1H-1,2,4-Triazole → Anastrozole

HRID 2107763Notes

Reaction equation

HRID 2107763 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-methylpropiononitrile), 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-2396888915c847f4b9d53ce08f1c5b9d
Source dataset
uspto-grants-1990_06
Patent number
US04935437

Reaction notes

Loading…