Triethylamine → N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

HRID 897833노트

반응식

HRID 897833 반응식
CS(O[CH2:6][CH2:7][N:8]1[C:12]2=[N:13][CH:14]=[N:15][C:16]([NH2:17])=[C:11]2[C:10]([C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]3[N:28]([CH3:36])[C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])=[C:20]([O:37][CH3:38])[CH:19]=2)=[N:9]1)(=O)=O.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(N(CC)CC)C>CN(C=O)C>[NH2:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][CH2:6][N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]4[N:28]([CH3:36])[C:29]5[C:34]([CH:35]=4)=[CH:33][CH:32]=[CH:31][CH:30]=5)=[O:26])=[C:20]([O:37][CH3:38])[CH:19]=3)[C:11]=12

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 223468312-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate2회

생성물 1

HCID 22347346N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide수율 32.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

A mixture of 2-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate (Intermediate 4) (0.265 g, 0.495 mmol), N-methylpiperazine (0.065 mL, 0.58 mmol), and triethylamine (0.10 mL, 0.74 mmol) in DMF (5 mL) was heated at 70° C. for 20 h. The reaction mixture was cooled to ambient temperature and the solvent removed in vacuo. Water (25 mL) was added and the resulting precipitate was collected by filtration, washed with water (25 mL) and ether (50 mL), and dried in vacuo to afford a brown solid which was purified by silica gel column chromatography. The appropriate fractions were combined and concentrated to afford N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide as a beige solid (0.084 g, 0.16 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.26 (1H, s), 8.11 (1H, d, J=8.4 Hz), 7.70 (1H, d, J=8.4 Hz), 7.29-7.35 (4H, m), 7.15 (1H, t, J=7.4 Hz), 4.46 (2H, t, J=6.8 Hz), 4.04 (3H, s), 3.96 (3H, s), 2.80 (2H, t, J=6.6 Hz), 2.49-2.50 (2H, obscured by DMSO peak), 2.23-2.26 (4H, m), 2.12 (3H, s), and 0.97-0.99 (2H, m); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.24. MS: MH+ 540.3.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe solvent removed in vacuo
  3. additionWater (25 mL) was added
  4. filtrationthe resulting precipitate was collected by filtration
  5. washwashed with water (25 mL) and ether (50 mL)
  6. customdried in vacuo
  7. customto afford a brown solid which
  8. customwas purified by silica gel column chromatography
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e8dbff4d485d41619dec110c44ddbe66
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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