1H-1,2,4-Triazole → Anastrozole

HRID 1636801Notes

Reaction equation

HRID 1636801 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH:6]=[C:7]([C:9]([CH3:13])([CH3:12])[C:10]#[N:11])[CH:8]=1.[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1>C(#N)C>[N:19]1([CH2:2][C:3]2[CH:4]=[C:5]([C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH:6]=[C:7]([C:9]([CH3:13])([CH3:12])[C:10]#[N:11])[CH:8]=2)[CH:23]=[N:22][CH:21]=[N:20]1

Participants

4

Reactant 2

HCID 92571H-1,2,4-TriazoleHCID 193493842-(3-(Chloromethyl)-5-(2-cyanopropan-2-yl)phenyl)-2-methylpropanenitrile

Product 1

HCID 2187Anastrozole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,2'-(5-chloromethyl-1,3-phenylene)di(2-methylpropiononitrile), (0.23 g), and 1H-1,2,4-triazole (0.35 g) in acetonitrile (2 ml) was heated under reflux for 18 h, then evaporated to dryness. The residue was partitioned between 1N aqueous potassium hydrogen carbonate solution and ethyl acetate, the organic phase was separated, dried and evaporated to dryness under reduced pressure, and the residue was purified by flash column chromatography. Elution with methanol:chloroform (1:49 by volume), gave 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]di(2-methylpropiononitrile), identical with the product of Example 1, and further elution with methanol:chloroform (2:23 by volume, gave 2,2'-[5-(4H-1,2,4-triazol-4-ylmethyl)-1,3-phenylene]di(2-methylpropiononit rile), mp. 158°-161°.

Workup

  1. temperatureunder reflux for 18 h
  2. customevaporated to dryness
  3. customThe residue was partitioned between 1N aqueous potassium hydrogen carbonate solution and ethyl acetate
  4. customthe organic phase was separated
  5. customdried
  6. customevaporated to dryness under reduced pressure
  7. customthe residue was purified by flash column chromatography
  8. washElution with methanol:chloroform (1:49 by volume)

Sources & evidence

ORD record
ord-4a04191071ee4e03bd6934d6f4e663b5
Source dataset
uspto-grants-2000_03
Patent number
USRE036617

Reaction notes

Loading…