Sodium Carbonate → 4-(2-Methylpyridin-3-yl)-6-tert-butylpyrimidine

HRID 2275977Notes

Reaction equation

HRID 2275977 reaction equation
[C:1]([C:5]1[CH:10]=[C:9](Cl)[N:8]=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:12][C:13]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=[CH:15][N:14]=1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.CCCCCC.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.C(#N)C>[CH3:12][C:13]1[C:18]([C:9]2[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[N:6]=[CH:7][N:8]=2)=[CH:17][CH:16]=[CH:15][N:14]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 42892434-Chloro-6-(1,1-dimethylethyl)pyrimidineHCID 164142712-Methylpyridine-3-boronic acid, pinacol ester

Product 1

HCID 712695924-(2-Methylpyridin-3-yl)-6-tert-butylpyrimidineYield 92%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolventHCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

Next, 2.0 g of 4-tert-butyl-6-chloropyrimidine obtained in Step 2, 3.0 g of 2-methylpyridine-3-boronic acid pinacol ester, 17 mL of a 1M aqueous solution of potassium acetate, 17 mL of a 1M aqueous solution of sodium carbonate, and 40 mL of acetonitrile were put in a 100-mL round-bottom flask, and the air in the flask was replaced with argon. To this mixture, 0.78 g of tetrakis(triphenylphosphine)palladium(0) was added, and the mixture was irradiated with microwaves under conditions of 100° C. and 100 W for 1 hour to cause a reaction. This reaction mixture was subjected to extraction with ethyl acetate, and washing with a saturated aqueous solution of sodium chloride was performed. Anhydrous magnesium sulfate was added to the obtained solution of the extract for drying, and the resulting mixture was gravity-filtered to give a filtrate. The resulting filtrate was dissolved in a mixed solvent of ethyl acetate and hexane, and the mixture was filtered through Celite, alumina, and Celite. The resulting filtrate was purified by silica gel column chromatography. As a developing solvent, a mixed solvent of hexane and ethyl acetate in a ratio of 3:2 (v/v) was used. The obtained fraction was condensed to give an oily substance. This oily substance was dissolved in a mixed solvent of hexane and ethyl acetate, and the solution was filtered through a filter aid in which Celite, alumina, and Celite were stacked in this order. The resulting filtrate was condensed to give HtBumpypm (light-yellow oily substance, yield of 92%). Synthesis Scheme (b-3) of Step 3 is shown below.

Workup

  1. customthe mixture was irradiated with microwaves under conditions of 100° C. and 100 W for 1 hour
  2. customa reaction
  3. extractionThis reaction mixture was subjected to extraction with ethyl acetate
  4. washwashing with a saturated aqueous solution of sodium chloride
  5. additionAnhydrous magnesium sulfate was added to the obtained solution of the
  6. extractionextract
  7. customfor drying
  8. filtrationthe resulting mixture was gravity-filtered
  9. customto give a filtrate
  10. filtrationthe mixture was filtered through Celite, alumina, and Celite
  11. customThe resulting filtrate was purified by silica gel column chromatography
  12. customcondensed
  13. customto give an oily substance
  14. filtrationthe solution was filtered through a filter aid in which Celite, alumina, and Celite
  15. customcondensed
  16. customto give HtBumpypm (light-yellow oily substance, yield of 92%)
  17. customSynthesis Scheme (b-3) of Step 3

Sources & evidence

ORD record
ord-5bcd5dc6d5544f84aed3f9bb96f44b3c
Source dataset
uspto-grants-2015_09
Patent number
US09130182B2

Reaction notes

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