Triethylamine → Trifluoroacetic acid

Participants

Reaction Steps

To a stirred mixture of 1-((3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid (Example 7, 80 mg, 0.161 mmol), methanesulfonamide (77 mg, 0.807 mmol), DMAP (3.95 mg, 0.032 mmol), triethylamine (0.113 mL, 0.807 mmol), and anhydrous dichloromethane (5 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (92 mg, 0.242 mmol) under nitrogen. The reaction mixture was stirred at room temperature for 5 h before being concentrated. The residue was dissolved in MeOH and a little dichloromethane. Purification using reverse phase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration and lyophilization gave N-(methylsulfonyl)-1-((3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxamide, TFA (15 mg, 0.020 mmol, 12.58% yield) as a white solid. The compound had an HPLC retention time=3.21 min (condition C); LC/MS M+1=573.1. 1H NMR (400 MHz, MeOD) δ ppm 8.08 (1H, d, J=7.9 Hz), 7.64-7.69 (2H, m), 7.54-7.64 (4H, m), 7.51 (1H, dd, J=7.9, 1.8 Hz), 4.48 (2H, s), 4.36 (4H, d, J=7.9 Hz), 3.68 (1H, quin, J=8.0 Hz), 3.27 (3H, s), 3.11-3.22 (4H, m).

Provenance & Evidence