1,2-Dichloroethane → (S)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-(dimethylamino)acetate

HRID 1517824ノート

反応式

HRID 1517824 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:22]([C:24]2[C:25](=[O:40])[N:26]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:27]([CH2:30][CH:31]([OH:33])[CH3:32])[C:28]=2[CH3:29])=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[CH3:41][N:42]([CH3:47])[CH2:43][C:44](O)=[O:45].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:41][N:42]([CH3:47])[CH2:43][C:44]([O:33][C@@H:31]([CH3:32])[CH2:30][N:27]1[C:28]([CH3:29])=[C:24]([C:22](=[O:23])[NH:21][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=4)[N:12]=[CH:11][CH:10]=3)=[C:2]([F:1])[CH:3]=2)[C:25](=[O:40])[N:26]1[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:45]

参加物

6

反応物 3

HCID 111,2-DichloroethaneHCID 673N,N-DimethylglycineHCID 595983963-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

生成物 1

HCID 59491008(S)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-(dimethylamino)acetate収率 61.7%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a mixture of (S)—N-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydro-xylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (0.54 g, 1 mmol), N,N-dimethylglycine (0.206 g, 2 mmol, Alfa) and DMAP (0.244 g, 2 mmol, Aladdin) in 15 mL of CH2Cl2 at 0° C. was added EDC solid (0.575 g, 3 mmol, Aladdin) in portions. The mixture was continued to stir at 0° C. for 2 hrs, then the reaction mixture was warmed up to room temperature and stirred at rt for 20 hrs. The reaction mixture was diluted with 100 mL of CH2Cl2 and washed with 0.1 N HCl (10 mL×2), followed by saturated NaHCO3 (20 mL×2) and water (20 mL×8), and the aqueous phase was extracted with EtOAc(15 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to afford the title compound as a yellow solid (0.387 g, 61.6%).

後処理

  1. temperaturethe reaction mixture was warmed up to room temperature
  2. stirringstirred at rt for 20 hrs
  3. washwashed with 0.1 N HCl (10 mL×2)
  4. extractionthe aqueous phase was extracted with EtOAc(15 mL×2)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc)

出典と根拠

ORDレコード
ord-8b727616d1764a9a8a0708bfa5201f2b
出典データセット
uspto-grants-2012_07
特許番号
US08232294B2

反応ノート

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