Sodium hydride → 6,7,8,9-Tetrahydro-7,7-dimethyl-9-[2-(1-methylethoxy)ethyl]-2-(4-morpholinyl)-4H-pyrimido[1,2-a]pyrimidin-4-one

HRID 2408360Notes

Reaction equation

HRID 2408360 reaction equation
[CH3:1][C:2]1([CH3:19])[CH2:18][N:6]2[C:7](=[O:17])[CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:10]=[C:5]2[NH:4][CH2:3]1.[H-].[Na+].CS(O[CH2:27][CH2:28][O:29][CH:30]([CH3:32])[CH3:31])(=O)=O>CN(C=O)C>[CH:30]([O:29][CH2:28][CH2:27][N:4]1[C:5]2=[N:10][C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][C:7](=[O:17])[N:6]2[CH2:18][C:2]([CH3:19])([CH3:1])[CH2:3]1)([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 184650452-Isopropoxyethyl MethanesulfonateHCID 136344291HCID 136344291, compound

Product 1

HCID 574071376,7,8,9-Tetrahydro-7,7-dimethyl-9-[2-(1-methylethoxy)ethyl]-2-(4-morpholinyl)-4H-pyrimido[1,2-a]pyrimidin-4-oneYield 35.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.17 g of 7,7-dimethyl-2-(morpholin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]-pyrimidin-4-one are solubilized in anhydrous DMF. 0.03 g of 60% NaH are added and stirring is performed for 30 mins. 0.24 g of 2-isopropoxyethyl methanesulfonate are added and the mixture is heated with reflux for 3 h. After returning to RT, the mixture is poured in a water/ice/AcOEt mixture. The organic phase is decanted, washed with a solution saturated with NaCl and then dried with magnesium sulfate. The solvents are evaporated. The crude is purified by flash chromatography on silica gel (CH2Cl2/MeOH, 95/5). 0.08 g (yield=35%) of 9-(2-isopropoxyethyl)-7,7-dimethyl-2-(morpholin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one are obtained as a white powder including the following characteristics:

Workup

  1. temperaturethe mixture is heated
  2. temperaturewith reflux for 3 h
  3. customAfter returning to RT
  4. customThe organic phase is decanted
  5. washwashed with a solution saturated with NaCl
  6. dry with materialdried with magnesium sulfate
  7. customThe solvents are evaporated
  8. customThe crude is purified by flash chromatography on silica gel (CH2Cl2/MeOH, 95/5)

Sources & evidence

ORD record
ord-2ce6105142a945afa2941d06f1c101b5
Source dataset
uspto-grants-2014_08
Patent number
US08815853B2

Reaction notes

Loading…