Water → (+)-(6R)-9-(6,7-Dihydro-5H-[1]pyrindin-6-ylmethyl)-7,7-dimethyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

HRID 2375324Notes

Reaction equation

HRID 2375324 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][CH:12]=3)[N:10]=[C:5]2[NH:4][CH2:3]1.[H-].[Na+].[N:22]1[C:30]2[CH2:29][CH:28]([CH2:31]OS(C)(=O)=O)[CH2:27][C:26]=2[CH:25]=[CH:24][CH:23]=1.O>CN(C)C=O.C(Cl)Cl>[N:22]1[C:30]2[CH2:29][C@H:28]([CH2:31][N:4]3[C:5]4=[N:10][C:9]([C:11]5[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=5)=[CH:8][C:7](=[O:17])[N:6]4[CH2:18][C:2]([CH3:19])([CH3:1])[CH2:3]3)[CH2:27][C:26]=2[CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 87779704methanesulfonic acid 6,7-dihydro-5H-[1]pyrindin-6-ylmethyl esterHCID 1357386167,7-Dimethyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

Product 1

HCID 12073797(+)-(6R)-9-(6,7-Dihydro-5H-[1]pyrindin-6-ylmethyl)-7,7-dimethyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A suspension of 0.51 g (2 mmol) of 7,7-dimethyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 10 ml of anhydrous dimethylformamide was treated with 96 mg (2 mmol) of sodium hydride (50% suspension in mineral oil) and the resulting mixture was stirred for 40 min. 0.455 g (2 mmol) of methanesulfonic acid 6,7-dihydro-5H-[1]pyrindin-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 ethyl acetate/methanol/diethyl amine in the proportions 98/2/0.2 to give 0.3839 of pure product obtained in the form of free base. Mp: 182-184° C. [α]D20=+9.15° (c=0.5, CH2Cl2).

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 ethyl acetate/methanol/diethyl amine in the proportions 98/2/0.2
  8. customto give 0.3839 of pure product
  9. customobtained in the form of free base

Sources & evidence

ORD record
ord-2748a413907343d09ff7afdc60306c33
Source dataset
uspto-grants-2008_12
Patent number
US07465737B2

Reaction notes

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