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

HRID 2064399Notes

Reaction equation

HRID 2064399 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]([CH:33]([CH3:35])[CH3:34])(=[O:32])=[O:31])[CH:4]=1)#[N:2].C[N:37](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:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([NH2:37])=[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]([CH:33]([CH3:34])[CH3:35])(=[O:32])=[O:31])[CH:4]=1)#[N:2]

Participants

7

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 58133736(rac)-4-{4-Cyano-2-[(1-methylethyl)sulfonyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Product 1

HCID 58133733(rac)-4-{4-Cyano-2-[(1-methylethyl)sulfonyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The reaction was carried out under argon. (rac)-4-{4-Cyano-2-[(1-methylethyl)sulfonyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (1000 mg, 1.97 mmol) and HATU (3 eq., 2248 mg, 5.9 mmol) were initially charged in dry DMF (25 ml) at 0° C., and a 0.5 M solution of ammonia in dioxane (3 eq., 11.8 ml, 5.9 mmol) and DIEA (3 eq., 764 mg, 5.9 mmol) were added after brief stirring (20 min). The mixture was stirred at RT for 6 h (HPLC control) and then concentrated under reduced pressure. The crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). The title compound was obtained as a solid (750 mg, 75% of theory).

Workup

  1. stirringThe mixture was stirred at RT for 6 h (HPLC control)
  2. concentrationconcentrated under reduced pressure
  3. customThe crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20)

Sources & evidence

ORD record
ord-a02c7a62aee04ecfbfd5118f6f14e03b
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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