2-Hydroxyisobutyric acid → 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}-2-methyl-propan-1-one

Participants

Reaction Steps

Following the procedure for 318, 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 and 2-hydroxyisobutyric acid were reacted in DMF. Purification by trituration with ether then reverse phase preparative HPLC (Gemini C18 column, gradient 40-98% MeOH in H2O+0.1% HCO2H) gave 444 as a white solid (39 mg, 21%). LCMS: RT=11.04 min, [M+H]+=454. 1H NMR δ (ppm) (CDCl3): 8.36 (1 H, d, J=8.19 Hz), 7.90 (1 H, s), 7.11 (1 H, dd, J=8.22, 1.90 Hz), 7.00-6.96 (1 H, m), 5.92-5.83 (1 H, m), 4.74 (1 H, d, J=9.42 Hz), 4.46 (1 H, t, J=9.76 Hz), 4.39 (3 H, t, J=5.47 Hz), 4.14 (1 H, s), 3.87-3.78 (1H, m), 3.65 (1H, s), 3.40 (2 H, t, J=5.00 Hz), 1.60 (6 H, d, J=6.63 Hz), 1.43 (6H, s)

Provenance & Evidence