新产品编号:812075

Chemical Name: 4(R)-Hydroxy-1-(3,3,3-triphenylpropionyl)-L-prolyl-N-[1-propylpiperidin-3(R)-ylmethyl]-D-prolinamide
CAS No. 323182-47-4, 323182-76-9 (diastereomer)
项目整合开发状态: Biological Testing
项目研究机构: Banyu (Originator), Merck & Co. (Originator)
合成路线:Coupling between ethyl 3-aminopropionate (I) and N-Boc-glycine (II) by means of EDC and HOBt affords the protected dipeptide (III).After acidic Boc group cleavage in (III),the N-deprotected dipeptide (IV) is acylated by 3,3,3-triphenylpropionic acid (V) to produce amide (VI).Saponification of the ethyl ester group of (VI) yields acid (VII).This is coupled with (R)-1-Boc-3-(aminomethyl)piperidine (VIII) to afford amide (IX),which is further subjected to acidic N-Boc group cleavage.The resultant piperidine derivative (X) is then reductively condensed with cyclohexanecarboxaldehyde (XI) in the presence of NaBH(OAc)3 to furnish the title compound.

合成路线:Esterification of N-benzyloxycarbonyl-D-proline (I) with MeOH in the presence of EDC,followed by deprotection of the resultant N-Cbz amino ester (II) with H2 and Pd(OH)2 leads to D-proline methyl ester (III).Subsequent coupling of (III) with N-benzyloxycarbonyl-O-t-butyl-L-4-trans-hydroxyproline (IV) yields the protected dipeptide (V).After removal of the N-benzyloxycarbonyl group of (V) by catalytic hydrogenolysis,the free amine (VI) is acylated by 3,3,3-triphenylpropionic acid (VII),producing amide (VIII).The methyl ester group of (VIII) is then hydrolyzed under alkaline conditions to furnish acid (IX).

合成路线:Coupling of acid (IX) with (R)-3-(aminomethyl)-1-Boc-piperidine (X) gives the triamide (XI).Deprotection of both N-Boc and O-t-butyl groups of (XI) with trifluoroacetic acid affords (XII).Finally,reductive alkylation of piperidine (XII) with propionaldehyde in the presence of NaBH3CN/ZnCl2 provides the target compound.