Hydrochloric Acid → HCID 68530704, compound

Participants

Reaction Steps

To a mixture of 2-[2-(2-aminoethoxy)-4-(methylthio)benzoylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamide (1.25 g, 2.47 mmol), paraformaldehyde (312 mg, 10.4 mmol) and methanol (30 mL) was added acetic acid to obtain a pH of 4.0. Sodium cyanoborohydride (311 mg, 4.95 mmol) was added to this mixture. After stirring overnight, the reaction was concentrated, dissolved in 10% MeOH/CHCl3, and passed through an SCX column. The eluent was concentrated and chromatographed on silica gel (1:10 EtOAc:CH2Cl2 to 1:10 MeOH:CH2Cl2) to give impure product. The impure product was dissolved in 5% MeOH/CH2Cl2 and 1 N HCl and stirred for one hour. The mixture was basified with 50% satd sodium carbonate and extracted with CH2Cl2. The organic layer was concentrated and purified by HPLC on a Vydac C18 column [preparative: gradient 20% CH3 CN/(0.01% HCl in H2O) to 80% CH3 CN/(0.01% HCl in H2O) over 6 h on a 5×25 cm column; analytical: 5% CH3 CN/(0.1% TFA in H2O) to 70% CH3 CN/(0.1% TFA in H2O) on a 0.46×25 cm column] to give the title product as a white solid (329 mg, 62%).

Provenance & Evidence