PD-168787, CI-1018

6,8-二氧杂二环[3.2.1]辛烷,2-氟-1,5-二甲基-,(1R,2R,5R)-Chemical Name: N-[9-Methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzodiazepin-3(R)-yl]pyridine-4-carboxamide
CAS No. 179024-48-7
项目整合开发状态: Phase I
项目研究机构: Jouveinal (Originator), Pfizer (Originator)
合成路线:The condensation of 5-methylindoline (I) with benzonitrile (II) by means of BCl3 and AlCl3 in dichloroethane gives the 7-benzoyl-5-methylindoline (III),which is cyclized with glycine methyl ester (IV) in pyridine yielding the tricyclic pyrrolobenzodiazepinone (V).The reaction of (V) with isoamyl nitrite and potassium tert-butoxide in THF affords the oxime (VI),which is reduced with H2 over Ru/C in methanol providing the racemic amine (VII).The optical resolution of (VII) with N-acetyl-L-phenylalanine gives the desired isomer (VIII),which is finally condensed with pyridine-4-carboxylic acid (IX) by means of O-[1-(ethoxycarbonyl)-1-cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU) and DIEA in dichloromethane.