Water → 5-(6,7-Dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline

HRID 871645

반응식

HRID 871645 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[C:9]([F:16])=[CH:10][C:11]([F:15])=[C:12]([OH:14])[CH:13]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH3:31])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.O>CN(C=O)C>[CH3:29][O:28][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][C:24]=1[O:30][CH3:31])[N:21]=[CH:20][N:19]=[C:18]2[O:14][C:12]1[C:11]([F:15])=[CH:10][C:9]([F:16])=[C:8]([CH:13]=1)[NH2:7]

참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 27829995-Amino-2,4-difluorophenol

생성물 1

HCID 668767545-(6,7-Dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a stirred suspension of cesium carbonate (3.25 g, 10.0 mmoles) in dry DMF (20 mL) was added 5-amino-2,4-difluorophenol (1.00 g, 6.9 mmoles). This solution was heated to 80° C. for 1 hour, and 4-chloro-6,7-dimethoxyquinazoline (1.59 g, 7.1 mmoles) was added and the reaction heated for an additional hour. At the end of this time the reaction was poured into water (200 mL) and extracted with two portions (200 mL) of ethyl acetate. The extracts were combined and dried over MgSO4. Filtration and concentration afforded 5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline as a crude red oil. Purification by silica gel chromatography eluting with an ethyl acetate/hexane gradient, 30%-70% over 70 minutes gave a slightly impure oil containing DMF. This oil was crystallized using ethyl acetate hexane to give a white solid.

후처리

  1. temperaturethe reaction heated for an additional hour
  2. extractionextracted with two portions (200 mL) of ethyl acetate
  3. dry with materialdried over MgSO4
  4. filtrationFiltration and concentration

출처 및 근거

ORD 기록
ord-641870b24ce9487baba2e59e125d8ed4
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969587B2

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