D-Lactic Acid → (R)-2-hydroxy-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-propan-1-one

Participants

Reaction Steps

To a suspension of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (200 mg, 0.42 mmol) in THF (3 mL) was added diisopropylethylamine (0.22 mL, 1.26 mmol), HATU (175 mg, 0.46 mmol) and D-(−)-lactic acid (41 mg, 0.46 mmol). The reaction mixture was stirred at RT for 18 hours and then concentrated in vacuo. The resultant residue was partitioned between DCM and an aqueous saturated sodium bicarbonate solution and the organic layer was washed with water followed by brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in DCM) to give a cream solid that was freeze-dried from methanol and water to give 318 as a white solid (59 mg, 32%). LCMS: RT=4.44 min, [M+H]+=440. 1H NMR δ (ppm) (DMSO-d6): 8.30 (1H, d, J=8.19 Hz), 8.05 (1H, s), 7.18 (1H, ddd, J=8.24, 4.14, 1.84 Hz), 7.01 (1H, s), 5.82-5.72 (1H, m), 5.04 (1H, s), 4.65-4.55 (1H, m), 4.35-4.29 (2H, m), 4.28-4.17 (2H, m), 4.11 (1H, dd, J=13.38, 6.69 Hz), 3.86-3.75 (2H, m), 3.42-3.36 (2H, m), 1.50 (6H, d, J=6.59 Hz), 1.16 (3H, d, J=6.70 Hz)

Provenance & Evidence