DPC-684

Chemical Name: N-[3-[N-(4-Aminophenylsulfonyl)-N-isobutylamino]-1(S)-benzyl-2(R)-hydroxypropyl]-2(S)-[2-(3-fluorobenzylamino)acetamido]-3,3-dimethylbutyramide; N-(3-Fluorobenzyl)glycyl-L-tert-leucine 3-[N-(4-aminophenylsulfonyl)-N-isobutylamino]-1(S)-benzyl-2(R)-hydroxypropylamide; N-(3-Fluorobenzyl)glycyl-N-[3-[N-(4-aminophenylsulfonyl)-N-isobutylamino]-1(S)-benzyl-2(R)-hydroxypropyl]-3-methyl-L-valinamide
CAS No. 284661-40-1 (diHCl), 284661-73-0 (free base)
项目整合开发状态: Phase I
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线: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: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.