(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine → HCID 178491935, compound

HRID 1243183Notes

Reaction equation

HRID 1243183 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][C:12]=2[F:19])=[CH:4][N:3]=1.C([Li])CCC.[C:25]([Si:29]([O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]=[C:40]=[O:41])[CH2:35][CH2:34]1)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.C(OCC)(=O)C>[C:25]([Si:29]([CH3:31])([CH3:30])[O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]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][C:12]=3[F:19])[C:40]2=[O:41])[CH2:35][CH2:34]1)([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 21939275(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amineHCID 178418339ButyllithiumHCID 178455365HCID 178455365, compound

Product 1

HCID 178491935HCID 178491935, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (2,4-dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine (1.1 g, 3.64 mmol) (from Example 17a supra) in tetrahydrofuran (50 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 1.75 mL, 4.37 mmol) (Aldrich). After stirring at −78° C. for 40 minutes, tert-butyl-(trans-4-isocyanato-cyclohexyloxy)-dimethyl-silane (1.12 g, 4.37 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. It 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-(2-fluoro-4-methoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.60 g, 33%).

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-e438cd5c9fff4ae2b58442a950fdcb26
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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