(4R)-4-(4-Cyano-2-nitrophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile → (4R)-4-(2-Amino-4-cyanophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

HRID 336920

Reaction equation

HRID 336920 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[N:10]2[CH3:29])=[C:5]([N+:30]([O-])=O)[CH:4]=1)#[N:2]>CO.[Pd]>[NH2:30][C:5]1[CH:4]=[C:3]([C:1]#[N:2])[CH:8]=[CH:7][C:6]=1[C@@H:9]1[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[C:11](=[O:28])[N:10]1[CH3:29]

Participants

4

Reactant 1

HCID 66601573(4R)-4-(4-Cyano-2-nitrophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Product 1

HCID 66601757(4R)-4-(2-Amino-4-cyanophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Under argon, (4R)-4-(4-cyano-2-nitrophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (6.0 g, 11.3 mmol) was dissolved in methanol (420 ml). 10% palladium on activated carbon (5.5 g) was then added, and the mixture was hydrogenated at RT and atmospheric pressure for 5.5 h (strictly monitored by HPLC). The reaction mixture was then filtered off over kieselguhr, and the filter residue was washed with methanol (1000 ml). The filtrate was concentrated and the crude product was subjected to flash chromatography on silica gel (mobile phase: ethyl acetate/cyclohexane 2:1). The title compound was obtained as a solid (2.28 g, 40% of theory).

Workup

  1. customwas hydrogenated at RT
  2. filtrationThe reaction mixture was then filtered off over kieselguhr
  3. washthe filter residue was washed with methanol (1000 ml)
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-540703315bfb498699d96dcf50554942
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Linked notes

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