. open to air for 20 h. The reaction mixture was then diluted with 1N aq. HCl solution and EtOAc. The organic layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (6 mg, 16%) as a white solid after lyophilization. 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.24 (dd, J=8.3, 1.9 Hz, 1H), 8.13-8.10 (m, 1H), 7.60-7.50 (m, 1H), 7.48 (s, 1H), 7.25-7.09 (m, 3.5H), 6.95 (s, 1H), 6.93 (d, J=7.5 Hz, 0.5H), 4.90-4.50 (m, 2H), 4.20-3.99 (m, 4H), 3.71-3.60 (m, 4H), 3.55-3.49 (m, 2H), 3.26-3.20 (m, 4H), 3.09-3.03 (m, 2H), 2.90-2.60 (m, 4H), 2.33 (s, 2H), 2.28 (s, 1H), 1.55-1.00 (m, 13H), 0.95-0.88 (m, 3H), 0.79-0.75 (m, 2H), 0.72-0.68 (m, 1H); MS(ESI+) m/z 844.5 (M+H)+.

1. customThe organic layer was separated
2. dry with materialdried over MgSO4
3. concentrationconcentrated in vacuo
4. customThe residue was purified by preparative HPLC