Diisopropylethylamine → (1R,6S)[8-(4,6-Dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]oct-3-yl]-(2-thiophen-2-yl-phenyl)-methanone

Participants

Reaction Steps

A mixture of (1R,6S)8-(4,6-dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]octane (Intermediate 4, 28 mg, 0.13 mmol), 2-thiophen-2-yl-benzoic acid (29 mg, 0.14 mmol), HATU (73.2 mg, 0.19 mmol), diisopropylethylamine (50 mg, 0.38 mmol) was stirred in DMF (4 mL) at room temperature for 2 h. Then the reaction mixture was partitioned between water and ethyl acetate mixture. The organic phase was separated and washed with 1N aq. NaOH (10 mL) and then with water (2×15 mL). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified on HPLC (basic system) to yield the title compound (31.0 mg, 59.8%). MS (ESI) mass calcd. for C23H24N4OS, 404.53; m/z found, 405.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.60-6.75 (m, 7H), 6.43-6.10 (m, 1H), 4.10-1.78 (m, 16H).

Provenance & Evidence