Ammonium Chloride → HCID 58133708, compound

HRID 336925Notes

Reaction equation

HRID 336925 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H: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]([CH3:33])(=[O:32])=[O:31])[CH:4]=1)#[N:2].C[N:35](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]([NH2:35])=[O:17])=[C:13]([CH3:18])[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=3)[C:11](=[O:29])[NH:10]2)=[C:5]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58133811HCID 58133811, compound

Product 1

HCID 58133708HCID 58133708, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The reaction was carried out under argon. (4S)-4-[4-Cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (696 mg, 1.45 mmol; Example 5A) and HATU (2 eq., 1104 mg, 2.9 mmol) were initially charged in dry DMF (35 ml) at 0° C., and after brief stirring (20 min) ammonium chloride (5 eq., 388 mg, 7.26 mmol) and DIEA (7 eq., 1314 mg, 10.16 mmol) were added. The mixture was stirred at RT for 4 h (monitored by HPLC). The mixture was then concentrated, and the residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave a colorless amorphous solid (612 mg, 88% of theory).

Workup

  1. additionwere added
  2. concentrationThe mixture was then concentrated
  3. customthe residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  4. customThis gave a colorless amorphous solid (612 mg, 88% of theory)

Sources & evidence

ORD record
ord-3c47cc8ea5bf4dbaa0705ae568485cf2
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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