Sodium hydride → (S)-7-chloro-2-methyl-1-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one

HRID 633750Notes

Reaction equation

HRID 633750 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[NH:11][C@:10]([CH3:16])([C:12]([F:15])([F:14])[F:13])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.[H-].[Na+].Br.Br[CH2:21][C:22]([C:24]1[CH:25]=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=1)=[O:23]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]2[N:11]([CH2:21][C:22]([C:24]3[CH:25]=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=3)=[O:23])[C@:10]([CH3:16])([C:12]([F:13])([F:14])[F:15])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 454805112-Bromo-1-(6-methylpyridin-3-yl)ethanone hydrobromideHCID 136069597(2S)-7-chloro-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

Product 1

HCID 118194434(S)-7-chloro-2-methyl-1-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

500 mg (1.97 mmol) of (S)-7-chloro-2-methyl-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one are added to a suspension of 141.94 mg (5.91 mmol) of sodium hydride in 20 mL of DMF. The reaction mixture is placed under magnetic stirring at room temperature for 15 minutes. A solution of 872.32 mg (2.96 mmol) of 2-bromo-1-(6-methylpyrid-3-yl)ethanone hydrobromide in 10 mL of DMF is added dropwise to the reaction medium at 0° C. The reaction is stirred at room temperature overnight. The reaction medium is evaporated to dryness. The crude product is taken up in water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and evaporated to dryness. After purification by chromatography on silica gel (eluent A/B: heptane/EtOAc, gradient A/B: t 0 min 30% B, t 35 min 60% B, t 40 min 60% B), 150 mg of (S)-7-chloro-2-methyl-1-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one were obtained, corresponding to the following characteristics:

Workup

  1. stirringThe reaction is stirred at room temperature overnight
  2. customThe reaction medium is evaporated to dryness
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. customevaporated to dryness
  6. customAfter purification by chromatography on silica gel (eluent A/B: heptane/EtOAc, gradient A/B: t 0 min 30% B, t 35 min 60% B, t 40 min 60% B), 150 mg of (S)-7-chloro-2-methyl-1-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-2-trifluoromethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
  7. customwere obtained, corresponding to the following characteristics

Sources & evidence

ORD record
ord-d63dddd997ea41a5a4ab0e5c9e3f1d7a
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

Loading…