Triethylamine → HCID 58133703, compound

HRID 336966Notes

Reaction equation

HRID 336966 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])[NH:10]2)=[C:5]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:4]=1)#[N:2].Br[CH2:35][CH2:36][OH:37].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][CH2:35][CH2:36][OH:37])=[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])[NH:10]2)=[C:5]([S:30]([CH3:33])(=[O:31])=[O:32])[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 58133811HCID 58133811, compound

Product 1

HCID 58133703HCID 58133703, compoundYield 94.2%

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]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (170 mg, 355 μmol; Example 5A) was initially charged in dry DMF (4 ml), 2-bromoethanol (177 mg, 1.42 mmol; 4 eq.) and triethylamine (72 mg, 709 μmol; 2 eq.) were added and the mixture was stirred at 70° C. for 10 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 purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave the title compound as a solid (175 mg, 94% 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. customThe crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)

Sources & evidence

ORD record
ord-5ca9e1d60eee416d9d4e647369e4a262
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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