Potassium Carbonate → Methyl 3-(pyrrolidin-1-ylmethyl)benzoate

Methyl-3-(bromomethyl)benzoate (0.115 g, 0.5 mmol), pyrrolidine (0.036 g, 0.5 mmol) and K2CO3 (0.069 g, 0.5 mmol) were dissolved in DMF (2.5 ml) and stirred at reflux for 18 h. The reaction mixture was the reduced in vacuo and subject to column chromatography eluting with hexane ethyl acetate (1:1) to give the crude 3-pyrrolidin-1-ylmethyl-benzoic acid methyl ester, which was added to a solution of LiOH (0.014 g, 0.33 mmol) in 1:1 THF:H2O (1 ml). The reaction mixture was stirred at ambient temperature for 18 h, reduced in vacuo and dried through azeotrope with toluene (×3). The resulting solid was dissolved in water (1 ml), acidified with 2M HCl (1 ml), reduced in vacuo and dried through azeotrope with toluene (×3) to give a clear, pale yellow gel. This was combined with 3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-ylamine (0.050 g, 0.25 mmol), EDC (0.058 g, 0.30 mmol) and HOBt (0.041 g, 0.30 mmol) and the reaction mixture was stirred at ambient temperature in DMSO (0.75 ml) for 64 h. The reaction mixture was purified by preparative LC/MS to give the formate salt of N-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-3-pyrrolidin-1-ylmethyl-benzamide (0.018 g, 9% over 3 steps) as a buff coloured solid. (LC/MS: Rt 1.86, [M+H]+ 387.16).

1. temperatureat reflux for 18 h
2. washeluting with hexane ethyl acetate (1:1)

ORD record

ord-7fa02c1a336843e395050bcf298fff08

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977477B2