Sodium Hydroxide → (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

HRID 80625Notes

Reaction equation

HRID 80625 reaction equation
[OH-].[Na+].Br[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=1.[N:13]1([C:19]2[N:20]=[C:21]3[NH:29][C@H:28]([C:30]([F:33])([F:32])[F:31])[CH2:27][CH2:26][N:22]3[C:23](=[O:25])[CH:24]=2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:12][C:8]1[CH:7]=[C:6]([CH2:5][CH2:4][N:29]2[C:21]3=[N:20][C:19]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[CH:24][C:23](=[O:25])[N:22]3[CH2:26][CH2:27][C@H:28]2[C:30]([F:31])([F:32])[F:33])[CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 5731291-(2-Bromoethyl)-3-fluorobenzeneHCID 136238743(S)-8-(Morpholin-4-yl)-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one

Product 1

HCID 49854500(8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

296 mg of sodium hydroxide in 2.5 ml of water, 33 mg of tetrabutylammonium hydrogen sulphate and 200 mg of 1-(2-bromoethyl)-3-fluorobenzene are added to a solution of 150 mg of (8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one in 2.5 ml of toluene. After one hour under microwave irradiation (power 100 watts on a CEM discover apparatus) at 60° C. and then one hour again at 60° C. and twice six hours at 70° C., the reaction mixture is diluted with ethyl acetate. The resulting mixture is washed with water. The organic phase is separated and then concentrated to dryness under reduced pressure. After purification of the resulting residue by preparative HPLC/MS (method D), 43 mg of (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one are obtained, the characteristics of which are the following:

Workup

  1. customAfter one hour under microwave irradiation (power 100 watts on a CEM
  2. customat 60° C.
  3. washThe resulting mixture is washed with water
  4. customThe organic phase is separated
  5. concentrationconcentrated to dryness under reduced pressure
  6. customAfter purification of the resulting residue by preparative HPLC/MS (method D), 43 mg of (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one
  7. customare obtained

Sources & evidence

ORD record
ord-e697ecd0b908460499ea9bc15fa69867
Source dataset
uspto-grants-2014_09
Patent number
US08846670B2

Reaction notes

Loading…