Acetyl chloride → 2-(S)-{[4-(3-Acetoxy-phenoxy)-2-(5-methoxy-pyridin-3-yl)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1894154노트

반응식

HRID 1894154 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)=[N:17][C:18]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([O:27][CH3:28])[CH:26]=2)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:37](Cl)(=[O:39])[CH3:38].C(N(CC)CC)C>O1CCCC1.CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37](=[O:39])[CH3:38])[CH:31]=2)=[N:17][C:18]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([O:27][CH3:28])[CH:26]=2)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 671955742-(S)-{[4-(3-Hydroxy-phenoxy)-2-(5-methoxy-pyridin-3-yl)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 671934892-(S)-{[4-(3-Acetoxy-phenoxy)-2-(5-methoxy-pyridin-3-yl)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester수율 80.3%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

To a solution of Compound 10a (50 mg; 0.1 mmol) in tetrahydrofuran (5 mL), cooled to −78° C., was added acetyl chloride (0.009 mL; 0.12 mmol) and triethylamine (0.035 mL; 0.25 mmol). The mixture was stirred at −78° C. for 1 hour. Diluted the resulted mixture with EtOAc and H2O. The organic phase was washed sequentially with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a EtOAc-heptane gradient to afford Compound 10b (43 mg; 80% yield). MS: m/z 536.0 (M+H)+.

후처리

  1. washThe organic phase was washed sequentially with H2O
  2. dry with materialdried over Na2SO4
  3. filtrationThe mixture was filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customto give the crude material
  6. customThe crude material was purified by flash column chromatography (SiO2)
  7. washeluting with a EtOAc-heptane gradient

출처 및 근거

ORD 기록
ord-b936bfd7631e4701b1226d1ae91833e7
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513271B2

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