Water → HCID 86723866, compound

HRID 576765Notes

Reaction equation

HRID 576765 reaction equation
Br[C:2]1[C:7]([C:8]2[C:9](=[O:29])[N:10]([CH:26]([CH3:28])[CH3:27])[C:11](=[O:25])[N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[C:13]=2[CH3:14])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)#[N:31].O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[CH:26]([N:10]1[C:9](=[O:29])[C:8]([C:7]2[C:2]([C:35]3[CH:36]=[CH:37][C:32]([C:30]#[N:31])=[CH:33][CH:34]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)=[C:13]([CH3:14])[N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:11]1=[O:25])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 86723867HCID 86723867, compound

Product 1

HCID 86723866HCID 86723866, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

5-(2-Bromopyridin-3-yl)-3-isopropyl-6-methyl-1-(3-(trifluoromethyl)phenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 189) (132 mg) and 4-cyanophenylboronic acid (166 mg) were dissolved in 1,4-dioxane (10 ml). Thereto were added under nitrogen atmosphere water (1 ml), sodium carbonate (239 mg) and tetrakis(triphenylphosphine)palladium (33 mg) and the resulting mixture was stirred with heating under reflux for one and a half hours. The reaction mixture was cooled to room temperature, and thereto was then 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: firstly hexane/ethyl acetate, secondly chloroform/methanol) to afford 4-(3-(3-isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)pyridin-2-yl)benzonitrile (118 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for one and a half hours
  3. extractionwater and the resulting mixture was extracted with ethyl acetate (50 ml)
  4. washThe organic layer was washed with saturated saline (50 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-c9e1958f44764cdfa67082e742db7d4d
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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