Sodium hydride → 3-Chloro-6-[3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazine

HRID 402447Notes

Reaction equation

HRID 402447 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([CH2:15][OH:16])=[C:13]([CH3:17])[N:12]=[N:11]2)=[CH:6][CH:5]=1.[Cl:18][C:19]1[N:20]=[N:21][C:22](Cl)=[CH:23][CH:24]=1>C1COCC1>[Cl:18][C:19]1[N:20]=[N:21][C:22]([O:16][CH2:15][C:14]2[N:10]([C:7]3[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=3)[N:11]=[N:12][C:13]=2[CH3:17])=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 673313,6-DichloropyridazineHCID 19914681(1-(4-Fluorophenyl)-4-methyl-1H-1,2,3-triazol-5-yl)methanol

Product 1

HCID 573356983-Chloro-6-[3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridazineYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (55%, 106 mg, 2.41 mmol) in THF (4 mL) a solution of [3-(4-fluoro-phenyl)-5-methyl-3H-[1,2,3]triazol-4-yl]-methanol (500 mg, 2.41 mmol) in THF (6 mL) was added under ice cooling. After the addition was complete the mixture was allowed to warm up to room temperature and stirred for 30 min. Again under ice cooling a solution of 3,6-dichloropyridazine (358 mg, 2.41 mmol) in THF (6 mL) was added and the reaction mixture 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) afforded the title compound (735 mg, 95%) as a colourless gun. MS: m/e=3020.1 [M+H]+.

Workup

  1. additionwas added under ice cooling
  2. additionAfter the addition
  3. stirringthe reaction mixture stirred at room temperature for 16 h
  4. extractionextracted with ethyl acetate
  5. washthe combined organic extracts washed with brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by chromatography (silica, 0 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-2c8356ea2bdd472aa9c5d24c1d40ebfc
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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