Trifluoroacetic acid → N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)-4-((R)-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide

Participants

Reaction Steps

Trifluoroacetic acid (1 mL) was added to a solution of tert-butyl 4-(N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)carbamoyl)piperazine-1-carboxylate (311 mg, 0.7 mmol) in DCM (5 mL). The mixture was stirred at room temperature for 3 hours, and then concentrated in vacuo. The residue was dissolved in n-butanol (2 mL). N,N-Diisopropylethylamine (0.5 mL, 3.6 mmol) was added followed by (R)-4-chloro-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidine (113 mg, 0.84 mmol). The reaction mixture was heated at 80° C. for 16 hours. The mixture was then diluted with H2O, and extracted with DCM (2×20 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by preparative HPLC to give N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)-4-((R)-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide (39.9 mg, 12%). MS (APCI+) [M+H]+ 471.3. 1H NMR (CDCl3, 400 MHz) δ□: 8.49 (s, 1H), 7.40-7.35 (m, 2H), 7.17-7.13 (m, 2H), 4.06-3.95 (m, 4H), 3.77-3.70 (m, 2H), 3.51-3.44 (m, 1H), 3.39-3.02 (m, 11H), 2.42-2.32 (m, 1H), 1.88-1.82 (m, 1H), 1.33 (t, J=7.2 Hz, 6H), 1.15 (d, J=6.8 Hz, 3H).

Provenance & Evidence