Triethylamine → n-(6-Amino-2,4-dioxo-3-propyl(1,3-dihydropyrimidin-5-yl))(1-{[3-(trifluoromethyl)phenyl]methyl}pyrazol-4-yl)carboxamide

HRID 1929733Notes

Reaction equation

HRID 1929733 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[CH:14]=[C:13]([C:15]([OH:17])=O)[CH:12]=[N:11]2)[CH:6]=[CH:7][CH:8]=1.[NH2:20][C:21]1[C:22](=[O:32])[N:23]([CH2:29][CH2:30][CH3:31])[C:24](=O)[NH:25][C:26]=1[NH2:27].C(N(CC)CC)C.S(Cl)(Cl)=[O:41]>C(#N)C>[NH2:27][C:26]1[NH:25][CH2:24][N:23]([CH2:29][C:30](=[O:41])[CH3:31])[C:22](=[O:32])[C:21]=1[NH:20][C:15]([C:13]1[CH:12]=[N:11][N:10]([CH2:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:19])[F:18])[CH:4]=2)[CH:14]=1)=[O:17]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 109542025,6-Diamino-3-propylpyrimidine-2,4(1H,3H)-dioneHCID 114927411-(3-(Trifluoromethyl)benzyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 131726003n-(6-Amino-2,4-dioxo-3-propyl(1,3-dihydropyrimidin-5-yl))(1-{[3-(trifluoromethyl)phenyl]methyl}pyrazol-4-yl)carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-{[3-(trifluoromethyl)phenyl]methyl}pyrazole-4-carboxylic acid (1 g, 3.7 mmol) in thionyl chloride (1 ml) was heated at 70° C. for 4 hours. Excess thionyl chloride was distilled off, and the residue treated with methylene chloride/hexanes. The solvent was removed under reduced pressure, and the residue dissolved in acetonitrile. This solution was added to a suspension of 5,6-diamino-3-propyl-1,3-dihydropyrimidine-2,4-dione (2.3 g, 126 mmol) and triethylamine (1 ml) in acetonitrile (20 ml) at 0° C., and stirred for 16 hours. The reaction mixture was quenched with water (5 ml), acidified with hydrochloric acid, stirred for 30 minutes, and the precipitate filtered off. The product was washed with ether, to provide N-(6-amino-2,4-dioxo-3-propyl(1,3-dihydropyrimidin-5-yl))(1-{[3-(trifluoromethyl)phenyl]methyl}pyrazol-4-yl)carboxamide, a compound of formula (13).

Workup

  1. distillationExcess thionyl chloride was distilled off
  2. additionthe residue treated with methylene chloride/hexanes
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue dissolved in acetonitrile
  5. customThe reaction mixture was quenched with water (5 ml)
  6. stirringstirred for 30 minutes
  7. filtrationthe precipitate filtered off
  8. washThe product was washed with ether

Sources & evidence

ORD record
ord-95a32ad5973e44dcb25b76427a2c3108
Source dataset
uspto-grants-2012_05
Patent number
US08188099B2

Reaction notes

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