Dimethylcarbamoyl Chloride → 2-(2,4-difluorophenyl)-3-(6-cyanopyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

HRID 2380064Notes

Reaction equation

HRID 2380064 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([CH:16]([C:18]1[CH:23]=[CH:22][N+:21]([O-])=[CH:20][N:19]=1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[CH3:26][N:27](C)C(Cl)=O.C[Si](C#N)(C)C>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([CH:16]([C:18]1[CH:23]=[C:22]([C:26]#[N:27])[N:21]=[CH:20][N:19]=1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 82115Trimethylsilyl cyanideHCID 189565212-(2,4-Difluorophenyl)-3-(1-oxidopyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Product 1

HCID 189565472-(2,4-difluorophenyl)-3-(6-cyanopyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-olYield 3.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of the product of part (i) (0.80 g) and N,N-dimethylcarbamoyl chloride (0.50 g) in dichloromethane (10 ml) was stirred at room temperature for 2 hours. Trimethylsilyl cyanide (0.50 g) was added and stirring was continued for a further 6 days. The solution was evaporated and the residue was chromatographed on silica gel. Elution with dichloromethane/methanol (100:1) gave a product which was rechromatographed on silica gel. Elution was commenced with ether and the polarity of the eluant was gradually increased by the addition of up to 6% (by volume) of methanol. Combination and evaporation of the initial product-containing fractions gave 2-(2,4-difluorophenyl)-3-(6-cyanopyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (30 mg), m.p. 148°-149°.

Workup

  1. stirringstirring
  2. waitwas continued for a further 6 days
  3. customThe solution was evaporated
  4. customthe residue was chromatographed on silica gel
  5. washElution with dichloromethane/methanol (100:1)
  6. customgave a product which
  7. customwas rechromatographed on silica gel
  8. washElution
  9. temperaturethe polarity of the eluant was gradually increased by the addition of up to 6% (by volume) of methanol
  10. customCombination and evaporation of the
  11. additioninitial product-containing fractions

Sources & evidence

ORD record
ord-64662918c5bf48d1a2cc18ff0ca95c1c
Source dataset
uspto-grants-1994_11
Patent number
US05364938

Reaction notes

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