反应详情

Propyl [(7R)-7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate (2.5 g) and TEA (1.4 mL) were dissolved in 87 mL MeOH. Boc2O (2.1 g) was added in 10 mL MeOH, and the mixture was stirred for 2 h. The solvent was removed and propyl {(7R)-7-[(tert-butoxycarbonyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate was purified on silica gel (ethyl acetate/hexanes). Propyl {(7R)-7-[(tert-butoxycarbonyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate (3.15 g) was dissolved in DMF (81 mL). The mixture was cooled in an ice bath and MeI (3.47 g) was added followed by NaH (342 mg, 60% w/w in mineral oil). The ice bath was removed after 0.5 h, and the mixture was stirred for 1 h at RT. The reaction was quenched with ½ (sat.) aqueous ammonium chloride. Work up consisted of extraction of the aqueous layer with ether (2×). The combined organic fractions were washed with water and brine, then dried (MgSO4). The solvent was evaporated under reduced pressure and propyl {(7R)-7-[(tert-butoxycarbonyl)(methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate was purified on silica gel (ethyl acetate/hexanes). {(7R)-7-[(tert-butoxycarbonyl)-(methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate and anisole (2.2 g) were dissolved in 66 mL DCM. 66 mL of TFA was added and the mixture was stirred for 1 h. The mixture was then stripped several times with toluene. Work up consisted of extraction with dichloromethane (3×) from aqueous sodium carbonate. The combined organic fractions were washed with brine and dried (MgSO4). The solvent was evaporated under reduced pressure and propyl [(7R)-7-(methylamino)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate was obtained after purification on silica gel. (MeOH/DCM).

1. customThe solvent was removed
2. custompropyl {(7R)-7-[(tert-butoxycarbonyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate was purified on silica gel (ethyl acetate/hexanes)
3. dissolutionPropyl {(7R)-7-[(tert-butoxycarbonyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate (3.15 g) was dissolved in DMF (81 mL)
4. temperatureThe mixture was cooled in an ice bath
5. additionMeI (3.47 g) was added
6. customThe ice bath was removed after 0.5 h
7. stirringthe mixture was stirred for 1 h at RT
8. customThe reaction was quenched with ½ (sat.) aqueous ammonium chloride
9. extractionWork up consisted of extraction of the aqueous layer with ether (2×)
10. washThe combined organic fractions were washed with water and brine
11. dry with materialdried (MgSO4)
12. customThe solvent was evaporated under reduced pressure and propyl {(7R)-7-[(tert-butoxycarbonyl)(methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate
13. customwas purified on silica gel (ethyl acetate/hexanes)
14. dissolution{(7R)-7-[(tert-butoxycarbonyl)-(methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetate and anisole (2.2 g) were dissolved in 66 mL DCM
15. addition66 mL of TFA was added
16. stirringthe mixture was stirred for 1 h
17. extractionWork up consisted of extraction with dichloromethane (3×) from aqueous sodium carbonate
18. washThe combined organic fractions were washed with brine
19. dry with materialdried (MgSO4)
20. customThe solvent was evaporated under reduced pressure