Sodium Carbonate → N-(4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-{4-[2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide (300 mg, 0.645 mmol, Example 7(d)), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (216 mg, 0.70 mmol, Aldrich), Pd(OAc)2 (7.2 mg, 0.03 mmol, Aldrich), PPh3 (17 mg, 0.065 mmol) and 2N aqueous Na2CO3 (0.65 mL) in 1,2-dimethoxyethane (3.0 mL) was heated at 120° C. in a microwave synthesizer for 25 min. The reaction mixture was cooled to room temperature, diluted with saturated aqueous solution of NaHCO3 (10 mL) and extracted with EtOAc (2×50) mL. The combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The yellow solid residue was dissolved in DCM (4 mL) and treated with trifluoroacetic acid (1 mL). The mixture was stirred at room temperature for 1.5 h and the volatiles were evaporated in vacuo. The residue was partitioned between 1N HCl (5 mL) and Et2O (5 mL). The aqueous layer was separated, basified with 2N NaOH, and extracted with EtOAc (3×15 mL). The combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue by silica gel column chromatography (gradient 1-25% (2N NH3 in MeOH)/EtOAc) afforded the title compound as an off-white solid. MS (ESI, pos. ion.) m/z: 512 (M+1).

Provenance & Evidence