Water → tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate

HRID 640001

반응식

HRID 640001 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([OH:27])=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:40][CH:41]1[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42]1)(=O)=O.O>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH2:40][CH:41]5[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:50])([CH3:52])[CH3:51])=[O:47])[CH2:42]5)=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 4183641tert-Butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 136383490N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide

생성물 1

HCID 68638512tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate수율 65%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
80 °C

실험 절차

A mixture of N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide (0.59 g, 1.2 mmol), cesium carbonate (1.95 g, 6.0 mmol) and tert-butyl 3-{[(methylsulphonyl)oxy]methyl}pyrrolidine-1-carboxylate (assumed 1.3 mmol) in dimethyl acetamide (10 ml) was heated at 80° C. for 6 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulphate and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 4 to 7% methanol in dichloromethane to yield tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate (0.435 g, 65% yield): MS (+ve ESI): 562 (M+H)+.

후처리

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 4 to 7% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-125644f320df4bad9429967237e8d12c
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691867B2

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