Water → HCID 178501546, compound

HRID 1280589Notes

Reaction equation

HRID 1280589 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:21][CH2:20]3)=[N:14][CH:15]=2)[NH:10][C:9]1=[O:33].[H-].[Na+].Br[CH2:37][C:38]([O:40][CH3:41])=[O:39].O>CN1CCCC1=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:18][C@H:19]3[CH2:20][CH2:21][C@H:22]([O:25][Si:26]([C:29]([CH3:30])([CH3:32])[CH3:31])([CH3:27])[CH3:28])[CH2:23][CH2:24]3)=[N:14][CH:15]=2)[N:10]([CH2:37][C:38]([O:40][CH3:41])=[O:39])[C:9]1=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 178455363HCID 178455363, compound

Product 1

HCID 178501546HCID 178501546, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-(Chlorophenyl)-7-(trans-4-tert-butyldimethylsilyloxycyclohexylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (972 mg, 2 mmol) (prepared as described in Example 81) was suspended in 1-methyl-2-pyrrolidinone (15 mL), and sodium hydride (88 mg, 2.2 mmol (60% oil dispersion)) was added. The reaction mixture was stirred at room temperature for 30 minutes, methyl bromoacetate (0.190 mL, 2 mmol) was added. The mixture was stirred for 6 hours. The reaction mixture was added to water and extracted with ethyl acetate, washed with water, dried over magnesium sulfate, and evaporated under reduced pressure. :The residue was purified by column chromatography on silica gel using 70:30 hexane/acetone as eluant. The fractions containing the product were combined and evaporated under reduced pressure to give 425 mg of 3-(2-chlorophenyl)-7-(trans-4-tert-butyldimethylsilyloxycyclohexylamino)-1-methoxycarbonylmethyl-3,4-dihydropyrimido-[4,5-d]pyrimidin-2(1H)-one as a white solid ((M+H)+560, m.p.165.7-167.4° C.

Workup

  1. stirringThe mixture was stirred for 6 hours
  2. extractionextracted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. custom:The residue was purified by column chromatography on silica gel using 70:30 hexane/acetone as eluant
  7. additionThe fractions containing the product
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9ca888445bc34dc8b641964abd0ff4a6
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Reaction notes

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