1,5,6,7-Tetrahydrocyclopenta[d]pyrimidin-4-one

52909-60-1

77287-34-4

5661-01-8

The general procedure for the synthesis of 1,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one from methyl (9ci)-2-amino-1-cyclopentene-1-carboxylate and the compound (CAS:77287-34-4) was as follows: to a solution of ethyl 2-oxo-1-cyclopentanecarboxylate (14a) (1.00 g, 6.40 mmol) in toluene (15 mL) was sequentially 1,1,1-trimethyl-N-(triphenylphosphoranylidene)silylamine (2.24 g, 6.40 mmol), 2-propanol (0.49 mL, 6.40 mmol) and p-toluenesulfonic acid monohydrate (12.2 mg, 0.064 mmol) were added. The reaction mixture was stirred under reflux conditions for 10 hours, then cooled to room temperature, poured into saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the crude product enamine 15a. The crude product 15a was dissolved in formamide (6 mL) and the reaction was stirred at 180 °C for 9 h. The reaction was carried out under reflux conditions. After completion of the reaction, the mixture was poured into saturated brine and extracted with chloroform five times. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using chloroform-methanol (9:1) as eluent to afford the target product 16a (337 mg, 2.47 mmol, 39% overall yield in two steps).