Potassium Carbonate → methyl 1-(2,3-dichlorobenzyl)-2-(difluoromethyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylate

HRID 2174820Notes

Reaction equation

[F:1][CH:2]([F:22])[C:3]1[NH:7][C:6]2[C:8]([C:18]([O:20][CH3:21])=[O:19])=[CH:9][C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[CH:11][C:5]=2[N:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[Cl:38]>CN(C=O)C>[Cl:38][C:32]1[C:33]([Cl:37])=[CH:34][CH:35]=[CH:36][C:31]=1[CH2:30][N:4]1[C:5]2[CH:11]=[C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH:9]=[C:8]([C:18]([O:20][CH3:21])=[O:19])[C:6]=2[N:7]=[C:3]1[CH:2]([F:1])[F:22]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of methyl 2-(difluoromethyl)-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate, prepared as described in Example 68 (1000 mg, 3.2 mmol), K2CO3 (884 mg, 6.4 mmol) and 1-(bromomethyl)-2,3-dichlorobenzene (926 mg, 3.8 mmol) in DMF (30 mL) was stirred at 70° C. for 18 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was poured into water (100 mL) and filtered, the filter cake was collected and purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the desired product (1.4 g, 93%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 3.16(s, 4H), 3.74 (s, 4H), 3.92 (s, 3H), 5.77 (s, 2H), 6.21 (d, 1H, J=7.5 Hz), 7.20-7.58 (m, 5H); LC-MS: m/e=470 [M+1]+

Workup

customprepared
temperatureThe reaction mixture was cooled to room temperature
filtrationfiltered
additionThe filtrate was poured into water (100 mL)
filtrationfiltered
customthe filter cake was collected
custompurified by silica gel chromatography
washeluted with petroleum ether

Sources & evidence

ORD record: ord-1a0ec0db30854ba2af3770e450e64295
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062003B2

Reaction notes

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