PD-174424

Chemical Name: N2-(Benzofuran-2-ylmethoxycarbonyl)-alpha-(dimethylaminomethyl)-N1-[1(S)-phenylethyl]-D-tryptophanamide hydrochloride; N-[1(S)-(Dimethylaminomethyl)-2-(1H-indol-3-yl)-1-[N-[1(S)-phenylethyl]carbamoyl]ethyl]carbamic acid benzofuran-2-ylmethyl ester hydrochloride
CAS No. 354117-39-8 (free base)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Esterification of N-benzyloxycarbonyl-(R)-tryptophan (I) with allyl alcohol (II) using DCC gave ester (III).The cyclization of (III) to afford diastereoselectively the pyrroloindole derivative (IV) was achieved in trifluoroacetic acid as the solvent.A second N-benzyloxycarbonyl protecting group was then introduced at the indoline nitrogen of (IV),yielding (V).Mannich reaction of the lithium anion of (V) with Eschenmoser's salt provided the (dimethylamino)methyl compound (VI).Ring opening of (VI) to the indole (VII) was performed with sulfuric acid in aqueous methanol.The allyl ester of (VII) was then removed by means of morpholine and palladium catalyst to produce acid (VIII),which was coupled with (S)-alpha-methylbenzylamine (IX) to give amide (X).After hydrogenolysis of the two benzyloxycarbonyl protecting groups of (X),the free amine (XI) was acylated with 2-benzofuranylmethyl chloroformate to furnish the title carbamate.