Sodium Iodide → N2-{4-[4-amino-1-(2-morpholinoethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

HRID 897835ノート

反応式

HRID 897835 の反応式
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.C(N(CC)CC)C.[I-].[Na+].[NH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1>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:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]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

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 8083Morpholine2 回HCID 8471TriethylamineHCID 223468312-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate2 回

生成物 1

HCID 22347049N2-{4-[4-amino-1-(2-morpholinoethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide収率 14.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To 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) (0.200 g, 0.373 mmol), triethylamine (0.052 mL, 0.37 mmol), and sodium iodide (0.056 g, 0.37 mmol) in DMF (5 mL) was added morpholine (0.039 mL, 0.45 mmol). The reaction mixture was heated at 60° C. for 60 h. Morpholine (0.100 mL, 1.15 mmol) was added and the reaction mixture was heated at 80° C. for 30 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. Water (5 mL) was added and the resulting precipitate was collected by filtration, washed with water (5 mL) and ether (10 mL), and dried in vacuo to afford a tan solid which was purified twice by silica gel chromatography (elution with 20% MeOH—CH2Cl2); the appropriate fractions were combined and concentrated to afford a beige solid which was triturated from ether and dried in vacuo to afford N2-{4-[4-amino-1-(2-morpholinoethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide as a white solid (0.048 g, 0.054 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.26 (1H, s), 8.11 (1H, d, J=8.0 Hz), 7.70 (1H, d, J=7.6 Hz), 7.58 (1H, d, J=7.6 Hz), 7.29-7.35 (4H, m), 7.15 (1H, t, J=7.6 Hz), 4.48 (2H, t, J=6.4 Hz), 4.04 (3H, s), 3.96 (3H, s), 3.50-3.53 (4H, m), 2.82 (2H, t, J=6.2 Hz), and 2.47-2.51 (4H, 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 10.02 min. MS: M+ 527.3.

後処理

  1. temperaturethe reaction mixture was heated at 80° C. for 30 h
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. concentrationconcentrated in vacuo
  4. additionWater (5 mL) was added
  5. filtrationthe resulting precipitate was collected by filtration
  6. washwashed with water (5 mL) and ether (10 mL)
  7. customdried in vacuo
  8. customto afford a tan solid which
  9. customwas purified twice by silica gel chromatography (elution with 20% MeOH—CH2Cl2)
  10. concentrationconcentrated
  11. customto afford a beige solid which
  12. customwas triturated from ether
  13. customdried in vacuo

出典と根拠

ORDレコード
ord-2a2cc37e167248d7bb0f86609a61f8d6
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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