Sodium hydride → 5-[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyrazine-2-carboxylic acid methyl ester

HRID 402411Notes

Reaction equation

HRID 402411 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[N:13][N:12]([CH3:15])[C:11]=2[CH2:16][OH:17])=[CH:6][CH:5]=1.Cl[C:19]1[N:20]=[CH:21][C:22]([C:25]([O:27][CH3:28])=[O:26])=[N:23][CH:24]=1>C1COCC1>[CH3:28][O:27][C:25]([C:22]1[CH:21]=[N:20][C:19]([O:17][CH2:16][C:11]2[N:12]([CH3:15])[N:13]=[N:14][C:10]=2[C:7]2[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=2)=[CH:24][N:23]=1)=[O:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 67498408[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-methanol

Product 1

HCID 674979845-[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyrazine-2-carboxylic acid methyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaH (55% in oil, 131 mg, 3.0 mmol) in THF (3.9 mL) was added a solution of [5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-methanol (622 mg, 3.0 mmol) in THF (7.9 mL) dropwise at 0° C. and the reaction mixture was stirred at room temperature for 30 min. Then a solution of methyl 5-chloropyrazine-2-carboxylate (569 mg, 3.3 mmol) in THF (7.9 mL) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature for 16 h. The mixture was then poured into ice water and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, 0 to 50% ethyl acetate in heptane, then 0 to 5% methanol in dichloromethane) afforded the title compound (474 mg, 46%) as an off white gum. MS: m/e=344.1 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 h
  2. extractionextracted with ethyl acetate
  3. washthe combined organic extracts washed with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (silica, 0 to 50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-00990e8e39004a8dbd4952dc410fd3c6
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

Loading…