Reaction #72783

Reaction equation

water

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

K2CO3

1-(bromomethyl)-2-fluoro-3-methylbenzene

→

desired product

Yield 48.0%

methyl 1-[(2-fluoro-3-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate

Yield 48.0%

Solvents

DMF

Conditions

Workup

1. 1
   Otherprepared
2. 2
   TemperatureThe reaction mixture was cooled
3. 3
   Extractionextracted with EtOAc (50 mL×3)
4. 4
   DryingThe combined organic layers were dried over Na2SO4
5. 5
   Concentrationconcentrated
6. 6
   OtherThe resulting residue was purified by silica gel chromatography
7. 7
   Washeluted with EtOAc

Procedure

A mixture of methyl 2-methyl-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate prepared as described in Example 26, step d (500 mg, 1.82 mmol), K2CO3 (502 mg, 3.64 mmol) and 1-(bromomethyl)-2-fluoro-3-methylbenzene (389 mg, 1.91 mmol) in DMF (25 mL) was stirred at 80° C. for 18 h. The reaction mixture was cooled, poured into water (100 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel chromatography eluted with EtOAc:MeOH=100:1 to give the desired product (350 mg, 48%) as a red solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.24 (d, 3H, J=1.8 Hz), 2.47 (s, 3H), 3.09 (t, 4H, J=4.8 Hz), 3.75 (t, 4H, J=4.8 Hz), 3.86 (s, 3H), 5.51 (s, 2H), 6.62 (t, 1H, J=7.5 Hz), 7.00 (t, 1H, J=7.5 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.32 (d, 1H, J=2.4 Hz), 7.36 (d, 1H, J=2.4 Hz); LC-MS: m/e=398 [M+1]+

Source