新产品编号:864281

Chemical Name: 7-[2-Chloro-4-(difluoromethoxy)phenyl]-3-(1-cyclobutylethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine
CAS No. 345226-13-3
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Nitration of 2,4-dihydroxypyridine (I) affords the 3-nitro derivative (II).Selective chlorination of the 4-hydroxy group of (II) is accomplished by treatment of the cycloheptylamine salt of (II) with POCl3 to furnish 4-chloro-2-hydroxy-3-nitropyridine (III).The 2-hydroxy group of (III) is then protected as the benzyl ether (IV) using benzyl bromide in the presence of silver carbonate.Suzuki coupling of protected chloropyridine (IV) with 2-chloro-4-(difluoromethoxy)phenylboronic acid (V) leads to the phenylpyridine derivative (VI).The O-benzyl group of (VI) is then removed with trifluoroacetic acid,and the resultant 2-hydroxypyridine (VII) is further chlorinated by means of POCl3,yielding (VIII).Displacement of the 2-chloro substituent of (VIII) with 1-cyclobutylethylamine (IX) in refluxing acetonitrile furnishes the 2-amino-3-nitropyridine (X).Subsequent nitro group reduction in (X) employing sodium dithionite and ammonium hydroxide leads to diamine (XI).This is finally cyclized to the desired imidazopyridine upon heating at reflux with propionic acid.