DPC-681-药物合成数据库

【药物名称】DPC-681

化学结构式(Chemical Structure):

参考文献No.	44333
标题:	Bis-amino acid sulfonamides containing N-terminally A substd. benzyl group as HIV protease inhibitors
作者:	Kaltenbach, R.F.; Trainor, G.L. (DuPont Pharmaceuticals Co.)
来源:	EP 1140983; WO 0042060

合成路线图解说明: The protection of the NH group of N-[3(S)-(dibenzylamino)-2(R)-hydroxy-4-phenylbutyl]-N-isobutylamine (I) with Boc2O and TEA in THF gives the carbamate (II), which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol to yield the primary amine (III). The condensation of (III) with N-(benzyloxycarbonyl)-L-tert-leucine (IV) by means of EDC, HOBT and NMM in DMF affords the leucinamide (V), which is deprotected with H2 and Pd/C in methanol, providing the intermediate (VI). The acylation of the free amino group of (VI) with chloroacetyl chloride (VII) and KHCO3 in ethyl acetate/water gives the chloroacetamide (VIII), which is treated with HCl in ethyl acetate/dioxane in order to eliminate the Boc protecting group and yield the secondary amine (IX). The reaction of (IX) with 3-nitrophenylsulfonyl chloride (X) and K2CO3 in THF/water gives the sulfonamide (XI), which is treated with 3-fluorobenzylamine (XII) in refluxing THF to afford the glycyl-tert-leucyl derivative (XIII). Finally, the reduction of the nitro group of (XIII) with H2 over Pd/C in methanol provides the target 3-aminophenylsulfonamide.

合成路线图解说明: The protection of the NH group of N-[3(S)-(dibenzylamino)-2(R)-hydroxy-4-phenylbutyl]-N-isobutylamine (I) with Boc2O and TEA in THF gives the carbamate (II), which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol to yield the primary amine (III). The condensation of (III) with N-(benzyloxycarbonyl)-L-tert-leucine (IV) by means of EDC, HOBT and NMM in DMF affords the leucinamide (V), which is deprotected with H2 and Pd/C in methanol, providing the intermediate (VI). The acylation of the free amino group of (VI) with chloroacetyl chloride (VII) and KHCO3 in ethyl acetate/water gives the chloroacetamide (VIII), which is treated with HCl in ethyl acetate/dioxane in order to eliminate the Boc protecting group and yield the secondary amine (IX). The reaction of (IX) with 4-nitrophenylsulfonyl chloride (X) and K2CO3 in THF/water gives the sulfonamide (XI), which is treated with 3-fluorobenzylamine (XII) in refluxing THF to afford the glycyl-tert-leucyl derivative (XIII). Finally, the reduction of the nitro group of (XIII) with H2 over Pd/C in methanol provides the target 4-aminophenylsulfonamide.