Potassium Carbonate → HCID 58513684, compound

HRID 469174Notes

Reaction equation

HRID 469174 reaction equation
CC1C=C(N[C:10]2[N:15]=[C:14]([N:16]3[CH:20]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:18]([CH3:26])=[N:17]3)[CH:13]=[CH:12][N:11]=2)C=C(C)C=1.C(=O)([O-])[O-].[K+].[K+].ClC1C=CN=[C:36]([S:40]C)N=1>C(#N)C.C(OCC)(=O)C>[CH3:26][C:18]1[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:20][N:16]([C:14]2[CH:13]=[CH:12][N:11]=[C:10]([S:40][CH3:36])[N:15]=2)[N:17]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 971134-Chloro-2-methylthiopyrimidineHCID 53233533HCID 53233533, compound

Product 1

HCID 58513684HCID 58513684, compoundYield 707.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 3-methyl-1H-pyrazole-4-carboxylate 2 (5.0 g, 32 4 mmol) in anhydrous acetonitrile (60 mL) were added potassium carbonate (8.96 g, 64.9 mmol) and 4-chloro-2-(methylthio)pyrimidine 11 (5.47 g, 34.1 mmol) at room temperature (rt). The resulting suspension was heated at 80° C. for 8 hours with monitoring a reaction with LC-MS or thin layer chromatography (TLC). It was diluted with ethyl acetate and washed with brine. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacou. The resulting residue was recrystallized with methanol to give 7.88 g (83%) of ethyl 3-methyl-1-(2-(methylthio)pyrimidin-4-yl)-1H-pyrazole-4-carboxylate 12; MS (ESI) m/z 279 [M+H]+. The resulting pyrazole-4-carboxylate 12 (7.44 g, 26 7 mmol) was dissolved in 30 mL of DCM and then cooled to 0° C. To this was added 3-chloroperbenzoic acid (mCPBA, 13.2 g, 58.8 mmol) at the same temperature. The reaction was warmed to room temperature, stirred for 2 hours and then quenched by addition of saturated NaHCO3 solution. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacou. The resulting residue was recrystallized with iso-propylether to give 7.88 g (83%) of ethyl 3-methyl-1-(2-(methylsulfonyl)pyrimidin-4-yl)-1H-pyrazole-4-carboxylate 13 as a colorless solid (6.92 g, 83%); m/z 311 [M+H]+. The obtained sulfoxide 13 (3.0 g, 9.7 mmol) was mixed with acetic acid (0.42 mL, 9.7 mmol) and 3,5-dimethylaniline (1.4 mL, 9.7 mmol) in 10 mL of n-butanol. After being heated at reflux for 2 hours, the mixture was concentrated in vacou. The resulting residue was extracted with DCM, washed with a saturated NaHCO3 solution. The collected organic layer was dried over anhydrous sodium sulfate, concentrated in vacou and then recrystallized with ethyl acetate to afford 0.86 g (26%) of Compound No. 2 as a pale yellow solid; m/z 352 [M+H]+.

Workup

  1. customa reaction with LC-MS or thin layer chromatography (TLC)
  2. washwashed with brine
  3. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacou
  5. customThe resulting residue was recrystallized with methanol

Sources & evidence

ORD record
ord-2a542a0e40984a4390f74bb76f71d0d4
Source dataset
uspto-grants-2014_01
Patent number
US08629132B2

Reaction notes

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