Reaction #72785

Reaction equation

water

methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate

1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene

K2CO3

→

crude product

Yield 29.0%

methyl 2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

Yield 29.0%

Solvents

MeOH

DMF

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was cooled to rt
2. 2
   Extractionextracted with EtOAc (30 mL×3)
3. 3
   WashThe combined organic layers were washed with brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Concentrationconcentrated
6. 6
   OtherThe resulting residue was purified by silica gel chromatography
7. 7
   Washeluted with DCM

Procedure

A solution of methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate prepared as described in Example 26, step d (500 mg, 1.8 mmol), 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (483 mg, 1.9 mmol) and K2CO3 (497 mg, 3.6 mmol) in DMF (50 mL) was stirred at 80° C. for 3 h. The reaction mixture was cooled to rt and poured into water (50 mL), extracted with EtOAc (30 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel chromatography eluted with DCM:MeOH=50:1 to give the crude product (230 mg, yield 29%), as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.39 (s, 3H), 2.54 (s, 3H), 3.08 (t, 4H, J=4.8 Hz), 3.72 (t, 4H, J=4.8 Hz), 3.89 (s, 3H), 5.57 (s, 2H), 6.27 (d, 1H, J=7.5 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.27 (d, 1H, J=2.4 Hz), 7.38 (d, 1H, J=2.4 Hz) 7.60 (d, 1H, J=7.5 Hz); LC-MS: m/e=448 [M+1]+

Source