Sodium Carbonate → HCID 86723867, compound

HRID 576753Notes

Reaction equation

HRID 576753 reaction equation
I[C:2]1[C:3](=[O:23])[N:4]([CH:20]([CH3:22])[CH3:21])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].[Br:24][C:25]1[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=[CH:27][N:26]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.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.O>[Br:24][C:25]1[C:30]([C:2]2[C:3](=[O:23])[N:4]([CH:20]([CH3:22])[CH3:21])[C:5](=[O:19])[N:6]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=3)[C:7]=2[CH3:8])=[CH:29][CH:28]=[CH:27][N:26]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 120670612-Bromo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90197008HCID 90197008, compound

Product 1

HCID 86723867HCID 86723867, compoundYield 20.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-Iodo-3-isopropyl-6-methyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 85) (600 mg) and 2-bromo-3-pyridine boronic acid pinacol ester (878 mg) were dissolved in 1,2-dimethoxyethane (30 ml). Thereto were added under nitrogen atmosphere water (6 ml), sodium carbonate (290 mg), 2-(dicyclohexylphosphino)biphenyl (57.6 mg) and tetrakis(triphenylphosphine)palladium (316 mg) and the resulting mixture was stirred with heating under reflux for four and a half hours. The reaction solution was concentrated under reduced pressure and to the residue was added water, and the resulting mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with saturated saline (50 ml), dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 5-(2-bromopyridin-3-yl)-3-isopropyl-6-methyl-1-(3-(trifluoromethyl)phenyl)pyrimidin-2,4(1H,3H)-dione (134 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for four and a half hours
  3. concentrationThe reaction solution was concentrated under reduced pressure and to the residue
  4. additionwas added water
  5. extractionthe resulting mixture was extracted with ethyl acetate (50 ml)
  6. washThe organic layer was washed with saturated saline (50 ml)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a3ef9d94cb2e4c5a89fb053494a3ad3e
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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