1,2,3,4-Tetrahydroquinoline → [4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone

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Reaction Steps

To a solution of 0.16 g (0.56 mmol) 4-(2,5-dichloro-phenoxy)-nicotinic acid in 3 mL N,N-dimethylformamide were added 0.225 g (0.59 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 0.29 mL (1.69 mmol) N,N-diisopropylethylamine. To the light yellow solution 0.07 mL (0.59 mmol) 1,2,3,4-tetrahydroquinoline (commercially available; CAS RN 635-46-1) was added and the resulting light yellow solution was stirred at room temperature for 23 hours. The reaction mixture was poured on water and extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50). The product-containing fractions were combined and evaporated to give 165 mg (73%) of the desired compound as a light brown solid. MS (ESI): m/z=399.06 [M+H]+.

Provenance & Evidence