Benzyl Bromide → (8S)-9-benzyl-3-fluoro-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetra-hydro-4H-pyrimido[1,2-a]pyrimidin-4-one

HRID 80626Notes

Reaction equation

HRID 80626 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[F:15][C:16]1[C:21](=[O:22])[N:20]2[CH2:23][CH2:24][C@@H:25]([C:27]([F:30])([F:29])[F:28])[NH:26][C:19]2=[N:18][C:17]=1[N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>C(#N)C>[CH2:7]([N:26]1[C:19]2=[N:18][C:17]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:16]([F:15])[C:21](=[O:22])[N:20]2[CH2:23][CH2:24][C@H:25]1[C:27]([F:28])([F:30])[F:29])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 136350278(8S)-3-fluoro-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

Product 1

HCID 49854501(8S)-9-benzyl-3-fluoro-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetra-hydro-4H-pyrimido[1,2-a]pyrimidin-4-oneYield 46.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

4 g of caesium carbonate and 796 mg of benzyl bromide are added to a suspension of 1 g of (8S)-3-fluoro-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one in 11.8 ml of acetonitrile. After stirring overnight at a temperature in the region of 20° C., the suspension obtained is filtered and the resulting filtrate is concentrated to dryness under reduced pressure. The oily yellow residue is purified on a silica column (eluent: CH2Cl2/MeOH 98/02). The fractions of interest are combined and concentrated to dryness under reduced pressure. The residue is taken up with diethyl ether, spin-filter-dried and then dried under vacuum. 600 mg of (8S)-9-benzyl-3-fluoro-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetra-hydro-4 H-pyrimido[1,2-a]pyrimidin-4-one are thus obtained in the form of a white powder, the characteristics of which are the following:

Workup

  1. customthe suspension obtained
  2. filtrationis filtered
  3. concentrationthe resulting filtrate is concentrated to dryness under reduced pressure
  4. customThe oily yellow residue is purified on a silica column (eluent: CH2Cl2/MeOH 98/02)
  5. concentrationconcentrated to dryness under reduced pressure
  6. customspin-filter-dried
  7. customdried under vacuum

Sources & evidence

ORD record
ord-2b5429241ff1485f9b4668e951fc37e6
Source dataset
uspto-grants-2014_09
Patent number
US08846670B2

Reaction notes

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