Formamide → tert-butyl 4-(5-vinyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

関与物質

反応条件

反応手順

Ethyl 2-amino-5-vinylcyclopent-1-enecarboxylate (2.132 g, 12.75 mmol) was mixed with ammonium formate (4.02 g, 63.75 mmol) and formamide (5.56 mL, 127.5 mmol) and heated at 140° C. for 16 hours. The mixture was diluted with water (50 mL) and 20% IPA-DCM (100 mL). Solids were filtered off (Celite). The organic layer was separated. The aqueous layer was extracted with 20% IPA-DCM (3×50 mL). The combined organic solutions were washed with brine (20 mL) and dried (Na2SO4). After filtration and concentration, toluene (10 mL) was added to the crude (1.543 g), mixed, and evaporated. The resulting 5-vinyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one was mixed with acetonitrile (30 mL) and POCl3 (2.62 mL, 28.54 mmol) and heated at 80° C. for 20 hours. The mixture was cooled to 0° C. 50% KOH (11.25 mL, 142.7 mmol) was added dropwise. t-Butyl piperazine-1-carboxylate (5.31 g, 28.53 mmol) was added. The mixture was heated at 80° C. for 24 hours. The contents were concentrated. Water was added. The mixture was extracted with DCM (2×) and dried (Na2SO4). The crude material was purified with flash chromatography to give tert-butyl 4-(5-vinyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (855 mg, 20% for 2 steps). 1H NMR (CDCl3, 400 MHz) δ (ppm): 8.47 (s, 1H), 5.95-5.86 (m, 1H), 5.12-5.09 (m, 1H), 4.92-4.87 (m, 1H), 3.98-3.93 (m, 1H), 3.67-3.60 (m, 4H), 3.-3.39 (m, 4H), 2.94-2.76 (m, 2H), 2.35-2.27 (m, 1H), 1.90-1.82 (m, 1H), 1.47 (d, 1.47 (s, 9H). MS: 331.3 (M+1).

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