Ammonia → HCID 67167593, compound

Participants

Reaction Steps

To a stirred mixture of 3-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)cyclopentanone (prepared according to Preparation 121C from 5-(7-iodo-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole (Preparation 123A), 200 mg, 0.416 mmol), 7 M methanol solution of ammonia (2 mL, 14.00 mmol), and anhydrous dichloromethane (1.5 mL) was added allylboronic acid pinacol ester (0.117 mL, 0.624 mmol). The mixture was stirred at room temperature overnight. More allylboronic acid pinacol ester (0.1 mL) was added. The mixture was stirred at room temperature for 5 h before being concentrated. The residue was mixed with water (5 mL) and extracted with dichloromethane (4×2 mL). The combined dichloromethane extracts were dried (sodium sulfate) and concentrated under reduced pressure. 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, neutralization with saturated aqueous sodium bicarbonate solution and extraction with dichloromethane gave 1-allyl-3-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)cyclopentanamine (103 mg, 0.197 mmol, 47.4% yield) as a glassy solid. The compound had an HPLC retention time=3.75 min. (condition C); LC/MS M+1=521.9.

Provenance & Evidence