合成路线1

L-697,661 was prepared via a convergent route: Formylation of 2-pentanone (I) with ethyl formate and sodium methoxide gave the ketoaldehyde sodium salt (II). When a mixture of anhydrous diethyl ether and absolute ethanol, 6:1 v/v, was used as solvent, the desired regioisomer precipitated out of solution. Treatment of ethyl nitroacetate (III) with ethanol saturated with ammonia provided nitroacetamide ammonium salt (IV). The nitroacetamide was then condensed with (II) in an aqueous solution of piperidinium acetate to afford the 3-nitropyridinone (V). Catalytic reduction of (V) provided the 3-aminopyridinone (VI). Treatment of chloroacetonitrile (VII) with hydrogen chloride and absolute ethanol gave ethyl chloroiminoacetate hydrochloride (VIII). Nitration of 2,4-dichlorophenol (IX), followed by catalytic reduction of the resultant product, led to the aminophenol (X). Coupling of (X) with (VIII) yielded the chloromethylbenzoxazole (XI), which was converted to the corresponding iodomethyl derivative (XII). Alkylation of the 3-aminopyridinone (VI) with the iodomethylbenzoxazole (XII) furnished L-697,661.