Potassium Carbonate → tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate

HRID 1256572노트

반응식

HRID 1256572 반응식
C([O-])([O-])=O.[K+].[K+].Cl[C:8]1[N:13]=[C:12]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[C:11]([N+:28]([O-:30])=[O:29])=[C:10]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[N:9]=1.[F:37][CH:38]([F:50])[C:39]1[NH:43][C:42]2[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:41]=2[N:40]=1>CN(C=O)C.O>[F:50][CH:38]([F:37])[C:39]1[N:43]([C:8]2[N:13]=[C:12]([NH:14][CH:15]3[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]3)[C:11]([N+:28]([O-:30])=[O:29])=[C:10]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)[N:9]=2)[C:42]2[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:41]=2[N:40]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 534881012-(Difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 86632675Tert-butyl 4-(2-chloro-6-morpholino-5-nitropyrimidin-4-ylamino)piperidine-1-carboxylate

생성물 1

HCID 66698145tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate수율 89%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

Powdered K2CO3 (1.305 g, 9.44 mmol) was added to a stirred suspension of tert-butyl 4-{[2-chloro-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate (U.S. Pat. Appl. Publ. No. 2009/0181963, the disclosure of which is incorporated herein by reference in its entirety) (1.047 g, 2.36 mmol) and 2-difluoromethyl-4-methoxy-1H-benzimidazole (Example 2) (608 mg, 3.07 mmol) in DMF (70 mL) at room temperature, and the mixture was stirred for 2.5 days. The reaction mixture was diluted with water, and the resulting precipitate was collected by filtration and dried. Recrystallization from CH2Cl2/MeOH gave tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate (1.27 g, 89%): mp 229-231° C.; 1H NMR (CDCl3) δ 8.64 (d, J=7.7 Hz, 1H), 7.81 (dd, J=8.4, 0.6 Hz, 1H), 7.36 (t, JHF=53.5 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.84 (d, J=7.7 Hz, 1H), 4.36 (m, 1H), 4.11 (m, 2H), 4.06 (s, 3H), 3.85 (t, J=4.9 Hz, 4H), 3.65 (t, J=4.6 Hz, 4H), 3.01 (t, J=11.5 Hz, 2H), 2.08 (m, 2H), 1.64-1.51 (m, 2H), 1.48 (s, 9H); Anal. Calcd. for C27H34F2N8O6: C, 53.6; H, 5.7; N, 18.5. Found: C, 53.35; H, 5.7; N, 18.8%.

후처리

  1. customat room temperature
  2. filtrationthe resulting precipitate was collected by filtration
  3. customdried
  4. customRecrystallization from CH2Cl2/MeOH

출처 및 근거

ORD 기록
ord-a06573d00c2c459fbf191dea21183cd4
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461158B2

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