Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-Chloro-3-[(2-Cyanopropan-2-Yl)oxy]-N-{5-[{2-[(Cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-B]pyridin-5-Yl}(Methyl)amino]-2-Fluorophenyl}benzamide

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Reaction Steps

To a solution of 2-chloro-3-(1-cyano-1-methylethoxy)benzoic acid (4.8 g, 20 mmol) produced in Example C70(iii) in pyridine (100 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (7.6 g, 20 mmol), and the mixture was stirred at room temperature for 2 hr. To the obtained solution was added N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (3.57 g, 9.99 mmol), and the mixture was stirred at 90° C. for 3 hr. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (350 mL), and washed with water (350 mL). The aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (250 mL×2) and saturated brine (250 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=60/40→20/80), the obtained solution was concentrated under reduced pressure, and the residue was crystallized from ethyl acetate to give the title compound (5.02 g, 87%) as a colorless powder.

Provenance & Evidence