p-Toluenesulfonic acid → Balaglitazone

HRID 992725Notes

Reaction equation

HRID 992725 reaction equation
[C:1]([CH2:4][O:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:8][CH:7]=1)(O)=O.[CH3:20][NH:21][C:22](=[O:30])[C:23]1[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=1)[NH2:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:20][N:21]1[C:22](=[O:30])[C:23]2[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:25]=[C:1]1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 3080722-Amino-N-methylbenzamideHCID 113234852-(4-((2,4-Dioxothiazolidin-5-YL)methyl)phenoxy)acetic acid

Product 1

HCID 9889200Balaglitazone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
175 °C

Procedure

A suspension of 5-[4-[(carboxy)methoxy]benzyl]thiazolidine-2-4-dione obtained by following a procedure described in any of Examples 25-28 (100 g, 0.356 M), N-methyl anthranilamide (58.7 g, 0.391 M), and p-toluenesulphonic acid (200 mg) was taken in a round bottom flask fitted with a mechanical stirrer, oil bath and Dean-Stark condenser. The reaction mixture was heated to reflux (internal temperature 150-155° C., oil bath temperature 170-180° C.) for a period of 12-15 h while monitoring the reaction by TLC. After completion of the reaction, the reaction mass was cooled to 80° C. and methanol (700 ml) was added slowly through a dropping funnel. The reaction mass was allowed to attain room temperature while stirring and the solid thus obtained was filtered and washed with methanol (150 ml) and dried at 100-120° C. for 1 h to afford 5-[4-[[3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]methoxy]benzyl]thiazolidine-2,4-dione as a white solid (100 g , Y=71%, P=98%).

Workup

  1. customobtained
  2. customwas taken in a round bottom flask
  3. customfitted with a mechanical stirrer, oil bath
  4. temperatureThe reaction mixture was heated
  5. customthe reaction by TLC
  6. customAfter completion of the reaction
  7. temperaturethe reaction mass was cooled to 80° C.
  8. customto attain room temperature
  9. customthe solid thus obtained
  10. filtrationwas filtered
  11. washwashed with methanol (150 ml)
  12. customdried at 100-120° C. for 1 h

Sources & evidence

ORD record
ord-caa81dccaef648a8818bb7540a795add
Source dataset
uspto-grants-2002_10
Patent number
US06469167B1

Reaction notes

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