4-Methylmorpholine → 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-(hydroxymethyl)-1H-pyrazol-1-yl)benzonitrile

HRID 576792Notes

Reaction equation

HRID 576792 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](O)=[O:35])[CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+].[Cl-].[NH4+]>O1CCCC1.O>[CH3:32][N:16]1[C:15](=[O:33])[C:14]([C:13]2[N:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[N:10]=[CH:11][C:12]=2[CH2:34][OH:35])=[C:19]([CH3:20])[N:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=2)[C:17]1=[O:31]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydride2×HCID 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 867239034-(5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-(hydroxymethyl)-1H-pyrazol-1-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(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 (prepared in Example 132) (100 mg) and N-methylmorpholine (66 μL) in tetrahydrofuran (2 ml) was added at 0° C. isobutyl chloroformate (79 μl). After thirty minutes, to the reaction mixture was added sodium borohydride (26.4 mg) and the resulting mixture was stirred for three and a half hours. Thereto was added sodium borohydride (55.6 mg) and the mixture was stirred for another thirty minutes and thereto were added water and saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over sodium sulfate, and then concentrated on evaporator instrument. The residue was purified by silica gel column chromatography to afford the intended 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-(hydroxymethyl)-1H-pyrazol-1-yl)benzonitrile.

Workup

  1. waitAfter thirty minutes
  2. stirringthe mixture was stirred for another thirty minutes
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated on evaporator instrument
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6c50729be8254027b37fd33f24e41327
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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