Cesium carbonate → (8S)-9-(3,5-difluorobenzyl)-2-(morpholin-4-yl)-8-(trifluoro-methyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

HRID 80619Notes

Reaction equation

HRID 80619 reaction equation
[N:1]1([C:7]2[N:8]=[C:9]3[NH:17][C@H:16]([C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14][N:10]3[C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:29][C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[CH:31]=1>CN(C)C=O>[F:36][C:34]1[CH:35]=[C:30]([CH:31]=[C:32]([F:37])[CH:33]=1)[CH2:29][N:17]1[C:9]2=[N:8][C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[CH:12][C:11](=[O:13])[N:10]2[CH2:14][CH2:15][C@H:16]1[C:18]([F:20])([F:21])[F:19]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5188963,5-Difluorobenzyl bromideHCID 136238743(S)-8-(Morpholin-4-yl)-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one

Product 1

HCID 49854298(8S)-9-(3,5-difluorobenzyl)-2-(morpholin-4-yl)-8-(trifluoro-methyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product is prepared according to the procedure described in Example 22, using 100 mg of (8S)-2-morpholin-4-yl-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one (Example 1e), 214 mg of caesium carbonate and 75 mg of 1-(bromomethyl)-3,5-difluorobenzene in 2 ml of dimethylformamide. After purification by preparative HPLC/MS (Method C), 85 mg of (8S)-9-(3,5-difluorobenzyl)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one are obtained in the form of an oil, the characteristics of which are the following:

Workup

  1. customThe product is prepared
  2. customAfter purification by preparative HPLC/MS (Method C), 85 mg of (8S)-9-(3,5-difluorobenzyl)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
  3. customare obtained in the form of an oil

Sources & evidence

ORD record
ord-30376f3ba76943e08dd4d09acad6eb31
Source dataset
uspto-grants-2014_09
Patent number
US08846670B2

Reaction notes

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