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

HRID 928295ノート

反応式

HRID 928295 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒2 回

実験手順

(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%).

後処理

  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

出典と根拠

ORDレコード
ord-6675f56a73ea482cab981dd7ac1df8b5
出典データセット
uspto-grants-2016_03
特許番号
US09290504B2

反応ノート

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