Triethylamine → HCID 58133837, compound

HRID 2064408Notes

Reaction equation

HRID 2064408 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]([OH:17])=[O:16])=[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])[N:10]2[CH3:30])=[C:5]([S:31]([CH3:34])(=[O:33])=[O:32])[CH:4]=1)#[N:2].Br[CH2:36][CH2:37][OH:38].C(N(CC)CC)C>CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]([O:17][CH2:36][CH2:37][OH:38])=[O:16])=[C:13]([CH3:18])[N:12]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=3)[C:11](=[O:29])[N:10]2[CH3:30])=[C:5]([S:31]([CH3:34])(=[O:32])=[O:33])[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 58133803HCID 58133803, compound

Product 1

HCID 58133837HCID 58133837, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

The reaction was carried out under argon. (4S)-4-[4-Cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (74 mg, 150 μmol) was initially charged in dry DMF (2 ml), 2-bromoethanol (75 mg, 600 μmol; 4 eq.) and triethylamine (31 mg, 300 μmol; 2 eq.) were added and the mixture was stirred at 70° C. for 8 h. The reaction mixture was then concentrated under reduced pressure, and the residue was taken up in ethyl acetate (50 ml). The organic phase was washed with saturated sodium bicarbonate solution (2×20 ml) and saturated sodium chloride solution (20 ml), dried over solid sodium sulfate, filtered and concentrated under reduced pressure. The crude product was subjected to flash chromatography on silica gel (mobile phase: cyclohexane→cyclohexane/ethyl acetate 1:3). The product-containing fractions were combined and concentrated, the residue was taken up in a little acetonitrile, water was added and the mixture was lyophilized. The title compound was obtained as a colorless solid (63 mg, 78% of theory).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. washThe organic phase was washed with saturated sodium bicarbonate solution (2×20 ml) and saturated sodium chloride solution (20 ml)
  3. dry with materialdried over solid sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. concentrationconcentrated
  7. additionwas added

Sources & evidence

ORD record
ord-dfb56e0df0944734b215abbbbeb6f47d
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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