Water → 9-(6,7-Dihydro-5H-cyclopentapyrazin-6-ylmethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-alpha]pyrimidin-4-one

HRID 2375338Notes

Reaction equation

HRID 2375338 reaction equation
[CH3:1][C:2]1([CH3:19])[CH2:18][N:6]2[C:7](=[O:17])[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][N:12]=3)[N:10]=[C:5]2[NH:4][CH2:3]1.[H-].[Na+].[N:22]1[C:27]2[CH2:28][CH:29]([CH2:31]OS(C)(=O)=O)[CH2:30][C:26]=2[N:25]=[CH:24][CH:23]=1.O>CN(C)C=O>[N:22]1[C:27]2[CH2:28][CH:29]([CH2:31][N:4]3[C:5]4=[N:10][C:9]([C:11]5[CH:16]=[CH:15][N:14]=[CH:13][N:12]=5)=[CH:8][C:7](=[O:17])[N:6]4[CH2:18][C:2]([CH3:19])([CH3:1])[CH2:3]3)[CH2:30][C:26]=2[N:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 86615340methanesulfonic acid 6,7-dihydro-5H-cyclopentapyrazin-6-ylmethyl esterHCID 1360828947,7-Dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

Product 1

HCID 179562929-(6,7-Dihydro-5H-cyclopentapyrazin-6-ylmethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-alpha]pyrimidin-4-oneYield 10.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A suspension of 0.5 g (1.94 mmol) of 7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 10 ml of anhydrous dimethylformamide was treated with 155 mg (3.89 mmol) of sodium hydride (50% suspension in mineral oil) and the resulting mixture was stirred for 40 min at 50° C. 0.888 g (3.89 mmol) of methanesulfonic acid 6,7-dihydro-5H-cyclopentapyrazin-6-ylmethyl ester in 2 ml of anhydrous dimethylformamide was added and the reaction mixture stirred at room temperature for 18 h. The solution was treated with water and extracted with ethyl acetate. The organic phase was dried and evaporated to give crude product, which was purified by silica gel chromatography, eluting with dichloromethane/methanol in the proportions 100/1 to 95/5 to give 80 mg of pure product obtained in the form of free base which was transformed into the hydrochloride salt. Mp: 193-195° C.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 18 h
  2. extractionextracted with ethyl acetate
  3. customThe organic phase was dried
  4. customevaporated
  5. customto give crude product, which
  6. customwas purified by silica gel chromatography
  7. washeluting with dichloromethane/methanol in the proportions 100/1 to 95/5

Sources & evidence

ORD record
ord-37b71de9c4c0471294caf0b1c03d2f1f
Source dataset
uspto-grants-2008_12
Patent number
US07465737B2

Reaction notes

Loading…