Sulfuric Acid → 6-(2,6-dichloro-phenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one

HRID 11767Notes

Reaction equation

HRID 11767 reaction equation
CO[C:3](=[O:34])[CH:4]([C:26]1[C:31]([Cl:32])=[CH:30][CH:29]=[CH:28][C:27]=1[Cl:33])[CH2:5][C:6]1[C:7]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=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>[Cl:32][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:33])[C:26]=1[CH:4]1[C:3](=[O:34])[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:7]2[N:8]=[C:9]([NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:10]=[CH:11][C:6]=2[CH2:5]1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 210443273-(2,4-Diphenylamino-pyrimidin-5-yl)-2-(2,6-dichloro-phenyl)-propionic acid methyl ester

Product 1

HCID 100499356-(2,6-dichloro-phenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(2,6-dichloro-phenyl)-propionic acid methyl ester (0.18 g, 0.36 mmol) (from Example 2b supra) in glacial acetic acid (2 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 135° C. overnight and 145° C. for another 4 hours. After cooling, the reaction mixture was 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 to give the crude product which was crystallized from ethyl acetate-hexanes to give 6-(2,6-dichloro-phenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one as a gray solid. (Yield 61.2 mg, 36.3%).

Workup

  1. temperatureAfter cooling
  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. customto give the crude product which
  9. customwas crystallized from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-2ff6d305ccb84e36a219e0e4e3c0ef09
Source dataset
uspto-grants-2006_08
Patent number
US07098332B2

Reaction notes

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