HCID 68313039, compound → HCID 68312701, compound

Participants

Reaction Steps

To a solution of 8-(1-benzyl-3-cyclopropylmethylazetidin-3-yloxy)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (65 mg, 0.124 mmol) in IMS (8 mL) was added Pd(OH)2/C (20 mg) and the reaction mixture was stirred at RT under a hydrogen atmosphere for 16 h. The suspension was then filtered through a pad of Celite® and Pd(OH)2/C (30 mg) was added to the filtrate which was stirred at RT under a hydrogen atmosphere for a further 10 h. The suspension was then filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography (C18, gradient 20-55% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH. Further purification by column chromatography (Si-PCC, gradient 3-12% MeOH in DCM then 10-15% 2M NH3/MeOH in DCM) afforded 284 as a colourless foam (10.4 mg, 19%). LCMS (Method K): RT 2.96 min [M+H]+ 435.1. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=9.0 Hz), 7.67 (1H, s), 6.55 (1H, dd, J=8.9, 2.5 Hz), 6.34 (1H, d, J=2.5 Hz), 5.87 (1H, septet, J=6.6 Hz), 4.48 (4H, s), 3.94 (2H, d, J=10.0 Hz), 3.80 (2H, d, J=10.0 Hz), 2.36 (3H, s), 2.06 (2H, d, J=6.6 Hz), 1.52 (6H, d, J=6.6 Hz), 0.83-0.73 (1H, m), 0.48-0.43 (2H, m), 0.06-0.02 (2H, m)

Provenance & Evidence