Hydrochloric Acid → HCID 21712157, compound

HRID 650496Notes

Reaction equation

HRID 650496 reaction equation
[Cl:1][C:2]1[C:3]([OH:18])=[N:4][C:5]([C:9]2[C:13]([CH3:14])=[C:12]([C:15]#[N:16])[N:11]([CH3:17])[N:10]=2)=[C:6]([F:8])[CH:7]=1.[Br-].[Li+].[H-].[Na+].[CH3:23]I.Cl>CN(C)C=O.COCCOC>[Cl:1][C:2]1[C:3](=[O:18])[N:4]([CH3:23])[C:5]([C:9]2[C:13]([CH3:14])=[C:12]([C:15]#[N:16])[N:11]([CH3:17])[N:10]=2)=[C:6]([F:8])[CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 178422336HCID 178422336, compound

Product 1

HCID 21712157HCID 21712157, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
22 °C

Procedure

1.54 g of 3-chloro-6-(1,4-dimethyl-5-cyano-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol are introduced into a mixture of 20 ml of absolute 1,2-dimethoxyethane and 5 ml of absolute dimethylformamide at 22° C. With stirring, first 1.20 g of lithium bromide are added and then, 10 minutes later, in portions, 0.28 g of a 60% sodium hydride dispersion in oil. After a further 10 minutes, 0.86 ml of methyl iodide is added, after which the mixture is stirred overnight at 90° C. The mixture is then cooled to 22° C., carefully poured into dilute hydrochloric acid, and extracted with diethyl ether. The combined ethereal phases are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo together with 4 g of silica gel. The silica gel is applied to a flash chromatography column and fractionated by means of gradient elution using n-hexane/ethyl acetate 3/1 to 1/1 (v/v). 0.68 g of the desired compound is obtained in the form of a white solid having a melting point of 190-191° C.

Workup

  1. custom10 minutes
  2. stirringafter which the mixture is stirred overnight at 90° C
  3. extractionextracted with diethyl ether
  4. washThe combined ethereal phases are washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo together with 4 g of silica gel
  8. washfractionated by means of gradient elution

Sources & evidence

ORD record
ord-064da8c2cb7b4a06861ae3361041b756
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Reaction notes

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