(6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(6-methoxypyridin-3-yl)(thiazol-5-yl)methanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (0.154 mL, 0.246 mmol; 1.6 M in hexane) was added dropwise to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (0.081 g, 0.189 mmol, Intermediate 16) in dry THF (4 mL) at −78° C. over a 5 minute period. After complete addition stirring was continued at −78° C. for 30 minutes then (6-methoxypyridin-3-yl)(thiazol-5-yl)methanone (0.046 g, 0.189 mmol, Intermediate 15) dissolved in THF (1.9 mL) was slowly added and the reaction warmed in an ice bath to 0° C. The mixture was stirred for 30 minutes, quenched with saturated aqueous NH4Cl then warmed to room temperature. After stirring for 10 minutes layers were separated and the aqueous layer extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered, evaporated in vacuo and chromatographed (0-100% EtOAc in DCM) to provide the title compound. 1H NMR (400 MHz, MeOH-d4) δ ppm 3.94 (s, 3H) 4.08 (s, 3H) 4.35 (s, 2H) 6.43-6.52 (m, 1H) 6.88 (d, J=9.09 Hz, 1H) 7.37 (d, J=8.08 Hz, 2H) 7.54-7.63 (m, 3H) 7.66-7.72 (m, 2H) 7.77 (dd, J=8.59, 2.53 Hz, 1H) 7.85 (d, J=8.59 Hz, 1H) 8.12 (dd, J=13.14, 2.53 Hz, 2H) 8.20 (s, 1H) 9.08 (s, 1H); MS (ESI) 570.

Provenance & Evidence