Water → HCID 67171201, compound

Participants

Reaction Steps

A mixture of phosphorus pentoxide (150 mg, 0.528 mmol) and 85% phosphoric acid (0.15 mL, 0.017 mmol) was stirred at 100° C. under nitrogen for 1 hr before 2-amino-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butan-1-ol (Isomer 1 of Example 93, 8 mg, 0.017 mmol) was added. The clear solution was stirred at the same temperature for 3 hr before being cooled. Water (0.4 mL) was added while the mixture was cooled with ice. The mixture was stirred at room temperature for 30 min. The mixture was dissolved in methanol 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 2-amino-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butyl dihydrogen phosphate (5 mg, 8.6 μmol, 52% yield) as a white solid. The compound had an HPLC retention time=3.55 min. (condition C); LC/MS M+1=564.6. 1H NMR (400 MHz, MeOD) δ ppm 7.88 (1H, d, J=7.9 Hz), 7.76 (2H, d, J=7.3 Hz), 7.57-7.69 (3H, m), 7.31 (1H, s), 7.28 (1H, d, J=7.9 Hz), 3.82-3.99 (2H, m), 3.04-3.10 (4H, m), 2.67-2.83 (2H, m), 1.89-2.10 (2H, m), 1.40 (3H, s).

Provenance & Evidence