【药物名称】PD-174424
化学结构式(Chemical Structure):
参考文献No.623815
标题:Utilization of an intramolecular hydrogen bond to increase the CNS penetration of an NK1 receptor antagonist
作者:Ashwood, V.A.; Field, M.J.; Horwell, D.C.; Julien-Larose, C.; Lewthwaite, R.A.; McCleary, S.; Pritchard, M.C.; Raphy, J.; Singh, L.
来源:J Med Chem 2001,44(14),2276
合成路线图解说明:

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.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us