Acetic Acid → 4-[4-[6-methyl-2,4-dioxo-3-propyl-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-4H-1,2,4-triazol-3-yl]benzonitrile

HRID 576766Notes

Reaction equation

HRID 576766 reaction equation
[C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([NH:9][NH2:10])=O)=[CH:5][CH:4]=1)#[N:2].[CH3:13]OC(OC)N(C)C.[NH2:21][C:22]1[C:23](=[O:43])[N:24]([CH2:40][CH2:41][CH3:42])[C:25](=[O:39])[N:26]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=2)[C:27]=1[CH3:28].C(O)(=O)C>CN(C)C=O.O>[CH3:28][C:27]1[N:26]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:36])[F:38])[CH:30]=2)[C:25](=[O:39])[N:24]([CH2:40][CH2:41][CH3:42])[C:23](=[O:43])[C:22]=1[N:21]1[CH:13]=[N:10][N:9]=[C:7]1[C:6]1[CH:11]=[CH:12][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 78373Dimethylformamide dimethyl acetalHCID 4567324-CyanobenzohydrazideHCID 86723854HCID 86723854, compound

Product 1

HCID 867238684-[4-[6-methyl-2,4-dioxo-3-propyl-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-4H-1,2,4-triazol-3-yl]benzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-cyanobenzohydrazide (46.0 mg) and dimethylformamide dimethylacetal (110 μl) in N,N-dimethy formamide (2.0 ml) was stirred at 50° C. for thirty minutes and then cooled to room temperature, and thereto were added 5-amino-6-methyl-3-propyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 193) (20.0 mg) and acetic acid (0.5 ml) and the resulting mixture was stirred at 130° C. for eight hours. To the reaction mixture was added water (10 ml) and the resulting mixture was extracted with ethyl acetate (10 ml×2). The organic layer was washed with water (10 ml×2) and 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: chloroform/methanol) to afford 4-[4-[6-methyl-2,4-dioxo-3-propyl-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-4H-1,2,4-triazol-3-yl]benzonitrile (7.8 mg).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate (10 ml×2)
  2. washThe organic layer was washed with water (10 ml×2) and saturated saline (20 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol)

Sources & evidence

ORD record
ord-e9f4b643600647d2a05067ef02f068f3
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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