4-(Dimethylamino)butan-1-ol → 4-(dimethylamino)butyl 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylate

HRID 576795

Reaction equation

HRID 576795 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[C:15](=[O:33])[N:16]([CH3:32])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[C:12]([C:34]([OH:36])=[O:35])[CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].[CH3:37][N:38]([CH3:44])[CH2:39][CH2:40][CH2:41][CH2:42]O.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>C(#N)C.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([C:14]3[C:15](=[O:33])[N:16]([CH3:32])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=4)[C:19]=3[CH3:20])=[C:12]([C:34]([O:36][CH2:42][CH2:41][CH2:40][CH2:39][N:38]([CH3:44])[CH3:37])=[O:35])[CH:11]=[N:10]2)=[CH:7][CH:8]=1)#[N:2]

Participants

8

Reactant 5

HCID 833504-(Dimethylamino)butan-1-olHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712514111-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 715147964-(dimethylamino)butyl 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylic acid (prepared in Example 132) (153 mg) in acetonitrile (5 ml) was added 4-dimethylaminobutanol (0.21 ml), 1-hydroxy-7-azabenzotriazole (126 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (177 mg) and the resulting mixture was stirred at room temperature for sixteen hours. To the reaction solution were added saturated aqueous sodium hydrogen carbonate solution (10 ml) and ethyl acetate (20 ml×2) such that the intended products were extracted into an organic layer. The organic layer was washed with saturated saline (20 ml), dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol) to afford 4-(dimethylamino)butyl 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylate (137 mg). UPLC/MS 595 (M+H)/0.73 min (measurement condition 9)

Workup

  1. extractionwere extracted into an organic layer
  2. washThe organic layer was washed with saturated saline (20 ml)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol)

Sources & evidence

ORD record
ord-3d33d6ee08624d2b82867cbab91ecfaf
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Linked notes

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