trans-2-Phenyl-1-cyclopropanecarbonyl chloride → HCID 178488229、化合物

HRID 432402

反応式

HRID 432402 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]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N: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].[C:33]1([C@@H:39]2[CH2:41][C@H:40]2[C:42](Cl)=[O:43])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>N1C=CC=CC=1>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:42]([C@H:40]4[CH2:41][C@@H:39]4[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:43])=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

参加物

4

反応物 2

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chloride2 回HCID 178488198HCID 178488198、化合物

生成物 1

HCID 178488229HCID 178488229、化合物収率 70%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
0 °C

実験手順

A solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.162 g, 0.371 mmol) in pyridine (2 mL) at 0° C. was treated with trans-2-phenyl-1-cyclopropylcarbonyl chloride (0.134 g, 0.742 mmol) under a nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0° C., the ice bath was removed and the reaction mixture stirred at room temperature for 5 h. Additional trans-2-phenyl-1-cyclopropylcarbonyl chloride (0.034 g, 0.186 mmol) was added and the reaction mixture stirred for 1 h. The organic layer was removed under reduced pressure, and dichloromethane (15 mL) was then added. The layers were separated using an Empore extraction cartridge. The organic layer was removed under reduced pressure. The crude product was purified by flash chromatography on silica gel using 15% methanol in dichloromethane then 20% methanol in dichloromethane as eluent. The column afforded 0.150 g (70%) of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide. A hot solution of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide (0.147, 0.253 mmol) in ethyl acetate was treated with a hot solution of maleic acid (0.088 g, 0.759 mmol) in ethyl acetate. The precipitate formed was filtered under nitrogen and dried under high vacuum to give 0.204 g of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide tris-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 9.64 (s, 1H), 8.23-8.21 (m, 2H), 7.33-7.29 (m, 2H), 7.24-7.17 (m, 4H), 6.16 (s, 6H), 4.69-4.66 (m, 1H), 3.90 (s, 3H), 2.90-2.60 (m, 7H), 2.37-2.35 (m, 2H), 2.10-1.99 (m, 8H), 1.70-1.50 (m, 3H), 1.32 (m, 1H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.346 min (97%).

後処理

  1. customthe ice bath was removed
  2. stirringthe reaction mixture stirred at room temperature for 5 h
  3. stirringthe reaction mixture stirred for 1 h
  4. customThe organic layer was removed under reduced pressure, and dichloromethane (15 mL)
  5. additionwas then added
  6. customThe layers were separated
  7. extractionan Empore extraction cartridge
  8. customThe organic layer was removed under reduced pressure
  9. customThe crude product was purified by flash chromatography on silica gel using 15% methanol in dichloromethane

出典と根拠

ORDレコード
ord-27ed9dc1e0784affab396cc89c99f7bf
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

関連ノート

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