Potassium Carbonate → 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)-amide

HRID 1879182Notes

Reaction equation

HRID 1879182 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[S:15][C:14](Br)=[N:13][C:12]=2[CH3:17])=[O:10])[CH:2]=1.[NH:18]1[C:22](B(O)O)=[CH:21][CH:20]=[N:19]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[S:15][C:14]([C:22]3[NH:18][N:19]=[CH:20][CH:21]=3)=[N:13][C:12]=2[CH3:17])=[O:10])[CH:2]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 112519791H-Pyrazole-5-boronic acidHCID 666315502-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

Product 1

HCID 866455594-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)-amideYield 87.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (pyridine-3-ylmethyl)-amide (5.0 g, 16.0 mmol) in toluene (30 mL), water (10 mL) and ethanol (10 mL) was added 1H-pyrazole-5-boronic acid (2.15 g, 19.2 mmol), Pd(PPh3)4 (1.85 g, 1.60 mmol), and potassium carbonate (6.64 g, 48.1 mmol). The resulting mixture was degassed three times and heated to 100° C. for 16 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and washed with brine (2×100 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was recrystallized from ethyl acetate to provide 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridine-3-ylmethyl)amide as a white solid (4.20 g, 85% yield).

Workup

  1. customThe resulting mixture was degassed three times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (200 mL)
  4. washwashed with brine (2×100 mL)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated
  7. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-3966c43517204587a50726a828dfdcfa
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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