Water → HCID 86723904, compound

HRID 576793Notes

Reaction equation

HRID 576793 reaction equation
C([O:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=3)[N:17]=[CH:16][C:15]=2Br)=[C:10]([CH3:28])[N:9]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=2)[C:8]1=[O:39])(=O)C.[C:40](B1OC(C)(C)C(C)(C)O1)([CH3:42])=[CH2:41].C(=O)([O-])[O-].[Na+].[Na+].O>C(COC)OC.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(OCC)(=O)C>[OH:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=3)[N:17]=[CH:16][C:15]=2[CH:40]([CH3:42])[CH3:41])=[C:10]([CH3:28])[N:9]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:38])[F:36])[CH:30]=2)[C:8]1=[O:39]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 86723905HCID 86723905, compound

Product 1

HCID 86723904HCID 86723904, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(5-(4-bromo-1-(4-cyanophenyl)-1H-pyrazol-5-yl)-4-methyl-2,6-dioxo-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl)ethyl acetate (prepared in Example 98) (220.3 mg) in dimethoxyethane (4.0 ml) were added isopropenyl boronic acid pinacol ester (69.0 μl), tetrakis(triphenylphosphine)palladium (85.2 mg), sodium carbonate (194.3 mg) and water (0.4 ml) and the resulting mixture was stirred at 100° C. for seven hours. To the reaction mixture was added ethyl acetate (100 ml) and the mixture was washed with water (30 ml) and saturated saline (30 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. To a solution of the residue in methanol (4 ml) was added palladium carbon (28.7 mg) and the resulting mixture was stirred at room temperature under hydrogen atmosphere for six hours. The reaction mixture was filtered through Celite (trade mark) and then concentrated under reduced pressure. To a solution of the residue in methanol (5 ml) was added under ice-cooling 1M aqueous potassium carbonate solution (392 μl) and the resulting mixture was stirred under ice-cooling for one hour. To the reaction mixture was added 1M hydrochloric acid (329 μl) and the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate) to afford 4-(5-(3-(2-hydroxyethyl)-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-isopropyl-1H-pyrazol-1-yl)benzonitrile (62.6 mg) as white solid.

Workup

  1. washthe mixture was washed with water (30 ml) and saturated saline (30 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionTo a solution of the residue in methanol (4 ml) was added palladium carbon (28.7 mg)
  5. stirringthe resulting mixture was stirred at room temperature under hydrogen atmosphere for six hours
  6. filtrationThe reaction mixture was filtered through Celite (trade mark)
  7. concentrationconcentrated under reduced pressure
  8. additionTo a solution of the residue in methanol (5 ml) was added under ice-
  9. temperaturecooling 1M aqueous potassium carbonate solution (392 μl)
  10. stirringthe resulting mixture was stirred under ice-
  11. temperaturecooling for one hour
  12. additionTo the reaction mixture was added 1M hydrochloric acid (329 μl)
  13. concentrationthe mixture was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate)

Sources & evidence

ORD record
ord-0a2f6243eb2d455497dd93a70d5359af
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

Loading…