3-Bromo-1,1,1-trifluoro-2-propanone → AZD7118 Bromo Trifluoromethyl

HRID 2243062Notes

Reaction equation

HRID 2243062 reaction equation
Br[CH2:2][C:3](=[O:8])[C:4]([F:7])([F:6])[F:5].[Br:9][C:10]1[C:11]([C:22](=[S:24])[NH2:23])=[CH:12][C:13]([NH:16][C:17]([NH:19][CH2:20][CH3:21])=[O:18])=[N:14][CH:15]=1>C(#N)C>[Br:9][C:10]1[C:11]([C:22]2[S:24][CH2:2][C:3]([OH:8])([C:4]([F:7])([F:6])[F:5])[N:23]=2)=[CH:12][C:13]([NH:16][C:17]([NH:19][CH2:20][CH3:21])=[O:18])=[N:14][CH:15]=1

Participants

4

Reactant 2

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 59208439AZD7118 Bromo Thioamide2×

Product 1

HCID 59208483AZD7118 Bromo TrifluoromethylYield 31.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

3-Bromo-1,1,1-trifluoropropan-2-one (2.260 mL, 21.77 mmol) was added to a mixture of 5-bromo-2-(3-ethylureido)pyridine-4-carbothioamide (Intermediate 42, 1.1 g, 3.63 mmol) in acetonitrile (25 mL), and the reaction mixture was heated at 80° C. for 4 h. After a clear solution resulted within an hour, and the solution was concentrated under reduced pressure and the resulting residue was partitioned between water and ethyl acetate. The organic layer was washed with water and brine, dried over magnesium sulfate, then concentrated under reduced pressure to give light yellow solid, which was purified by normal phase column chromatography (silica, 2% MeOH in dichloromethane to 5% MeOH in dichloromethane) to give the title compound as a white solid (470 mg). MS (ESP): 414 (M+1) for C12H12BrF3N4O2S; NMR: 1.06 (t, 3H); 3.12-3.18 (m, 2H); 3.60 (dd, 1H); 3.90 (dd, 1H); 7.13 (brs, 1H); 7.98 (s, 1H); 8.47 (s, 1H); 9.41 (s, 1H).

Workup

  1. customAfter a clear solution resulted within an hour
  2. concentrationthe solution was concentrated under reduced pressure
  3. customthe resulting residue was partitioned between water and ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give light yellow solid, which
  8. customwas purified by normal phase column chromatography (silica, 2% MeOH in dichloromethane to 5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-ffe7363c9174454997a10b9cbfc84fdf
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

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