D-Lactic Acid → HCID 67421921, compound

Participants

Reaction Steps

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-[2-methyl-5-(piperazin-1-ylmethyl)phenyl]-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (43-2) (2.3 g, 5.0 mmol, 1.0 eq) was dissolved in NMP (25 mL) and DIPEA (2.6 mL, 14.9 mmol, 3.0 eq), D-lactic acid (536 mg, 6.0 mmol, 1.2 eq) and HATU (2.8 g, 7.4 mmol, 1.5 eq) were added. The reaction mixture stirred at ambient temperature for 5 minutes and was then diluted with EtOAc (200 mL), washed with sodium bicarbonate (4×30 mL) and brine (30 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (120 g SiO2, 0-40% IPA in DCM) to afford (2R)-1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]-2-hydroxypropan-1-one (43-3) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.37 (d, J=8.4 Hz, 1 H); 7.35 (s, 1 H); 7.26 (s, 2 H); 7.08 (d, J=8.4 Hz, 1 H); 4.54 (q, J=6.8 Hz, 1 H); 3.98 (d, J=6.8 Hz, 2 H); 3.64 (m, 4 H); 3.57 (s, 2 H); 3.38 (s, 3 H); 2.49 (m, 4 H); 2.36 (s, 3 H); 2.21 (m, 1 H); 1.67 (m, 1 H); 1.43 (m, 1 H); 1.18 (d, J=6.8 Hz, 3 H). HRMS m/z (M+H) 536.2136 found, 536.2138 required.

Provenance & Evidence