SM-20302

Chemical Name: 3-[3-(4-Amidinobenzamido)propionamido]-2(S)-(4-ethylphenylsulfonamido)propionic acid
CAS No. 169456-85-3, 169456-86-4 (monotrifluoroacetate)
项目整合开发状态: Preclinical
项目研究机构: Sumitomo Pharmaceuticals (Originator)
合成路线:The reaction of N-(benzyloxycarbonyl)-L-asparagine (I) with bis(trifluoroacetyl)iodobenzene (BTI) in DMF/water gives 3-amino-2(S)-(benzyloxycarbonylamino)propionic acid (II),wehich is protected at the amino group with tert-butoxycarbonyl anhydride yielding carbamate (III).The esterification of (III) with ethanol WSC and DMAP affords the expected ethyl ester (IV),which is selectively deprotected with methanesulfonic acid in acetonitrile providing 3-amino-2-(benzyloxycarbonylamino)propionic acid ethyl ester (V).The condensation of (V) with N-(tert-butoxycarbonyl)-beta-alanine (VI) by means of HOBT,WSC and triethylamine in DMF gives the protected propionamidopropionic ester (VII),which is selectively deprotected by hydrogenation with H2 over Pd/C in ethanol/ethyl acetate giving the 2-aminopropionic ester (VIII).The condensation of (VIII) with 4-ethylbenzenesulfonyl chloride (IX) by means of triethylamine in dichloromethane yields the sulfonamide (X),which is deprotected with methanesulfonic acid as before afording intermediate (XI) with a free amino group,which is condensed with 4-(tert-butoxycarbonylamino)benzoic acid (XII) by means of HOBT and WSC in DMF providing the fully protected target compound (XIII).

合成路线:The deprotetion of (XIII) first with trifluoroacetic acid gives the ethyl ester (XIV),which is finally hydrolyzed with HCl in hot acetic acid.

合成路线:The intermediate 4-(tert-butoxycarbonylamindino)benzoic acid (XII) has been obtained as follows: Comerciaally available 4-amidinobenzamide (XV) is hydrolyzed with aqueous HCl to give 4-amidinobenzoic acid (XVI),which is then treated with tert-butoxycarbonyl anhydride and N,O-bis(trimethylsilyl)acetamide in dichloromethane to afford the target intermediate (XII).