(R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea → (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 1243224Notes

Reaction equation

HRID 1243224 reaction equation
[C:1]([Si:5]([CH3:32])([CH3:31])[O:6][CH2:7][C@H:8]([NH:10][C:11](=[O:30])[N:12]([CH2:21][C:22]1[C:23](Cl)=[N:24][C:25]([Cl:28])=[N:26][CH:27]=1)[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH3:20])=[CH:15][CH:14]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+]>O1CCCC1>[C:1]([Si:5]([CH3:31])([CH3:32])[O:6][CH2:7][C@H:8]([N:10]1[C:23]2=[N:24][C:25]([Cl:28])=[N:26][CH:27]=[C:22]2[CH2:21][N:12]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH3:20])=[CH:15][CH:14]=2)[C:11]1=[O:30])[CH3:9])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 11488861(R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-ureaHCID 23665647Potassium tert-butoxide

Product 1

HCID 11271157(R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea (380 mg, 0.76 mmol) (from Example 38d supra) in tetrahydrofuran (10 mL) was treated at room temperature with potassium tert-butoxide (160 mg, 1.14 mmol) (Aldrich). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue (395 mg, yellow oil) was purified by flash chromatography to give (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a colorless oil. (Yield 102 mg, 30%).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue (395 mg, yellow oil) was purified by flash chromatography

Sources & evidence

ORD record
ord-9efb35800a284290b1f04559d72d9eca
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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