Diisopropylethylamine → 5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylthio)-1H-pyrazol-1-yl)benzonitrile

HRID 576806

Reaction equation

HRID 576806 reaction equation
[CH2:1]([N:3]1[C:8](=[O:9])[C:7]([C:10]2[N:14](C3C=CC(C#N)=CC=3)[N:13]=[CH:12][C:11]=2I)=[C:6]([CH3:24])[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)[C:4]1=[O:35])C.C([N:39]([CH2:43][CH3:44])C(C)C)(C)C.[CH3:45][S-:46].[Na+]>CN(C)C=O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:1][N:3]1[C:8](=[O:9])[C:7]([C:10]2[C:11]([S:46][CH3:45])=[CH:12][N:13]([C:6]3[CH:7]=[CH:10][CH:11]=[C:44]([CH:24]=3)[C:43]#[N:39])[N:14]=2)=[C:6]([CH3:24])[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:34])[F:33])[CH:26]=2)[C:4]1=[O:35]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 4378561Sodium methanethiolateHCID 86723911HCID 86723911, compound

Product 1

HCID 867239105-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylthio)-1H-pyrazol-1-yl)benzonitrile

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-(5-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-iodo-1H-pyrazol-1-yl)benzonitrile (prepared in Example 268) (98.1 mg) in N,N-dimethy formamide (1.0 ml) were added palladium dibenzylidene acetone complex (15.9 mg), 1,1′-bis(diphenylphosphino)ferrocene) (18.9 mg), N,N-diisopropylethylamine (33.8 μl) and sodium methanethiolate (13.4 mg) and the resulting mixture was stirred at 110° C. for four hours. The reaction mixture was diluted with ethyl acetate (50 ml) and washed with saturated saline (20 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylthio)-1H-pyrazol-1-yl)benzonitrile (57.4 mg).

Workup

  1. washwashed with saturated saline (20 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: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b496b463bad3458ea4b2e23b82d8ca29
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Linked notes

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