Triethylamine → N-[7-(3,5-dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinyl]tetrahydro-2H-pyran-4-carboxamide

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Reaction Steps

To a solution of tetrahydro-2H-pyran-4-carboxylic acid (0.381 g, intermediate 69) in DCM (60 ml) were successively added triethylamine (0.41 ml) then HATU (1.115 g) and the resulting mixture was stirred for 20 min room temperature. 7-(3,5-dimethyl-4-isoxazolyl)-N4-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-6-(methyloxy)-3,4-quinolinediamine (0.6 g, intermediate 69) was added and the mixture stirred at ambient temperature overnight. The reaction mixture was poured into water and extracted with DCM. The organic phase was washed with a dilute sodium hydroxide solution and then with water. The organic phase was dried over Na2SO4 and concentrated to dryness. The crude residue was purified by flash silica gel chromatography eluting DCM/methanol (99:1 then 95:5) to give the desired product as a beige sticky solid (0.71 g). The solid was triturated with hot diisopropylether to give N-[7-(3,5-dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinyl]tetrahydro-2H-pyran-4-carboxamide (0.6 g) as cream coloured crystals.

Provenance & Evidence