p-Toluenesulfonic acid → Balaglitazone

HRID 992728Notes

Reaction equation

HRID 992728 reaction equation
[C:1]([CH2:5][O:6][C:7]1[CH:20]=[CH:19][C:10]([CH2:11][CH:12]2[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])=[CH:9][CH:8]=1)(OC)=O.[CH3:21][NH:22][C:23](=[O:31])[C:24]1[C:25](=[CH:27][CH:28]=[CH:29][CH:30]=1)[NH2:26].C1(C)C(C)=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:21][N:22]1[C:23](=[O:31])[C:24]2[C:25](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:26]=[C:1]1[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][CH:12]2[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7237O-XyleneHCID 3080722-Amino-N-methylbenzamideHCID 235141985-(4-Methoxycarbonylmethyloxybenzyl)thiazolidine-2,4-dione

Product 1

HCID 9889200Balaglitazone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
175 °C

Procedure

A suspension of 5-[4-[(carbomethoxy)methoxy]benzyl]thiazolidine-2,4-dione obtained by following a procedure described in Example 23 or 24 (100 g, 0.34 M), N-methyl anthranilamide (58.7 g, 0.39 M), xylene (100 ml) and p-toluenesulfonic 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 45-55 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 (66 g, Y=49%, 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-c751708f5f4f4148abd68d79f57eb036
Source dataset
uspto-grants-2002_10
Patent number
US06469167B1

Reaction notes

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