p-Toluenesulfonic acid → HCID 135979570, compound

HRID 1782171Notes

Reaction equation

HRID 1782171 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]([NH2:10])=[O:9].[C:11]1([CH3:21])[CH:16]=CC(S(O)(=O)=O)=[CH:13][CH:12]=1.CN(C=O)C.C(=O)CC(C)C>C1(C)C=CC=CC=1>[CH2:12]([C:13]1[NH:10][C:8](=[O:9])[C:3]2[C:4]([CH3:7])=[N:5][S:6][C:2]=2[N:1]=1)[CH:11]([CH3:21])[CH3:16]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6228DimethylformamideHCID 115523-MethylbutanalHCID 122550895-AMINO-3-METHYLISOTHIAZOLE-4-CARBOXAMIDE

Product 1

HCID 135979570HCID 135979570, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a 2 L flask equipped with Dean Stark was charged 5-amino-3-methylisothiazole-4-carboxamide (method 63) (1 equiv), p-toluene sulphonic acid (0.049 equiv), DMF (9.75 volumes). The reaction was stirred until a solution was obtained and isovaleraldehyde (1.10 equiv) and toluene (4.9 volumes) were added. The resulting mixture was heated to 130° C. and held at reflux for 1 hour removing water via a Dean Stark apparatus. Once the reaction was complete toluene was removed under vacuum distillation. Sodium bisullfite (2.50 equiv) was charged and the mixture was held at 115° C. for 7 hours, then cooled to room temperature overnight. The solid was removed by filtration through harborlite and washed with DMF (1 volume). Analysis showed conversion to product and the reaction was heated to 50° C., water (15 volumes) was added and the resulting precipitate was cooled to room temperature and held for 1 h. The product was isolated by filtration and washed with water (2×0.5 volumes), dried to give a pale brown solid (typical yield 89%).

Workup

  1. customTo a 2 L flask equipped with Dean Stark
  2. customwas obtained
  3. temperatureat reflux for 1 hour
  4. customremoving water via a Dean Stark apparatus
  5. customwas removed under vacuum distillation
  6. additionSodium bisullfite (2.50 equiv) was charged
  7. temperaturecooled to room temperature overnight
  8. customThe solid was removed by filtration through harborlite
  9. washwashed with DMF (1 volume)
  10. temperaturethe reaction was heated to 50° C.
  11. additionwater (15 volumes) was added
  12. temperaturethe resulting precipitate was cooled to room temperature
  13. waitheld for 1 h
  14. customThe product was isolated by filtration
  15. washwashed with water (2×0.5 volumes)
  16. customdried
  17. customto give a pale brown solid (typical yield 89%)

Sources & evidence

ORD record
ord-eb0c0b8467484fba9b96596c5fbc15c7
Source dataset
uspto-grants-2009_03
Patent number
US07498333B2

Reaction notes

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