Hydrochloric Acid → Ethyl 4-(3-(4-(dimethylamino)benzamido)-2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate

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Reaction Steps

To a solution of N-(3-(2-amino-1-(6-morpholino-1H-indol-3-yl)ethyl)-2-fluorophenyl)-4-(dimethylamino)benzamide (0.321 g, 0.640 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.279 mL, 1.408 mmol) in 1,4-dioxane (30 mL) at room temperature was added hydrogen chloride (4 N in 1,4-dioxane) (0.480 mL, 1.92 mmol). The mixture turned to heterogeneous and it was stirred room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (30 mL), basified with NaHCO3 solution to pH 10, and extracted with ethyl acetate (4×40 mL). The combined extract was washed with brine (30 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added 1,4-dioxane (1 mL) and p-xylem (15 mL) and 10% Pd/C (0.4 g), and the mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (120 ml), washed with brine (25 ml), and dried over anhydrous MgSO4. Removal of solvent under vacuum, followed by triturating with Et2O (8 mL), provided the desired product (0.144 g, 0.238 mmol, 37.1% yield) as a tan solid.

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