p-Toluenesulfonic acid → Balaglitazone

HRID 992732Notes

Reaction equation

HRID 992732 reaction equation
[C:1]([CH2:6][O:7][C:8]1[CH:21]=[CH:20][C:11]([CH2:12][CH:13]2[S:17][C:16](=[O:18])[NH:15][C:14]2=[O:19])=[CH:10][CH:9]=1)(OCC)=O.[CH3:22][NH:23][C:24](=[O:32])[C:25]1[C:26](=[CH:28][CH:29]=[CH:30][CH:31]=1)[NH2:27].C1(C)C(C)=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:22][N:23]1[C:24](=[O:32])[C:25]2[C:26](=[CH:28][CH:29]=[CH:30][CH:31]=2)[N:27]=[C:1]1[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:12][CH:13]2[S:17][C:16](=[O:18])[NH:15][C:14]2=[O:19])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7237O-XyleneHCID 3080722-Amino-N-methylbenzamideHCID 10852377Ethyl 2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]acetate

Product 1

HCID 9889200Balaglitazone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
175 °C

Procedure

A suspension of 5-[4-[(carboethoxy)methoxy]benzyl]thiazolidine-2,4-dione obtained by following a procedure described in any of Examples 16-22 (100 g, 0.32 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 10-15 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 (29 g, Y-23%, 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-08af8f16a8aa41c3b0acd38bd774ebbc
Source dataset
uspto-grants-2002_10
Patent number
US06469167B1

Reaction notes

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