Potassium Carbonate → methyl 4-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxylate

HRID 60136

Reaction equation

HRID 60136 reaction equation
CC1(C)C(C)(C)OBO1.Br[C:11]1[CH:12]=[N:13][N:14]([CH3:20])[C:15]=1[C:16]([O:18][CH3:19])=[O:17].C(=O)([O-])[O-].[K+].[K+].Cl[C:28]1[C:33]([CH3:34])=[CH:32][N:31]=[C:30]([CH3:35])[N:29]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O.O1CCOCC1.C(N(CC)CC)C>[CH3:35][C:30]1[N:31]=[C:32]([C:11]2[CH:12]=[N:13][N:14]([CH3:20])[C:15]=2[C:16]([O:18][CH3:19])=[O:17])[C:33]([CH3:34])=[CH:28][N:29]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 673643Methyl 4-bromo-1-methyl-1H-pyrazole-5-carboxylateHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolane2×HCID 124653814-Chloro-2,5-dimethylpyrimidine

Product 1

HCID 90383435methyl 4-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxylateYield 110%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

4,4,5,5-Tetramethyl-1,3,2-dioxaborolane (1.5 ml) was added to a 1,4-dioxane (19 ml) solution of methyl 4-bromo-1-methyl-1H-pyrazole-5-carboxylate (1.9 g), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.15 g), Tris(dibenzylideneacetone)dipalladium(0) (0.16 g), and triethylamine (3.7 ml). The obtained mixture was stirred in a nitrogen atmosphere at 100° C. for 30 minutes. Thereafter, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 ml) was added to the reaction solution, and the obtained mixture was then stirred for 30 minutes at the same temperature as described above. Thereafter, an aqueous solution (3.9 ml) of potassium carbonate (3.6 g) and a 1,4-dioxane (4 ml) solution of 4-chloro-2,5-dimethylpyrimidine (1.0 g) were successively added to the reaction solution, and the obtained mixture was then stirred at the same temperature as described above for 1 hour. Thereafter, water was added to the reaction solution, and the mixed solution was extracted with ethyl acetate and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the obtained residue was purified by silica gel column chromatography (silica gel:eluent; heptane:ethyl acetate=3:1-1:1-0:1), so as to obtain the title compound (1.9 g) in the form of an orange liquid.

Workup

  1. stirringthe obtained mixture was then stirred for 30 minutes at the same temperature
  2. stirringthe obtained mixture was then stirred at the same temperature
  3. customas described above for 1 hour
  4. extractionthe mixed solution was extracted with ethyl acetate
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled away under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (silica gel:eluent; heptane:ethyl acetate=3:1-1:1-0:1)

Sources & evidence

ORD record
ord-703c64c185294d3fb38394e58541bf0b
Source dataset
uspto-grants-2016_09
Patent number
US09440970B2

Linked notes

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