[(2,4-Dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine → HCID 178491934, compound

HRID 1243186Notes

Reaction equation

HRID 1243186 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][N:3]=1.C([Li])CCC.[C:24]([Si:28]([O:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([N:38]=[C:39]=[O:40])[CH2:34][CH2:33]1)([CH3:30])[CH3:29])([CH3:27])([CH3:26])[CH3:25]>O1CCCC1.C(OCC)(=O)C>[C:24]([Si:28]([CH3:30])([CH3:29])[O:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([N:38]2[C:6]3=[N:7][C:2]([Cl:1])=[N:3][CH:4]=[C:5]3[CH2:9][N:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:39]2=[O:40])[CH2:34][CH2:33]1)([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 21939303[(2,4-Dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amineHCID 178418339ButyllithiumHCID 178455365HCID 178455365, compound

Product 1

HCID 178491934HCID 178491934, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of [(2,4-dichloropyrimidin-5-yl)methyl](4-methoxy-phenyl)amine (1.0 g, 3.52 mmol) (from Example 1d supra) in tetrahydrofuran (50 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 1.7 mL, 4.22 mmol) (Aldrich). After stirring at −78° C. for 20 minutes, tert-butyl-(trans-4-isocyanato-cyclohexyloxy)-dimethyl-silane (1.1 g, 4.22 mmol) (from Example 17b supra) was added. The mixture was stirred at −70° C. for 1 hour and then at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with ethyl acetate-hexanes (3:7 then 2:3) to give 1-[trans-4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-7-chloro-3-(4-methoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.61 g, 34%).

Workup

  1. stirringThe mixture was stirred at −70° C. for 1 hour
  2. waitat room temperature for 3 hours
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography
  8. washeluting with ethyl acetate-hexanes (3:7

Sources & evidence

ORD record
ord-c9def535b167420790bb61f77ab242e4
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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