1H-1,2,4-Triazole → Letrozole

反応式

N1C=N[C:3]([CH2:6][C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)=N1.BrCC1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1.[NH:25]1[CH:29]=[N:28][CH:27]=[N:26]1>C(#N)C.C(Cl)(Cl)Cl>[CH:13]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]([CH:6]([N:25]2[N:26]=[CH:27][N:28]=[CH:29]2)[C:3]2[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][CH:22]=2)[CH:14]=1

参加物

実験手順

U.S. Pat. No. 5,473,078 (“the '078 patent”) describes a method of preparing 4-[1-(1,2,4-triazolyl)methyl]benzonitrile by refluxing a solution of α-bromo-4-tolunitrile with 1,2,4-triazole for 15 hours in a mixture of acetonitrile and chloroform. The intermediate is purified by chromatography on silica gel, eluting with chloroform and isopropanol, and then reacted with 4-fluorobenzonitrile and potassium tert-butoxide in DMF, to obtain letrozole. An exemplary process described in the '078 patent is generally depicted in Scheme 1.