Di-tert-butyl dicarbonate → propyl [(7R)-7-(methylamino)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate

HRID 476228

반응식

HRID 476228 반응식
[NH2:1][C@H:2]1[CH2:21][N:6]2[C:7]3[C:12]([C:13]([CH2:14][C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16])=[C:5]2[CH2:4][CH2:3]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[CH3:22]C(OC(OC(OC(C)(C)C)=O)=O)(C)C>CO>[CH3:22][NH:1][C@H:2]1[CH2:21][N:6]2[C:7]3[C:12]([C:13]([CH2:14][C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16])=[C:5]2[CH2:4][CH2:3]1)=[CH:11][CH:10]=[CH:9][CH:8]=3

참가 물질

4

반응물 2

HCID 90495Di-tert-butyl dicarbonateHCID 58349691(R)-propyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

생성물 1

HCID 86655417propyl [(7R)-7-(methylamino)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d076c1d93042422a80090660bcb310c7
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637671B2

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