Sulfuric Acid → 8-cyclopropylmethyl-6-(4-methoxy-phenyl)-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidine-7-one

HRID 11798Notes

Reaction equation

HRID 11798 reaction equation
C[O:2][C:3](=O)[CH:4]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[CH2:5][C:6]1[C:7]([NH:19][CH2:20][CH:21]2[CH2:23][CH2:22]2)=[N:8][C:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:10][CH:11]=1.S(=O)(=O)(O)O>C(O)(=O)C.C(OCC)(=O)C>[CH:21]1([CH2:20][N:19]2[C:7]3[N:8]=[C:9]([NH:12][C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:10]=[CH:11][C:6]=3[CH2:5][CH:4]([C:24]3[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=3)[C:3]2=[O:2])[CH2:23][CH2:22]1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 210443193-(2-Phenylamino-4-cyclopropylmethylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester

Product 1

HCID 99783418-cyclopropylmethyl-6-(4-methoxy-phenyl)-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidine-7-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of crude 3-(2-phenylamino-4-cyclopropylmethylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (51.3 mg) (from Example 14a supra) in glacial acetic acid (1 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 85° C. for 3 hours. The reaction mixture was cooled, diluted with ethyl acetate (50 mL) and quenched with 2 N aqueous sodium hydroxide solution. The organic layer was separated and successively washed with water (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative thin layer chromatography to give 8-cyclopropylmethyl-6-(4-methoxy-phenyl)-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidine-7-one as a light yellow amorphous solid. (Yield 6.7 mg, 14.8%, 2 steps).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with 2 N aqueous sodium hydroxide solution
  3. customThe organic layer was separated
  4. washsuccessively washed with water (10 mL) and brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-4c05c88a2a714ca08093234ae20c2763
Source dataset
uspto-grants-2006_08
Patent number
US07098332B2

Reaction notes

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