Picolinoyl Chloride Hydrochloride → HCID 136333926, compound

HRID 1426438Notes

Reaction equation

HRID 1426438 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([Br:7])[S:4][C:3]=1[C:8]([NH2:10])=[O:9].Cl.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18](Cl)=O.C(=O)([O-])O.[Na+]>C(N(CC)CC)C.O1CCCC1>[Br:7][C:5]1[S:4][C:3]2[C:8](=[O:9])[NH:10][C:18]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=3)=[N:1][C:2]=2[CH:6]=1

Participants

6

Reactant 3

HCID 135033Picolinoyl Chloride Hydrochloride2×HCID 516892Sodium BicarbonateHCID 219758623-Amino-5-bromothiophene-2-carboxamide

Product 1

HCID 136333926HCID 136333926, compoundYield 97.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

To a mixture of 3-amino-5-bromothiophene-2-carboxamide (221 mg) produced in Example 1, step D, triethylamine (0.42 mL) and tetrahydrofuran (15 mL) was added pyridine-2-carbonylchloride hydrochloride (214 mg) with stirring at room temperature. The mixture was stirred at room temperature for 30 min and at 50° C. overnight. Triethylamine (0.42 mL) and pyridine-2-carbonylchloride hydrochloride (214 mg) were added to the reaction mixture. 2 hr later, aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The separated organic layer was washed with water and brine (5 mL), and dried over anhydrous magnesium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. Ethanol (10 mL) and 2M aqueous sodium hydroxide solution (3.0 mL) were added to the residue, and the mixture was stirred at 80° C. for 1 hr. The reaction mixture was neutralized with 6M hydrochloric acid under ice-cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine (10 mL), and dried over anhydrous magnesium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give a crude product (300 mg) of the title compound as a pale-orange solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 30 min and at 50° C. overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe separated organic layer was washed with water and brine (5 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationInsoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. additionEthanol (10 mL) and 2M aqueous sodium hydroxide solution (3.0 mL) were added to the residue
  8. stirringthe mixture was stirred at 80° C. for 1 hr
  9. temperaturecooling
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with brine (10 mL)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationInsoluble material was filtered off
  14. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-56d88d57643d43ad9b4591805ef1aeac
Source dataset
uspto-grants-2015_01
Patent number
US08933069B2

Reaction notes

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