Water → 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylic acid

HRID 576788Notes

Reaction equation

HRID 576788 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=2)[C:6]=1[C:7]1[C:8](=[O:26])[N:9]([CH3:25])[C:10](=[O:24])[N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[C:12]=1[CH3:13].C(N(CC)C(C)C)(C)C.O.[C:45]([O:48]CC)(=[O:47])C>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>[C:31]([C:30]1[CH:33]=[CH:34][C:27]([N:5]2[C:6]([C:7]3[C:8](=[O:26])[N:9]([CH3:25])[C:10](=[O:24])[N:11]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=4)[C:12]=3[CH3:13])=[C:2]([C:45]([OH:48])=[O:47])[CH:3]=[N:4]2)=[CH:28][CH:29]=1)#[N:32]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 867238984-(4-bromo-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile

Product 1

HCID 712514111-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-(4-bromo-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (prepared in Example 93) (139.8 mg) in 1,4-dioxane (2.0 ml) were added tetrakis(triphenylphosphine)palladium (30.7 mg),N,N-diisopropylethylamine (46.8 μl) and water (0.5 ml) and the resulting mixture was stirred at 100° C. under carbon monoxide atmosphere for four hours. To the reaction mixture was added ethyl acetate (100 ml) and the mixture was washed with 1M hydrochloric acid (30 ml) and saturated saline (30 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol) to afford 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylic acid (24.5 mg) as brown solid.

Workup

  1. washthe mixture was washed with 1M hydrochloric acid (30 ml) and saturated saline (30 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol)

Sources & evidence

ORD record
ord-d5f56c7cd84d47b08ccc3144ce9eb0cf
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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