Acetic Acid → HCID 71513859, compound

HRID 576767Notes

Reaction equation

HRID 576767 reaction equation
[NH2:1][C:2]1[C:3](=[O:23])[N:4]([CH:20]([CH3:22])[CH3:21])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].[CH3:24]OC(OC)N(C)C.C(O)(=O)C.[C:36]([C:38]1[CH:47]=[CH:46][C:41]([C:42]([NH:44][NH2:45])=O)=[CH:40][CH:39]=1)#[N:37]>CN(C)C=O.O>[CH:20]([N:4]1[C:3](=[O:23])[C:2]([N:1]2[CH:24]=[N:45][N:44]=[C:42]2[C:41]2[CH:46]=[CH:47][C:38]([C:36]#[N:37])=[CH:39][CH:40]=2)=[C:7]([CH3:8])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:17])([F:16])[F:18])[CH:10]=2)[C:5]1=[O:19])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 78373Dimethylformamide dimethyl acetalHCID 4567324-CyanobenzohydrazideHCID 86723869HCID 86723869, compound

Product 1

HCID 71513859HCID 71513859, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-isopropyl-6-methyl-5-nitro-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 195) (1.68 g) in ethyl acetate/methanol (20.0 ml/20.0 ml) was added palladium hydroxide (500.0 mg) and the resulting mixture was performed catalytic hydrogenation at room temperature for four and a half hours. The reaction mixture was degassed and then filtered through Celite (trade mark) and then concentrated under reduced pressure to afford the residue (897.0 mg) containing 5-amino-3-isopropyl-6-methyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione. A solution of the resulting residue (150.0 mg), dimethylformamide dimethylacetal (340 μl) and acetic acid (7 μl) in N,N-dimethy formamide (4.0 ml) was stirred at 110° C. for forty-five minutes and then cooled to room temperature, and thereto were added 4-cyanobenzohydrazide (221.4 mg) and acetic acid (690 μl) and the resulting mixture was stirred at 130° C. for two hours. To the reaction mixture was added water (30 ml) and the resulting mixture was extracted with ethyl acetate (30 ml×2). The organic layer was washed with water (30 ml×2) 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) and aminosilica gel column chromatography (eluent: ethyl acetate/methanol) to afford 4-(4-(3-isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)benzonitrile (64.1 mg).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate (30 ml×2)
  2. washThe organic layer was washed with water (30 ml×2) and saturated saline (30 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-2329a1ae4404460f8923de88d5c85f77
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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