Diisopropylethylamine → (3S)-tert-butyl 3-methyl-4-(5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-chloro-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidine (5 g, 27 mmol) and 2-(S)-methyl-4-Boc-piperazine (5.4 g, 27 mmol) in NMP (20 mL) was added DIEA (5 mL, 29 mmol). The mixture was heated to 120° C. for 24 hours. After cooling, the mixture was diluted with ethyl acetate (500 mL) and washed with water (6×200 mL). The organic phase was dried and concentrated to afford (3S)-tert-butyl 3-methyl-4-(5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate (6 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 8.55 (s, 1H), 4.81 (m, 1H), 4.45 (m, 1H). 4.18 (m, 3H), 3.90 (m, 1H), 3.75 (m, 1H), 3.44-3.29 (m, 2H), 2.96 (m, 1H), 1.52 (m, 12H), 1.14 (d, J=6.4 Hz, 3H). MS (APCI+) [M+H]+ 351. The residue was purified by chiral HPLC separation (OD 250×20 mm; acetonitrile, 2 mL/min). The first peak (RT=3.93 min) was (S)-tert-butyl 3-methyl-4-((R)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate and the secondary (RT=4.26 min) was (S)-tert-butyl 3-methyl-4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate.

Provenance & Evidence