CRA-0316
Chemical Name: 1-[7-[2,6-Dibromo-4-(trifluoromethyl)phenyl]-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-1,2,3,6-tetrahydropyridine-4-carboxamide
CAS No. 291538-79-9
项目整合开发状态: Preclinical
项目研究机构: Taisho (Originator)
合成路线:The preparation of the intermediate 1,2,3,6-tetrahydropyridine-4-carboxamide (VI) is illustrated in Scheme 1.Demethylation of tetrahydropyridine (I) with ethyl chloroformate in refluxing benzene affords carbamate (II),which is further hydrolyzed to the aminoacid (III) upon heating with concentrated HBr.Subsequent protection of (III) by means of di-t-butyl dicarbonate leads to N-Boc tetrahydropyridine-4-carboxylic acid (IV).Coupling of acid (IV) with ammonia in the presence of EDC/HOBt provides amide (V).The N-Boc protecting group of (V) is then removed with trifluoroacetic acid in CHCl3,yielding tetrahydropyridine (VI)
合成路线:Condensation of 2,6-dibromo-4-(trifluoromethyl)aniline (VII) with acetoin (VIII),followed by heating the intermediate imine (IX) with malononitrile at 180 C gives rise to the N-aryl pyrrole (X).Acylation of aminopyrrole (X) with Ac2O provides acetamide (XI),which undergoes ring closure to the pyrrolopyrimidine (XII) in hot phosphoric acid.Chlorination of (XII) employing POCl3 furnishes aryl chloride (XIII).This is finally condensed with tetrahydropyridine (VI) to produce the title compound
📌 参考资料/链接：
参考文献标题:Carbamoyl tetrahydropyridine derivs.
文献作者:Tomisawa,K.; Kumagai,T.; Nakazato,A.; Okubo,T.(Taisho Pharmaceutical Co.,Ltd.)
参考来源:EP 1176146
📄 详细内容
合成路线:Condensation of 2,6-dibromo-4-(trifluoromethyl)aniline (VII) with acetoin (VIII),followed by heating the intermediate imine (IX) with malononitrile at 180 C gives rise to the N-aryl pyrrole (X).Acylation of aminopyrrole (X) with Ac2O provides acetamide (XI),which undergoes ring closure to the pyrrolopyrimidine (XII) in hot phosphoric acid.Chlorination of (XII) employing POCl3 furnishes aryl chloride (XIII).This is finally condensed with tetrahydropyridine (VI) to produce the title compound
参考文献标题:Synthesis,SARs and biological activities of CRH1 receptor: Novel 3- or 4-carbamoyl-1,2,5,6-tetrahydropyridinopyrrolopyrimidine derivative
文献作者:Oshida,Y.; Kumagai,T.; Okubo,T.; Chaki,S.; Okuyama,S.; Nakazato,A.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 259
合成路线:Condensation of 2,6-dibromo-4-(trifluoromethyl)aniline (VII) with acetoin (VIII),followed by heating the intermediate imine (IX) with malononitrile at 180 C gives rise to the N-aryl pyrrole (X).Acylation of aminopyrrole (X) with Ac2O provides acetamide (XI),which undergoes ring closure to the pyrrolopyrimidine (XII) in hot phosphoric acid.Chlorination of (XII) employing POCl3 furnishes aryl chloride (XIII).This is finally condensed with tetrahydropyridine (VI) to produce the title compound
参考文献标题:4- or 5-Carbamoyl-1,2,3,6-tetrahydropyridinopyrrolopyrimidine derivative as a CRH1 receptor antagonist
文献作者:Okubo,T.; et al.
参考来源:Drugs Fut 2002,27(Suppl.A),