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 1481231노트

반응식

HRID 1481231 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
150 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-a5b893c0bb524ca58b7bb5ad00f3d664
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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