(1-isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-yl)-carbamic acid benzyl ester → 1-Isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-ylamine

Participants

Reaction Steps

A suspension of (1-isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-yl)-carbamic acid benzyl ester (157 mg, 0.25 mmol) in IMS (25 mL) was treated with a slurry of palladium on carbon (50 mg, 50% in water) and the mixture was stirred under an atmosphere of hydrogen for 3 days. More palladium on carbon was added and the mixture stirred for another 18 hours before being filtered through celite. The filtrate was concentrated in vacuo and the residue purified by reverse-phase preparative HPLC (Gemini C18 column, gradient 10-90% MeOH in H2O+0.1% HCO2H) to give 463 as a white solid after freeze drying (43 mg, 35%). LCMS: RT=6.30 min, [M+H]+=489. 1H NMR δ (ppm) (DMSO-d6): 8.22 (1 H, d, J=8.18 Hz), 7.14 (1 H, dd, J=8.25, 1.81 Hz), 6.99 (1 H, d, J=1.77 Hz), 5.67-5.59 (1 H, m), 5.54 (2 H, s), 4.30 (2 H, t, J=5.02 Hz), 3.63-3.50 (3 H, m), 3.10 (4 H, t, J=6.28 Hz), 3.01 (3 H, s), 2.78 (2 H, t, J=6.83 Hz), 1.42 (6 H, d, J=6.58 Hz). 2 Protons obscured by water peak

Provenance & Evidence