Hydrochloric Acid → HCID 58826034, compound

Participants

Reaction Steps

To a suspension of compound 5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.0 g, 2.5 mmoles), Boc-DL-valine (1.22 g, 5.6 mmoles), and 4-dimethylaminopyridine (1.0 g, 8.2 mmoles) in dichloromethane, was added 1,3-dicyclohexylcarbodiimide (2.4 g, 11.6 mmoles). The mixture was stirred at room temperature for 60 hours, and solids were filtered off. The filtrate was evaporated and the residue was dissolved in a mixture of concentrated aqueous ammonium hydroxide and methanol (5 ml/45 ml) and stirred at room temperature for 5 hours. Solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and 0.5 N aqueous HCl. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (30% ethyl acetate in hexane) to give Boc-protected 2-Amino-N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-3-methyl-butyramide as a white foam (0.2 g), MS (M+H)=600. This Boc compound was dissolved in dichloromethane (3 ml) and 1M HCl in diethyl ether (10 ml) was added. The mixture was stirred for 4 hours at room temperature, and 10 ml of additional diethyl ether was added. The resulting solid precipitate was collected and crystallized from isopropanol and ether to give 2-amino-N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-3-methyl-butyramide as white solid (0.12 g), MS (M+H)=500.

Provenance & Evidence