Potassium Carbonate → tert-butyl 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-ylcarbamate

HRID 450203Notes

Reaction equation

[F:1][CH:2]([F:22])[C:3]1[NH:7][C:6]2[CH:8]=[C:9]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:10]=[C:11]([O:12][CH3:13])[C:5]=2[N:4]=1.Cl[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH:27]=[C:26]([Cl:36])[N:25]=1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl.CCOC(C)=O>CN(C=O)C.O>[Cl:36][C:26]1[CH:27]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[N:29]=[C:24]([N:7]2[C:6]3[CH:8]=[C:9]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[CH:10]=[C:11]([O:12][CH3:13])[C:5]=3[N:4]=[C:3]2[CH:2]([F:1])[F:22])[N:25]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl 2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate (Example 64) (3.13 g, 10 mmol), 4-(2,6-dichloro-4-pyrimidinyl)morpholine (2.64 g, 11 mmol), and powdered K2CO3 (5 g, 40 mmol) in 30 mL DMF was heated at 100° C. for 8 hrs. The mixture was cooled and diluted with water to give a precipitate which was collected and dried. Chromatography on silica eluting with CH2Cl2/EtOAc (19:1) gave tert-butyl 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-ylcarbamate (2.49 g, 44% yield): mp (i-Pr2O) 233-236° C.; 1H NMR (CDCl3) δ 8.30 (s, 1H), 7.57 (t, JHF=53.8 Hz, 1H), 6.64 (m, 1H), 6.63 (d, J=1.8 Hz, 1H), 6.43 (s, 1H), 4.01 (s, 3H), 3.88-3.85 (m, 4H), 3.82-3.77 (m, 4H), 1.52 (s, 9H); Anal. Calcd. for C22H25ClF2N6O4: C, 51.7; H, 4.9; N, 16.45. Found: C, 52.0; H, 4.9; N, 16.6%.

Workup

temperatureThe mixture was cooled
customto give a precipitate which
customwas collected
customdried

Sources & evidence

ORD record: ord-ca83026a60184330939b5a7925b4fac5
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486939B2

Reaction notes

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