Potassium Carbonate → 2-[1-(4-chloro-benzyl)-1H-pyrazol-3-yl]-4-methyl-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)amide

HRID 1879183Notes

Reaction equation

HRID 1879183 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]([C:16]3[NH:17][N:18]=[CH:19][CH:20]=3)=[N:13][C:12]=2[CH3:21])=[O:10])[CH:2]=1.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(OCC)(=O)C>[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:16]3[CH:20]=[CH:19][N:18]([CH2:27][C:26]4[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=4)[N:17]=3)=[N:13][C:12]=2[CH3:21])=[O:10])[CH:2]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 866455594-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)-amide

Product 1

HCID 249568522-[1-(4-chloro-benzyl)-1H-pyrazol-3-yl]-4-methyl-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)amideYield 51%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)-amide (0.2 g, 0.67 mmol) in dimethyl sulfoxide (5 mL) was added with 4-chlorobenzyl bromide (0.14 g, 0.67 mmol) and potassium carbonate (0.30 g, 2.0 mmol). The reaction mixture was heated to 90° C. for 16 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), and washed with brine (2×50 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by preparative thin layer chromatography over silica gel (methylene chloride:methanol, 95:5) to provide 2-[1-(4-chloro-benzyl)-1H-pyrazol-3-yl]-4-methyl-thiazole-5-carboxylic acid (pyridin-3-ylmethyl)amide as a white solid (0.071 g, 51% yield). 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 8.54-8.56 (m, 1H), 7.71 (d, J=8 Hz, 1H), 7.39 (s, 1H) 7.26-7.33 (m, 3H), 7.18 (d, J=4 Hz, 2H), 6.84 (d, J=4 Hz, 1H), 6.18-6.21 (m, 1H), 5.31 (s, 2H), 4.62 (d, J=4 Hz, 2H), 2.74 (s, 3H). MS (M+H)+=423.9; Rt=1.29 min; HRMS (M+H)+=424.10.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with brine (2×50 mL)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated
  5. customThe residue was purified by preparative thin layer chromatography over silica gel (methylene chloride:methanol, 95:5)

Sources & evidence

ORD record
ord-08f95e251907480fad3d8526525b3257
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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