Water → HCID 86723913, compound

HRID 576809Notes

Reaction equation

HRID 576809 reaction equation
[CH2:1]([N:3]1[C:8](=[O:9])[C:7]([C:10]2[N:14]([C:15]3[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=3)[N:13]=[CH:12][C:11]=2[C:23](O)([CH3:25])[CH3:24])=[C:6]([CH3:27])[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=2)[C:4]1=[O:38])[CH3:2].[N-:39]=[N+]=[N-].[Na+].FC(F)(F)C(O)=O.O>C(Cl)(Cl)Cl.C(OCC)(=O)C.C(O)(=O)C.[Zn]>[NH2:39][C:23]([C:11]1[CH:12]=[N:13][N:14]([C:15]2[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=2)[C:10]=1[C:7]1[C:8](=[O:9])[N:3]([CH2:1][CH3:2])[C:4](=[O:38])[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:36])([F:37])[F:35])[CH:29]=2)[C:6]=1[CH3:27])([CH3:24])[CH3:25]

Participants

9

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 33557Sodium AzideHCID 71514328HCID 71514328, compound

Product 1

HCID 86723913HCID 86723913, compoundYield 45.2%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent2×

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-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl)benzonitrile (prepared in Example 288) (114.7 mg) in chloroform (1.0 ml) was added at room temperature sodium azide (28.4 mg) and trifluoroacetic acid (200 μl) and the resulting mixture was stirred at room temperature for sixteen hours. The reaction mixture was diluted with ethyl acetate (30 ml) and the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to afford the residue. To a solution of the obtained residue in acetic acid (1.0 ml) were added at room temperature zinc dust (143.2 mg) and water (200 μl) and the resulting mixture was stirred at room temperature for eight hours. The reaction mixture was diluted with ethyl acetate (30 ml) and the solids were then filtered, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (10 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-(4-(2-aminopropane-2-yl)-5-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (51.8 mg). UPLC/MS 523 (M+H)/0.73 min. (measurement condition 9)

Workup

  1. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  2. concentrationconcentrated under reduced pressure
  3. customto afford the residue
  4. stirringthe resulting mixture was stirred at room temperature for eight hours
  5. filtrationthe solids were then filtered
  6. washthe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (10 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-4c889151983b462eb52e9a84897fc8fe
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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