新产品编号:1408489

Chemical Name: (3R,4S,5R,5aS,7R,8R)-3-Benzyl-7-benzyloxy-4,5-dihydroxy-2-(1H-indazol-5-ylmethyl)perhydro-5a,8-ethanopyrrolo[1,2-c][1,3]diazepin-1-one
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The chiral bicyclic alcohol (I) was converted to the benzyl ether (II) using benzyl bromide and NaH.Subsequent reduction of the ester group of (III) with LiBH4 provided primary alcohol (III),and further Swern oxidation yielded aldehyde (IV).Pinacol coupling of (IV) with D-phenylalaninal (V) by means of VCl3 - (THF)3 and Zn furnished diol (VI) with 85% diastereoselectivity.This was protected as the acetonide (VIII) upon treatment with 2,2-dimethoxypropane (VII) and camphorsulfonic acid.Selective removal of the two N-benzyloxycarbonyl groups of (VIII) by hydrogenation in the presence of Pd/C and NH3 gave diamine (IX),which was cyclized to the urea (X) employing carbonyldiimidazole and pyridine.

合成路线:After N-alkylation of (X) with the protected bromomethylindazole (XI) to give (XII),acid hydrolysis of the acetonide yielded diol (XIII).In order to invert the undesired configuration at C4,the 4-hydroxyl group of (XIII) was selectively oxidized under Swern conditions to produce hydroxyketone (XIV).Subsequent reduction of (XIV) with ethanolic NaBH4 provided the required (4S,5R)-diol (XV).The silylethoxymethyl protecting group was finally removed with tetrabutylammonium fluoride in THF to afford the title compound.