2,2-Dimethyl-3-phenylpropanoyl chloride → HCID 178488225, 화합물

HRID 432400

반응식

HRID 432400 반응식
[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].[CH3:33][C:34]([CH3:45])([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:35](Cl)=[O:36]>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:35](=[O:36])[C:34]([CH3:33])([CH3:45])[CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

참가 물질

4

반응물 2

HCID 133072292,2-Dimethyl-3-phenylpropanoyl chlorideHCID 178488198HCID 178488198, 화합물

생성물 1

HCID 178488225HCID 178488225, 화합물수율 59%

시약·촉매·용매 1

HCID 1049Pyridine용매

반응 조건

온도
0 °C

실험 절차

A solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.250 g, 0.573 mmol) in pyridine (3 mL) at 0° C. was treated with 2,2-dimethyl-3-phenylpropanoyl chloride (0.304 g, 1.55 mmol). The reaction mixture was stirred for 10 min at 0° C. The ice bath was removed and the reaction mixture was stirred at room temperature for 5 h. Solvent was removed under reduced pressure to dryness. Dichloromethane (15 mL) and saturated sodium bicarbonate solution (5 mL) were added to the solid. The layers were separated using an Empore extraction cartridge. The organic solvent was removed under reduced pressure. The crude solid was purified by flash chromatography using 10% methanol in dichloromethane, then 15% (methanol with 5% ammonium hydroxide) in dichloromethane as eluent. The crude solid from the previous purification was recrystallized using ethyl acetate and heptane. The precipitate was filtered to give 0.201 g (59%) of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide. A hot solution of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide (0.201, 0.337 mmol) in ethyl acetate was treated with a hot solution of maleic acid (0.117 g, 1.011 mmol) in ethyl acetate. The precipitate was filtered under nitrogen, and dried under high vacuum to give 0.265 g of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide tri-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 8.46 (s, 1H), 8.241 (s, 1H), 8.107-8.086 (d, 1H, J=8.4 Hz), 7.248-7.183 (m, 7H), 6.170 (s, 6H), 4.697 (m, 1H), 3.883 (s, 3H), 2.931 (s, 3H), 2.9-2.75 (br, s, 4H), 2.671 (s, 3H), 2.104-1.990 (m, 7H), 1.588-1.5632 (m, 2H), 1.226 (s, 7H); 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 5.413 min (95%).

후처리

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 5 h
  3. customSolvent was removed under reduced pressure to dryness
  4. additionDichloromethane (15 mL) and saturated sodium bicarbonate solution (5 mL) were added to the solid
  5. customThe layers were separated
  6. extractionan Empore extraction cartridge
  7. customThe organic solvent was removed under reduced pressure
  8. customThe crude solid was purified by flash chromatography
  9. customThe crude solid from the previous purification
  10. customwas recrystallized
  11. filtrationThe precipitate was filtered

출처 및 근거

ORD 기록
ord-2b54cfa1d8f24dd88486786016ef4b9c
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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