Triethylamine → 6-[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylethynyl]-nicotinic acid methyl ester

HRID 402422Notes

Reaction equation

HRID 402422 reaction equation
[C:1]([C:3]1[N:7]([CH3:8])[N:6]=[N:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)#[CH:2].Br[C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][N:18]=1.C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:24][O:23][C:21](=[O:22])[C:20]1[CH:25]=[CH:26][C:17]([C:2]#[C:1][C:3]2[N:7]([CH3:8])[N:6]=[N:5][C:4]=2[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[N:18][CH:19]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 13349623Methyl 6-bromopyridine-3-carboxylateHCID 866647655-Ethynyl-4-(4-fluoro-phenyl)-1-methyl-1H-[1,2,3]triazole

Product 1

HCID 674980856-[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylethynyl]-nicotinic acid methyl esterYield 79.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-ethynyl-4-(4-fluoro-phenyl)-1-methyl-1H-[1,2,3]triazole (101 mg, 0.5 mmol), methyl 6-bromonicotinate (130 mg, 0.6 mmol), triethylamine (174 μL, 1.25 mmol) and PdCl2(PPh3)2 (11 mg, 0.3 mol %) in DMF (1 mL) was evaporated and flushed with Ar five times. Then CuI (2 mg, 0.2 mol %) was added and the reaction mixture was stirred at 90° C. for 30 min and DMF (1 mL) was added. The mixture was then poured into sodium hydroxide solution (1 M) 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 (133 mg, 79%) as a light yellow solid. MS: m/e=337.1 [M]+.

Workup

  1. customwas evaporated
  2. customflushed with Ar five times
  3. additionThen CuI (2 mg, 0.2 mol %) was added
  4. additionDMF (1 mL) was added
  5. additionThe mixture was then poured into sodium hydroxide solution (1 M)
  6. extractionextracted with ethyl acetate
  7. washthe combined organic extracts washed with brine
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customPurification by chromatography (silica, 0 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-f7b1890a1d8d4faaaebf925525a6ae37
Source dataset
uspto-grants-2014_06
Patent number
US08742097B2

Reaction notes

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