1,1'-Carbonyldiimidazole → Tert-butyl 4-[2-[2-(difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-8-oxo-7,8-dihydro-9h-purin-9-yl]-1-piperidinecarboxylate

HRID 1256573ノート

反応式

HRID 1256573 の反応式
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[F:13][CH:14]([F:55])[C:15]1[N:19]([C:20]2[N:25]=[C:24]([NH:26][CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[C:23]([N+:40]([O-])=O)=[C:22]([N:43]3[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)[N:21]=2)[C:18]2[CH:49]=[CH:50][CH:51]=[C:52]([O:53][CH3:54])[C:17]=2[N:16]=1>O1CCOCC1.O>[F:13][CH:14]([F:55])[C:15]1[N:19]([C:20]2[N:25]=[C:24]3[C:23]([NH:40][C:1](=[O:2])[N:26]3[CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)=[C:22]([N:43]3[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)[N:21]=2)[C:18]2[CH:49]=[CH:50][CH:51]=[C:52]([O:53][CH3:54])[C:17]=2[N:16]=1

参加物

5

反応物 2

HCID 682631,1'-Carbonyldiimidazole2 回HCID 66698145tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate

生成物 1

HCID 67544210Tert-butyl 4-[2-[2-(difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-8-oxo-7,8-dihydro-9h-purin-9-yl]-1-piperidinecarboxylate収率 69%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

1,1′-Carbonyldiimidazole (689 mg, 4.25 mmol) was added to a solution of the above amine (244 mg, 0.425 mmol) in 1,4-dioxane (25 mL) and the mixture was refluxed under nitrogen for 4.5 hrs. Additional 1,1′-carbonyldiimidazole (689 mg, 4.25 mmol) was added, and the mixture refluxed for additional 17.5 hrs. The mixture was cooled to room temperature and diluted with water. The resulting precipitate was collected by filtration, washed with H2O, and dried. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 97:3), gave tert-butyl 4-[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate (176 mg, 69%): mp (CH2Cl2/i-Pr2O) 269-272° C.; 1H NMR (CDCl3) δ 10.94 (br s, 1H), 7.73 (dd, J=8.3, 0.3 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.36 (t, JHF=53.6 Hz, 1H), 6.81 (d, J=7.8 Hz, 1H), 4.49 (tt, J=12.1, 4.1 Hz, 1H), 4.38 (br s, 2H), 4.06 (s, 3H), 3.89 (dd, J=5.6, 3.6 Hz, 4H), 3.82 (dd, J=5.6, 3.7 Hz, 4H), 2.85 (m, 2H), 2.56 (m, 2H), 1.83 (d, J=11.0 Hz, 2H), 1.48 (s, 9H); Anal. Calcd. for C28H34F2N8O5.0.1 i-Pr2O: C, 56.2; H, 5.8; N, 18.3. Found: C, 56.2; H, 5.90; N, 18.0%.

後処理

  1. temperaturethe mixture was refluxed under nitrogen for 4.5 hrs
  2. temperaturethe mixture refluxed for additional 17.5 hrs
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with H2O
  5. customdried
  6. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 97:3)

出典と根拠

ORDレコード
ord-509b6ced631547e69600cd55d5b74f87
出典データセット
uspto-grants-2013_06
特許番号
US08461158B2

反応ノート

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