p-Toluenesulfonic acid → HCID 59280184, compound

HRID 1913200Notes

Reaction equation

HRID 1913200 reaction equation
CN(C)[CH:3]=[C:4]([C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)[C:5](OCC)=[O:6].[C:17]([O:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([NH:29][NH2:30])=[N:27][CH:28]=1)([CH3:20])([CH3:19])[CH3:18].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[C:17]([O:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([N:29]2[C:5](=[O:6])[C:4]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)=[CH:3][NH:30]2)=[N:27][CH:28]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 59280221HCID 59280221, compoundHCID 687048643-(Dimethylamino)-2-pyridin-3-yl-acrylic acid ethyl ester

Product 1

HCID 59280184HCID 59280184, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

661 mg (3.0 mmol) of the compound from Example 2A and 586 mg (3.0 mmol) of the compound from Example 17A are initially charged in 10 ml of ethanol. 114 mg (0.6 mmol) of p-toluenesulfonic acid are added, and the mixture is stirred under reflux for 16 h. The mixture is then allowed to cool to RT, and the solid formed is filtered off, washed once with ethanol and dried under high vacuum. The solid is then stirred in tert-butyl methyl ether for 30 min, filtered off again and dried under high vacuum (batch 1). The filtrates and wash solutions obtained beforehand are combined and concentrated, and the residue is stirred in saturated sodium bicarbonate solution. The solid obtained is filtered off and washed once with water, and the filter residue is then purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA to the water). The product fractions are combined and concentrated (batch 2).

Workup

  1. temperatureunder reflux for 16 h
  2. customthe solid formed
  3. filtrationis filtered off
  4. washwashed once with ethanol
  5. customdried under high vacuum
  6. stirringThe solid is then stirred in tert-butyl methyl ether for 30 min
  7. filtrationfiltered off again
  8. customdried under high vacuum (batch 1)
  9. washThe filtrates and wash solutions
  10. customobtained beforehand
  11. concentrationconcentrated
  12. stirringthe residue is stirred in saturated sodium bicarbonate solution
  13. customThe solid obtained
  14. filtrationis filtered off
  15. washwashed once with water
  16. customthe filter residue is then purified by preparative HPLC (RP18 column
  17. additionmobile phase: acetonitrile/water gradient with addition of 0.1% TFA to the water)
  18. concentrationconcentrated (batch 2)

Sources & evidence

ORD record
ord-884ce43bf3d54d938d302cbfc058f329
Source dataset
uspto-grants-2013_12
Patent number
US08609698B2

Reaction notes

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