4-(Trifluoromethoxy)benzoyl Chloride → N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide

HRID 432316ノート

反応式

HRID 432316 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].[F:33][C:34]([F:46])([F:45])[O:35][C:36]1[CH:41]=[CH:40][C:39]([C:42](Cl)=[O:43])=[CH:38][CH:37]=1>N1C=CC=CC=1.ClCCl>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:42](=[O:43])[C:39]4[CH:40]=[CH:41][C:36]([O:35][C:34]([F:33])([F:45])[F:46])=[CH:37][CH:38]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

参加物

5

反応物 2

HCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 223469753-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 22347199N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide収率 67%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
-5 °C

実験手順

A solution of 3-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.450 g, 1.03 mmol) in pyridine (8 mL) at −5° C. was treated with a solution of 4-(trifluoromethoxy)-1-benzenecarbonyl chloride (0.231 g, 1.03 mmol) in dichloromethane (2.5 mL) drop-wise. The reaction mixture was stirred at −5° C. for 30 min. The ice bath was removed and the reaction mixture was stirred at room temperature for 3 h. 1 N sodium hydroxide solution (10 mL) was added, and stirred for 1 h. The organic solvent was removed under reduced pressure. Dichloromethane (10 mL) was added and the layers were separated using an Empore extraction cartridge. The organic solvent was removed under reduced pressure and the crude compound was purified by flash chromatography on silica gel using 10% methanol in dichloromethane as eluent to give 0.430 g (67%) N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide. A hot solution of N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide (0.430 g, 0.688 mmol) in ethyl acetate (15 mL) was treated with a hot solution of maleic acid (0.240 g, 2.07 mmol) in ethyl acetate. A precipitate was formed, filtered under nitrogen, and dried under high vacuum to give N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide tris-maleate salt.

後処理

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 3 h
  3. addition1 N sodium hydroxide solution (10 mL) was added
  4. stirringstirred for 1 h
  5. customThe organic solvent was removed under reduced pressure
  6. additionDichloromethane (10 mL) was added
  7. customthe layers were separated
  8. extractionan Empore extraction cartridge
  9. customThe organic solvent was removed under reduced pressure
  10. customthe crude compound was purified by flash chromatography on silica gel using 10% methanol in dichloromethane as eluent

出典と根拠

ORDレコード
ord-df13437c83384d1b8f1a55570bb09be8
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

反応ノート

読み込み中…