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

反応式

HRID 640001 の反応式
[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

参加物

6

反応物 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

生成物 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-carboxylate収率 65%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-125644f320df4bad9429967237e8d12c
出典データセット
uspto-grants-2010_04
特許番号
US07691867B2

関連ノート

読み込み中…