1-Fluoro-2-fluoromethyl-3-butyn-2-ol → 8-Fluoro-9-(4-fluoro-3-fluoromethyl-3-hydroxy-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

Participants

Reaction Steps

The title compound was prepared according to a procedure similar to that described in Procedure G. Into a 10-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed a suspension of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide (200 mg, 0.58 mmol, 1.00 equiv), 1-fluoro-2-(fluoromethyl)but-3-yn-2-ol (280 mg, 1.75 mmol, 3.00 equiv) and Pd(PPh3)Cl2 (82 mg, 0.20 equiv) in DMSO (0.7 mL) and triethylamine (0.7 mL). The final reaction mixture was irradiated with microwave radiation for 1 h at 70° C. The resulting solution was diluted with 15 mL of water. The resulting solution was extracted with 3×15 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with DCM:MeOH (10:1). This resulted in 72.9 mg (32%) of 8-Fluoro-9-(4-fluoro-3-fluoromethyl-3-hydroxy-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid. LC-MS: (ES, m/z): 383[M+H]+; 1H-NMR: (400 MHz, CD3OD, ppm) δ 8.735 (d, 1H), 6.875 (d, 1H), 4.559 (d, 4H), 4.400 (t, 2H), 3.450 (t, 2H).

Provenance & Evidence