Cesium carbonate → 5-(5-Fluoro-pyridin-3-ylamino)-2-methyl-thiazole-4-carboxylic acid (2-methyl-pyridin-4-yl)-amide

HRID 2244448Notes

Reaction equation

HRID 2244448 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]=[C:13]([CH3:17])[S:14][C:15]=2[NH2:16])=[O:10])[CH:5]=[CH:4][N:3]=1.[F:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23](F)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]=[C:13]([CH3:17])[S:14][C:15]=2[NH:16][C:23]2[CH:22]=[N:21][CH:20]=[C:19]([F:18])[CH:24]=2)=[O:10])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 6428203,5-DifluoropyridineHCID 866065745-Amino-2-methyl-thiazole-4-carboxylic acid (2-methyl-pyridin-4-yl)-amide

Product 1

HCID 116958495-(5-Fluoro-pyridin-3-ylamino)-2-methyl-thiazole-4-carboxylic acid (2-methyl-pyridin-4-yl)-amideYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Amino-2-methyl-thiazole-4-carboxylic acid (2-methyl-pyridin-4-yl)-amide (0.15 g, 0.605 mmol) was dissolved in 5 mL fry DMF. 3,5-Difluoropyridine (0.213 g, 1.85 mmol) and cesium carbonate (0.59 g, 1.85 mmol) were added. The reaction mixture was irradiated in the microwave at 150° C. for 45 min, diluted with 100 mL water and extracted three times with ethyl acetate (50 mL each). The organic phases were pooled, dried with sodium sulfate and evaporated. The crude product was flash-chromatographed on silica gel with heptane/ethyl acetate 100:0→0:100 gradient to yield the title compound as an off-white solid (0.135 g, 65%), MS (ISP): m/e=344.1 (M+H+).

Workup

  1. customThe reaction mixture was irradiated in the microwave at 150° C. for 45 min
  2. extractionextracted three times with ethyl acetate (50 mL each)
  3. dry with materialdried with sodium sulfate
  4. customevaporated
  5. customThe crude product was flash-chromatographed on silica gel with heptane/ethyl acetate 100:0→0:100 gradient

Sources & evidence

ORD record
ord-2ca27fa780244fc4827b0181fa48c126
Source dataset
uspto-grants-2010_03
Patent number
US07678815B2

Reaction notes

Loading…