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

HRID 1481230노트

반응식

HRID 1481230 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:15][C:16]([C:18]1[N:19]=[C:20]([C:37]#[N:38])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:22]=2)=O.C1CCN2C(=NCCC2)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:16]([C:18]1[N:19]=[C:20]([C:37]#[N:38])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:22]=2)=[O:15])([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 898130491-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester

생성물 1

HCID 898129723-{[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl ester수율 45.9%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
150 °C

실험 절차

A mixture of 3-amino-2-cyclopropyl-propionic acid tert-butyl ester (20 mg), 1-cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (15 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+: 492 (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-ce9d785fbbd84f2aa9de6a35fcaf4c49
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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