Triphenylphosphine → HCID 66558918, compound

Participants

Reaction Steps

To a suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (345 mg, 1.06 mmol), 1-(2,4-dimethylthiazol-5-yl)ethanol (250 mg, 1.59 mmol) and triphenylphosphine (0.84 g, 3.18 mmol) in dioxane (15 mL) was added dropwise DEAD (0.63 mL, 3.18 mmol) and the reaction mixture was stirred at RT for 18 h. Additional amounts of 1-(2,4-dimethylthiazol-5-yl)ethanol (100 mg, 0.63 mmol) and triphenylphosphine (0.42 g, 1.59 mmol) were added, followed by DEAD (0.31 mL, 1.59 mmol) and stirring at RT was continued for 72 h. Volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was further purified by column chromatography (Si-PCC, gradient 0-6% MeOH in EtOAc then C18, gradient 15-70% MeOH in H2O) and finally loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH affording 188 as a white solid (60 mg, 12%). LCMS: RT 4.42 min [M+H]+ 465.1. 1H NMR (CDCl3, 400 MHz): δ 8.33 (1H, d, J=9.33 Hz), 7.53 (1H, s), 6.65 (1H, dd, J=9.33 and 2.56 Hz), 6.46 (1H, d, J=2.71), 5.91-5.81 (1H, m), 5.54-5.48 (1H, m), 4.44-4.29 (4H, m), 2.57 (3H, s), 2.39 (3H, s), 2.37 (3H, s), 1.65 (3H, d J=6.22 Hz), 1.52 (6H, d, J=6.72 Hz)

Provenance & Evidence