Ammonia → (rac)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxamide

HRID 707598Notes

Reaction equation

HRID 707598 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([OH:17])=O)=[C:13]([CH3:18])[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:11](=[O:29])[NH:10]2)=[C:5]([S:30]([CH2:33][CH3:34])(=[O:32])=[O:31])[CH:4]=1)#[N:2].C[N:36](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N.O1CCOCC1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([NH2:36])=[O:17])=[C:13]([CH3:18])[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:28])[F:27])[CH:20]=3)[C:11](=[O:29])[NH:10]2)=[C:5]([S:30]([CH2:33][CH3:34])(=[O:31])=[O:32])[CH:4]=1)#[N:2]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58133746(rac)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Product 1

HCID 58133836(rac)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The reaction was carried out under argon. (rac)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (1100 mg, 2.29 mmol) and HATU (2 eq., 1695 mg, 4.5 mmol) were initially charged in dry DMF (28 ml) at 0° C., and a 0.5 M solution of ammonia in dioxane (6 eq., 23.6 ml, 13.4 mmol) and DIEA (2 eq., 576 mg, 4.5 mmol) were added after brief stirring (20 min). The mixture was stirred at RT for 3 h (HPLC control). The reaction mixture was then diluted with ethyl acetate (200 ml). The organic phase was washed successively with saturated sodium bicarbonate solution (50 ml), 10% strength citric acid (3×50 ml) and saturated sodium chloride solution (50 ml), dried over solid sodium sulfate, filtered and concentrated. The residue was subjected to flash chromatography on silica gel (mobile phase: dichloromethane→dichloromethane/methanol 50:3). This gave a colorless solid (1050 mg, 96% of theory).

Workup

  1. stirringThe mixture was stirred at RT for 3 h (HPLC control)
  2. washThe organic phase was washed successively with saturated sodium bicarbonate solution (50 ml), 10% strength citric acid (3×50 ml) and saturated sodium chloride solution (50 ml)
  3. dry with materialdried over solid sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis gave a colorless solid (1050 mg, 96% of theory)

Sources & evidence

ORD record
ord-8dcb7ce4c3ab436393f978165ee45be7
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

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