Dimethyl Sulfoxide → (R)-2-{(R)-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butan-1-ol

Participants

Reaction Steps

Charge (R)-4-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide (0.10 g), D-valinol (46.8 mg,), and DMSO (2 mL) to a 3 neck round bottom flask with temp. probe, nitrogen inlet and stir bar. Charge diisopropylethylamine (0.1 mL) and heat the mixture to 80° C. with stirring for 2 h. Cool the mixture to ambient temperature and charge water slowly (3-5 mL) which precipitates the product as an off-white solid. Filter the solid and rinse it with water. Dry the solid for 12 h at 50° C. under vacuum providing (R)-2-{(R)-2-[4-(4-Chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butan-1-ol (0.21 g, 92% yld.) as a off-white solid. Recrystallize from IPA/H2O (15 vols/0.5 vols) to give material of >99% purity. 1H NMR (400 MHz, CDCl3) δ 7.16-7.26 (m, 2H), 7.00 (bs, 1H), 6.80-6.90 (m, 2H), 4.02-4.12 (m, 1H), 3.90-4.00 (m, 4H), 3.68-3.85 (m, 3H), 3.55-3.65 (m, 1H), 3.35-3.45 (m, 1H), 3.12-3.20 (m, 4H), 2.94-3.08 (m, 2H), 1.92-2.06 (m, 1H), 0.95 (d, J=6.5 Hz, 3H), 0.90 (d, J=6.5 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 174.6, 163.1, 160.4, 150.1, 129.4, 125.3, 118.0, 107.6, 63.9, 58.6, 49.6, 44.1, 33.0, 29.7, 20.2, 19.8 (5 signals missing due to overlap); LCMS (ESI) for C21H29ClN5O2S (M+H)+: calcd. 450.2, obsvd. 450.1.

Provenance & Evidence