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 1894154ノート

反応式

HRID 1894154 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-b936bfd7631e4701b1226d1ae91833e7
出典データセット
uspto-grants-2013_08
特許番号
US08513271B2

反応ノート

読み込み中…