Trifluoroacetic acid → N-(4-chlorobenzyl)-N-(2-(diethylamino)ethyl)-4-((5R)-6,7-dihydro-7-hydroxy-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-chlorobenzyl)-N-(2-(diethylamino)ethyl)carbamoyl)piperazine-1-carboxylate (88 mg, 0.19 mmol) in DCM (1 mL). The mixture was stirred at room temperature for 3 hours, and then concentrated in vacuo. The residue was dissolved in n-butanol (1 mL). N,N-diisopropylethylamine (0.11 mL, 0.6 mmol) was added to the solution. Then, (5R)-4-chloro-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-7-ol (37 mg, 0.20 mmol) was added to the solution. The reaction mixture was heated at 80° C. for 16 hours. The mixture was then diluted with H2O (1 mL), and extracted with DCM (2×5 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by preparative HPLC to give N-(4-chlorobenzyl)-N-(2-(diethylamino)ethyl)-4-((5R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide (19.9 mg, 21%). MS (APCI+) [M+H]+ 501.3. 1H NMR (CDCl3, 400 MHz) 8.46 (s, 1 H), 7.34 (d, J=8.4 Hz, 4 H), 7.13 (d, J=8.4 Hz, 4 H), 5.50 (t, J=8 Hz, 1 H), 5.28 (dd, J=3.6, 8.4 Hz, 1 H), 4.45 (s, 4 H), 4.14-4.04 (m, 4 H), 3.94-3.81 (m, 4 H), 3.51-3.42 (m, 8 H), 3.20-3.00 (m, 16 H), 2.73-2.64 (m, 2 H), 2.40-2.20 (m, 4 H), 2.05-1.98 (m, 1H), 1.86-1.78 (m, 1 H), 1.33 (d, J=7.2 Hz, 3 Hz), 1.28 (t, J=7.2 Hz, 12 H), 1.21 (d, J=6.8 Hz, 3 Hz).

Provenance & Evidence