A-373857
Chemical Name: 5-[1-(4-Cyanophenyl)-1-(1-methyl-1H-imidazol-5-yl)methoxymethyl]-6-(2,2-difluoro-1,3-benzodioxol-5-yl)pyridine-2-carbonitrile
CAS No. 450839-23-3
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:2-Bromo-3-methylpyridine (I) is converted to the corresponding N-oxide (II) by treatment with m-chloroperbenzoic acid in CH2Cl2.Reaction of N-oxide (II) with trimethylsilyl cyanide and dimethylcarbamoyl chloride gives rise to the 2-cyanopyridine (III).Subsequent radical bromination of (III) using NBS and AIBN affords the bromomethyl pyridine (IV).Lithiation of 1-methyl-2-(triethylsilyl)imidazole (V),followed by condensation with 4-cyanobenzaldehyde (VI),provides carbinol (VII).This is then condensed with bromide (IV) in the presence of Ag2O to give ether (VIII).5-Bromo-2,2-difluorobenzodioxole (IX) is lithiated with butyllithium in cold Et2O and subsequently treated with triisopropyl borate to afford,after aqueous work-up,the arylboronic acid (X).Finally,Mitsunobu coupling between boronic acid (X) and the bromopyridine (VIII) provides the title compound.
📌 参考资料/链接：
参考文献标题:Farnesyltransferase inhibitors
文献作者:Sham,H.L.; Rockway,T.W.; Li,T.; Mantei,R.A.; Li,Q.; Lin,N.-H.; Wang,L.; Wang,W.; Wang,X.; Sullivan,G.M.; Wang,G.T.; Gwaltney,S.L.II; Claiborne,A.K.; Hasvold,L.A.; Tong,Y.(Abbott Laboratories Inc.)
参考来源:US 2002115640; WO 0274747
📄 详细内容
合成路线:2-Bromo-3-methylpyridine (I) is converted to the corresponding N-oxide (II) by treatment with m-chloroperbenzoic acid in CH2Cl2.Reaction of N-oxide (II) with trimethylsilyl cyanide and dimethylcarbamoyl chloride gives rise to the 2-cyanopyridine (III).Subsequent radical bromination of (III) using NBS and AIBN affords the bromomethyl pyridine (IV).Lithiation of 1-methyl-2-(triethylsilyl)imidazole (V),followed by condensation with 4-cyanobenzaldehyde (VI),provides carbinol (VII).This is then condensed with bromide (IV) in the presence of Ag2O to give ether (VIII).5-Bromo-2,2-difluorobenzodioxole (IX) is lithiated with butyllithium in cold Et2O and subsequently treated with triisopropyl borate to afford,after aqueous work-up,the arylboronic acid (X).Finally,Mitsunobu coupling between boronic acid (X) and the bromopyridine (VIII) provides the title compound.
参考文献标题:Discovery of potent and orally active farnesyltransferase inhibitors
文献作者:Wang,L.; Hasvold,L.; Tong,Y.; et al.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 129
产品链接: CAS No. 450839-23-3››