1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-{[7-Cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl ester

HRID 1481231ノート

反応式

HRID 1481231 の反応式
[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH2:9])([CH3:4])([CH3:3])[CH3:2].C([O:16][C:17]([C:19]1[N:20]=[C:21](C#N)[C:22]2[C:27]([C:28]=1[OH:29])=[CH:26][CH:25]=[C:24]([O:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:32]=1[F:38])[CH:23]=2)=O)C.C1CCN2[C:44](=[N:45]CCC2)CC1>CC(N(C)C)=O>[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH:9][C:17]([C:19]1[N:20]=[CH:21][C:22]2[C:27]([C:28]=1[OH:29])=[CH:26][CH2:25][C:24]([C:44]#[N:45])([O:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:32]=1[F:38])[CH:23]=2)=[O:16])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89812868Tert-butyl 3-amino-2-cyclopropylpropanoateHCID 898129111-Cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

生成物 1

HCID 1178441063-{[7-Cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl ester収率 45.2%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
150 °C

実験手順

A mixture of 3-amino-2-cyclopropyl-propionic acid tert-butyl ester (20 mg), 1-cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (16 mg) and DBU (10 mg) in DMA (0.3 mL) was heated in an oil bath (150° C.) for 1 h. The reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulfate solution, filtered, concentrated and silica gel column purified to give desired product as brown solid (10 mg). LC-MS ESI+: 510 (M+1)+.

後処理

  1. customThe reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase
  2. customwas separated
  3. washwashed with water, diluted NaCl solution
  4. dry with materialdried over anhydrous sodium sulfate solution
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customsilica gel column purified

出典と根拠

ORDレコード
ord-a5b893c0bb524ca58b7bb5ad00f3d664
出典データセット
uspto-grants-2016_08
特許番号
US09409892B2

反応ノート

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