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 516413Notes

Reaction equation

HRID 516413 reaction equation
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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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%.

Workup

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

Sources & evidence

ORD record
ord-f264f57c362f42bbb02d7975cf5ac627
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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