BMS-433771

1-环丙基-3-((1-(3-羟丙基)-1H-苯并[d]吡达唑-2-基甲基)-1H-吡啶[4,5-c]吡啶-2(3H)-1Chemical Name: 1-Cyclopropyl-3-[1-(3-hydroxypropyl)-1H-benzimidazol-2-ylmethyl]-2,3-dihydro-1H-imidazo[4,5-c]pyridin-2-one
CAS No. 380603-10-1
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Synthesis of benzimidazole intermediate (VIII) was achieved as follows.The reaction of 2,5-difluoronitrobenzene (I) with 3-methoxypropylamine (II) by means of K2CO3 in acetonitrile gives the aniline (III),which is reduced with Fe and NH4Cl in water to yield the phenylenediamine (IV).The cyclization of (IV) with glycolic acid (V) in refluxing 4N HCl affords the benzimidazolylmethanol (VI).Finally,this compound is brominated with (bromomethylene)dimethylammonium bromide (VII) in acetonitrile to provide the target bromomethylbenzimidazole intermediate (VIII).The reaction of 4-methoxy-3-nitropyridine (IX) with cyclopropylamine (X) in refluxing ethanol gives the N-cyclopropyl-3-nitropyridine-4-amine (XI),which is reduced with H2 over Pd/C in methanol to yield the pyridinediamine (XII).The cyclization of (XII) with phosgene in acetonitrile affords 1-cyclopropyl-2,3-dihydro-1H-imidazol[4,5-c]pyridin-2-one (XIII),which is condensed with bromomethyl intermediate (VIII) by means of NaH in THF,DMF or acetonitrile to provide the adduct (XIV).Finally,this compound is demethylated by means of BBr3 in dichloromethane to furnish the target 3-hydroxypropyl compound.