Acetic Acid → tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate

HRID 2204564노트

반응식

HRID 2204564 반응식
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]1[C:15]1[N:19]2[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1.[OH-].[Na+].CC(O)=O>O1CCOCC1>[C:15]1([CH:3]2[CH:2]([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 58009941tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

생성물 1

HCID 58009929tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate수율 93%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

To a solution of tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (19.0 g, 37.3 mmol) in 1,4-dioxane (100 mL) was added aqueous NaOH (1N, 74.6 mL, 74.6 mmol). The reaction was heated at about 60° C. for about 30 min and allowed to cool to ambient temperature followed by the addition of 10% aqueous AcOH (250 mL). The mixture was extracted with with EtOAc (2×250 mL) and the combined organic layers were washed with brine (200 mL), dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography (330 g) eluting with a gradient of 10-70% EtOAc in heptane to provide tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate (12.3 g, 93%) as a white foam: LC/MS (Table 2, Method a) Rt=1.96 min; MS m/z: 356 (M+H)+.

후처리

  1. temperatureto cool to ambient temperature
  2. extractionThe mixture was extracted with with EtOAc (2×250 mL)
  3. washthe combined organic layers were washed with brine (200 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified by silica gel chromatography (330 g)
  8. washeluting with a gradient of 10-70% EtOAc in heptane

출처 및 근거

ORD 기록
ord-9d61a6ddc4fd4d21b42aed11409303ba
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365579B2

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