Aniline → HCID 11212557, compound

HRID 1243160Notes

Reaction equation

HRID 1243160 reaction equation
Cl[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.[CH:24]1([N:30]=[C:31]=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[NH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>O1CCCC1.CN(C)C1C=CN=CC=1>[CH:24]1([N:30]2[C:6]3=[N:7][C:2]([NH:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[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:31]2=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 6115AnilineHCID 18502Cyclohexyl isocyanateHCID 21939303[(2,4-Dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amineHCID 178418339Butyllithium

Product 1

HCID 11212557HCID 11212557, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of [(2,4-dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine (200 mg, 0.70 mmol) (from Example 1d supra) in anhydrous tetrahydrofuran (24 mL) was treated with n-butyllithium (1.6 M solution in hexanes, 0.53 mL, 0.84 mmol) (Aldrich) at −78° C. This was followed by addition of cyclohexyl isocyanate (90 μL, 88 mg, 0.70 mmol) (Aldrich). The resulting mixture was stirred and slowly warmed up to room temperature within a period of 2 hours. The reaction mixture was then partitioned between ethyl acetate and brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by chromatography with a silica gel column using a 0–60% ethyl acetate in hexanes gradient. The intermediate that was obtained from this purification was dissolved in aniline (2 mL) (Aldrich), a catalytic amount of 4-(dimethylamino)pyridine (Aldrich) was added and the mixture was then heated at 100° C. After stirring overnight the mixture was cooled, and purified by silica gel column chromatography with a 0–60% ethyl acetate in hexanes gradient. The solid obtained from this purification was dissolved in tetrahydrofuran and then precipitated with excess of pentane to give 1-cyclohexyl-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a beige solid. (Yield 78 mg, 26%).

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and brine
  2. customThe organic layer was collected
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a residue that
  6. customwas purified by chromatography with a silica gel column
  7. customThe intermediate that was obtained from this purification
  8. temperaturethe mixture was then heated at 100° C
  9. stirringAfter stirring overnight the mixture
  10. temperaturewas cooled
  11. custompurified by silica gel column chromatography with a 0–60% ethyl acetate in hexanes gradient
  12. customThe solid obtained from this purification
  13. customprecipitated with excess of pentane

Sources & evidence

ORD record
ord-ce4faec314914e8d9f40e5b3dff8f0e2
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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