To a stirring solution of 2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazole-7-carbaldehyde (Preparation 56F, 352 mg, 0.825 mmol) and azetidine-3-carboxylic acid (100 mg, 0.990 mmol) in MeOH (5 mL) and 1,2-dichloroethane (5.00 mL) was added at room temperature about 3-4 drops of AcOH. The reaction mixture was immersed in an oil bath heated at 80° C. and stirred for 1 h. It was cooled to room temperature and was treated with sodium cyanoborohydride (62.2 mg, 0.990 mmol), which was added in one portion. The reaction mixture was stirred at room temperature for 1 h, concentrated, and half of the material was purified by prep. HPLC (HPLC conditions: Phenomenex Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min.) to yield 1-((2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)methyl)azetidine-3-carboxylic acid, TFA (12 mg, 0.019 mmol, 2.279% yield) as a fluffy light yellow solid. The product had an LC ret. time=3.155 min. (condition: Start % B=0, Final % B=100, Gradient Time=4 min, Flow Rate=4 ml/min, Wavelength=220, Solvent Pair=MeOH−H2O−TFA; Solvent A=10% MeOH−90% H2O−0.1% TFA; Solvent B=90% MeOH−10% H2O−0.1% TFA; Column 1=1: Waters Sunfire C18 4.6×50 mm (4 min. grad)); LC/MS M+1=512.12. 1H NMR (400 MHz, CD3OD) δ ppm 7.65 (1H, s), 7.63 (1H, d, J=1.32 Hz), 7.53-7.62 (4H, m), 7.46 (1H, s), 7.41 (1H, dd, J=7.92, 1.76 Hz), 4.42 (2H, s), 4.34 (2H, d, J=3.08 Hz), 4.32 (2H, d, J=1.10 Hz), 3.60-3.70 (1H, m), 3.21 (4H, s).
