Ammonia → (S)-Benzyl 2-(8-amino-1-bromoimidazo(1,5-a)pyrazin-3-yl)pyrrolidine-1-carboxylate

HRID 928295노트

반응식

HRID 928295 반응식
[Br:1][C:2]1[N:3]=[C:4]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[N:5]2[CH:10]=[CH:9][N:8]=[C:7](Cl)[C:6]=12.[NH3:27]>CC(O)C>[NH2:27][C:7]1[C:6]2[N:5]([C:4]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[N:3][C:2]=2[Br:1])[CH:10]=[CH:9][N:8]=1

참가 물질

4

반응물 2

HCID 222AmmoniaHCID 867203031-Pyrrolidinecarboxylic acid, 2-(1-bromo-8-chloroimidazo(1,5-a)pyrazin-3-yl)-, phenylmethyl ester, (2S)-

생성물 1

HCID 71233875(S)-Benzyl 2-(8-amino-1-bromoimidazo(1,5-a)pyrazin-3-yl)pyrrolidine-1-carboxylate수율 86%

시약·촉매·용매 1

HCID 3776Isopropanol용매2회

실험 절차

(S)-Benzyl 2-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (20.54 mmol, 8.95 g) was suspended in 2-propanol (113 ml) in a pressure vessel. 2-propanol (50 ml) was cooled to −78° C. in a pre-weighed flask (with stopper and stirring bar) and ammonia gas (646 mmol, 11 g) was led through for 15 minutes. The resulting solution was added to the suspension in the pressure vessel. The vessel was closed and stirred at room temperature and a slight increase in pressure was observed. Then the suspension was heated to 110° C. which resulted in an increased pressure to 4.5 bar. The clear solution was stirred at 110° C., 4.5 bar overnight. After 18 h the pressure remained 4 bar. The reaction mixture was concentrated in vacuum, the residue was suspended in ethyl acetate and subsequently washed with water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, saturated sodium chloride solution, dried over sodium sulfate and concentrated to give 7.35 g of (S)-benzyl 2-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (86%).

후처리

  1. customwas led through for 15 minutes
  2. additionThe resulting solution was added to the suspension in the pressure vessel
  3. customThe vessel was closed
  4. temperaturea slight increase in pressure
  5. temperatureThen the suspension was heated to 110° C. which
  6. customresulted in an increased pressure to 4.5 bar
  7. stirringThe clear solution was stirred at 110° C.
  8. custom4.5 bar overnight
  9. concentrationThe reaction mixture was concentrated in vacuum
  10. washsubsequently washed with water
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with ethyl acetate
  13. washThe combined organic layers were washed with water, saturated sodium chloride solution
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated

출처 및 근거

ORD 기록
ord-6675f56a73ea482cab981dd7ac1df8b5
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290504B2

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