合成路线:The reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I) gives the pyrrolobenzodiazepine (II),which is acylated with 2-chloro-4-nitrobenzoyl chloride (III) giving the expected 10-benzoyl derivative (IV).The reduction of the nitro group of (IV) with H2 over Pd/C or with SnCl2 yields the corresponding 4-amino derivative (V),which is finally acylated with 5-fluoro-2-methylbenzoyl chloride.
合成路线:The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII),which is hydrolyzed at the ester group yielding the corresponding free acid (IX).The reaction of (IX) with SOCl2 affords the acyl chloride (X),which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
参考文献标题:Tricyclic diazepine vasopressin antagonists and oxytocin antagonists
文献作者:Reich,M.F.; Delos Santos,E.G.; Sum,F.-W.; Albright,J.D.(American Cyanamid Co.)
参考来源:US 5733905
合成路线:The reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I) gives the pyrrolobenzodiazepine (II),which is acylated with 2-chloro-4-nitrobenzoyl chloride (III) giving the expected 10-benzoyl derivative (IV).The reduction of the nitro group of (IV) with H2 over Pd/C or with SnCl2 yields the corresponding 4-amino derivative (V),which is finally acylated with 5-fluoro-2-methylbenzoyl chloride.
合成路线:The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII),which is hydrolyzed at the ester group yielding the corresponding free acid (IX).The reaction of (IX) with SOCl2 affords the acyl chloride (X),which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
参考文献标题:Tricyclic diazepine vasopressin antagonists and oxytocin antagonists
文献作者:Albright,J.D.; Sum,F.-W.; Delos Santos,E.G.; Reich,M.F.(American Cyanamid Co.)
参考来源:US 5736540
合成路线:The reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I) gives the pyrrolobenzodiazepine (II),which is acylated with 2-chloro-4-nitrobenzoyl chloride (III) giving the expected 10-benzoyl derivative (IV).The reduction of the nitro group of (IV) with H2 over Pd/C or with SnCl2 yields the corresponding 4-amino derivative (V),which is finally acylated with 5-fluoro-2-methylbenzoyl chloride.
合成路线:The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII),which is hydrolyzed at the ester group yielding the corresponding free acid (IX).The reaction of (IX) with SOCl2 affords the acyl chloride (X),which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
合成路线:The pyrrolobenzodiazepine (I) is prepared in two steps.The sodium salt of pyrrole-2-carboxaldehyde (II) is prepared in DMF using NaH.Alkylation with 2-nitrobenzyl bromide (III) proceeds in excellent yield.Reduction with hydrogen over Raney nickel effects reduction of the nitro group to the amine which cyclizes in situ to the seven-membered imine that is reduced to the pyrrolobenzodiazepine in excellent yield in one pot.
参考文献标题:5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): An orally active arginine vasopressin antagonist with selectivity for V2 receptors
文献作者:Albright,J.D.; Reich,M.F.; Delos Santos,E.G.; Dusza,J.P.; Sum,F.W.; Venkatesan,A.M.; Coupet,J.; Chan,P.S.; Ru,X.; Mazandarani,H.; Bailey,T.
参考来源:J Med Chem 1998,41(14),2442
产品链接: CAS No. 168079-32-1››