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 1256573노트

반응식

HRID 1256573 반응식
[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

참가 물질

5

반응물 2

HCID 682631,1'-Carbonyldiimidazole2회HCID 66698145tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate

생성물 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-piperidinecarboxylate수율 69%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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%.

후처리

  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)

출처 및 근거

ORD 기록
ord-509b6ced631547e69600cd55d5b74f87
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461158B2

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