反应详情

To a solution of 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoroindolin-5-yl)cyclopropanecarboxamide (160 mg, 0.50 mmol) in anhydrous dichloromethane (3.4 mL) was added 3-(benzyloxy)propanal (160 mg, 0.98 mmol) at room temperature. After 10 min of stirring, NaBH(OAc)3(140 mg, 0.65 mmol) was added in one portion and the reaction mixture was stirred for 4 h at room temperature. The solvent was removed under reduced pressure and the residue was taken-up in a mixture of 50/50 CH3CN—H2O containing 0.05% TFA, The mixture was concentrated to dryness and the residue was dissolved in CDCl3(5 mL) and briefly exposed to daylight. The purple solution was stirred open to the atmosphere at room temperature for 2 h. The solvent was removed under reduced pressure and the residue was treated with Pd—C (10 mg) in MeOH (2 mL) under 1 atm of H2 2 h. The catalyst was filtered through Celite and the solvent was removed under reduced pressure. The residue was purified by preparative TLC 30% ethyl acetate/hexanes to provide 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoro-1-(3-hydroxypropyl)-1H-indol-5-yl)cyclopropanecarbox amide (18 mg, 8% from 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoroindolin-5-yl)cyclopropane-carboxamide). 1 H NMR (400 MHz, CDCl3) δ 8.11(d, J=7.8 Hz, 1H), 7.31(d, J=2.2 Hz, 1H), 6.94(dd, J=7.9, 1.7 Hz, 1H), 6.91(d, J=1.6 Hz, 1H), 6.85(d, J=11.7 Hz, 1H), 6.79(d, J=7.9 Hz, 1H), 6.10(s, 1H), 5.94(s, 2H), 4.25-4.21(m, 2H), 3.70(dd, J=5.7, 5.7 Hz, 2H), 1.93-1.86(m, 2H), 1.61(dd, J=6.8, 3.7 Hz, 2H), 1.35(s, 9H), 1.04(dd, J=6.8, 3.7 Hz, 2H). MS (ESI) m/e (M+H+) 453.0.

1. stirringthe reaction mixture was stirred for 4 h at room temperature
2. customThe solvent was removed under reduced pressure
3. additionthe residue was taken-up in a mixture of 50/50 CH3CN—H2O containing 0.05% TFA
4. concentrationThe mixture was concentrated to dryness
5. dissolutionthe residue was dissolved in CDCl3(5 mL)
6. stirringThe purple solution was stirred open to the atmosphere at room temperature for 2 h
7. customThe solvent was removed under reduced pressure
8. additionthe residue was treated with Pd—C (10 mg) in MeOH (2 mL) under 1 atm of H2 2 h
9. filtrationThe catalyst was filtered through Celite
10. customthe solvent was removed under reduced pressure
11. customThe residue was purified by preparative TLC 30% ethyl acetate/hexanes