1H-1,2,4-Triazole → Letrozole

HRID 495063

Reaction equation

HRID 495063 reaction equation
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

Participants

6

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 869964-(Bromomethyl)benzonitrileHCID 178509721HCID 178509721, compound

Product 1

HCID 3902Letrozole

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

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.

Workup

  1. customThe intermediate is purified by chromatography on silica gel
  2. washeluting with chloroform and isopropanol
  3. customreacted with 4-fluorobenzonitrile and potassium tert-butoxide in DMF

Sources & evidence

ORD record
ord-92b45117926b4c25a1e347776e8925a1
Source dataset
uspto-grants-2009_05
Patent number
US07538230B2

Linked notes

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