Cesium carbonate → (8S)-2-chloro-9-[2-(4-methylthiazol-5-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one

HRID 633715Notes

Reaction equation

HRID 633715 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[NH:12][C@H:11]([C:13]([F:16])([F:15])[F:14])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br.Br[CH2:25][C:26]([C:28]1[S:32][CH:31]=[N:30][C:29]=1[CH3:33])=[O:27]>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]2[N:12]([CH2:25][C:26]([C:28]3[S:32][CH:31]=[N:30][C:29]=3[CH3:33])=[O:27])[C@H:11]([C:13]([F:14])([F:15])[F:16])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1317354732-Bromo-1-(4-methylthiazol-5-yl)ethanone hydrobromideHCID 136238740(S)-8-chloro-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one

Product 1

HCID 118194378(8S)-2-chloro-9-[2-(4-methylthiazol-5-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-oneYield 81.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 150 mg (0.591 mmol) of (8S)-2-chloro-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 578.13 mg (1.77 mmol) of cesium carbonate in 10 mL of acetonitrile is stirred for 15 minutes at room temperature. 213.64 mg (0.709 mmol) of 2-bromo-1-(4-methylthiazol-5-yl)ethanone hydrobromide are then added. After stirring overnight at room temperature, the reaction mixture is evaporated and the residue is taken up in water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and evaporated to dryness to give 190 mg of (8S)-2-chloro-9-[2-(4-methylthiazol-5-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one, corresponding to the following characteristics:

Workup

  1. stirringAfter stirring overnight at room temperature
  2. customthe reaction mixture is evaporated
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-ab239ab80b834187b482f8644dc0e33f
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

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