Sodium Sulfate → 5-Bromo-2-methyl-thiazole-4-carboxylic acid (5-fluoro-pyridin-2-yl)-amide

HRID 2244437Notes

Reaction equation

HRID 2244437 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C[Al](C)C.C[O:14][C:15]([C:17]1[N:18]=[C:19]([CH3:23])[S:20][C:21]=1[Br:22])=O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:15]([C:17]2[N:18]=[C:19]([CH3:23])[S:20][C:21]=2[Br:22])=[O:14])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 27377012-Amino-5-fluoropyridineHCID 16427155Methyl 5-bromo-2-methyl-1,3-thiazole-4-carboxylateHCID 16682925Trimethylaluminum

Product 1

HCID 866065715-Bromo-2-methyl-thiazole-4-carboxylic acid (5-fluoro-pyridin-2-yl)-amideYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 2-amino-5-fluoropyridine (6.0 g, 53 mmol) in 40 ml dry dioxane was treated at 0° C. with trimethylaluminium (2M in hexane, 26.8 ml, 53 mmol). The mixture was stirred at room temperature for 1 h. A solution of 5-bromo-2-methyl-thiazole-4-carboxylic acid methyl ester (4.2 g, 18 mmol) in 40 mL dry dioxane was added and the reaction mixture was refluxed for 4 h. 10 ml water and 10 g sodium sulfate were sequentially added and filtered. The filtrate was evaporated and the residue purified by flash chromatography (hetane, ethyl acetate) to yield 5-bromo-2-methyl-thiazole-4-carboxylic acid (5-fluoro-pyridin-2-yl)-amide (3.0 g, 53%) as a white solid, MS (ISP): m/e=318.0 (M+H+).

Workup

  1. temperaturethe reaction mixture was refluxed for 4 h
  2. filtrationfiltered
  3. customThe filtrate was evaporated
  4. customthe residue purified by flash chromatography (hetane, ethyl acetate)

Sources & evidence

ORD record
ord-1c37840545ed4f7797c6ebbb47025eec
Source dataset
uspto-grants-2010_03
Patent number
US07678815B2

Reaction notes

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