Sodium hydride → 3-(2-Chloro-3,5-dimethoxy-phenyl)-1-ethyl-7-methylsulfanyl-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-one

HRID 1783551Notes

Reaction equation

HRID 1783551 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[CH:4][C:3]=1[NH:12][CH2:13][C:14]1[C:15]([NH:22][CH2:23][CH3:24])=[N:16][C:17]([S:20][CH3:21])=[N:18][CH:19]=1.[H-].[Na+].[C:27](N1C=CN=C1)(N1C=CN=C1)=[O:28]>CN(C=O)C>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[CH:4][C:3]=1[N:12]1[CH2:13][C:14]2[C:15](=[N:16][C:17]([S:20][CH3:21])=[N:18][CH:19]=2)[N:22]([CH2:23][CH3:24])[C:27]1=[O:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 68859404{5-[(2-Chloro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-ethyl-amine

Product 1

HCID 688581243-(2-Chloro-3,5-dimethoxy-phenyl)-1-ethyl-7-methylsulfanyl-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-oneYield 70.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a solution of 1.00 g (2.71 mmol) of {5-[(2-chloro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-ethyl-amine in 7 mL of dry DMF cooled to 5° C. was added 0.271 g (6.78 mmol) of sodium hydride as a 60% mineral oil suspension. The ice bath was removed, and the reaction was stirred for 1 hour. To the reaction was then added 1.32 g (8.13 mmol) of 1,1′-carbonyldiimidazole. After stirring a further 2 hours, the reaction was concentrated in vacuo. The residue was partitioned between dichloromethane and a saturated solution of ammonium chloride. The aqueous layer was washed twice with dichloromethane. The dichloromethane layers were combined, dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in dichloromethane, added silica gel, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with dichloromethane/ethyl acetate (9:0.5 v/v), to give 0.7507 g (70%) of the title compound: mp 189-191° C.

Workup

  1. customThe ice bath was removed
  2. stirringAfter stirring a further 2 hours
  3. concentrationthe reaction was concentrated in vacuo
  4. customThe residue was partitioned between dichloromethane
  5. washThe aqueous layer was washed twice with dichloromethane
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in dichloromethane
  9. additionadded silica gel
  10. concentrationconcentrated in vacuo
  11. customThe residue was chromatographed on silica gel
  12. washeluting with dichloromethane/ethyl acetate (9:0.5 v/v)

Sources & evidence

ORD record
ord-e7f13c0bddef486baca10e821bbee899
Source dataset
uspto-grants-2009_03
Patent number
US07501425B1

Reaction notes

Loading…