Piperazine → HCID 19734362, compound

HRID 326989Notes

Reaction equation

HRID 326989 reaction equation
C([C:5]1[S:13][C:8]2=[CH:9][N:10]=[CH:11][CH:12]=[C:7]2[C:6]=1[NH2:14])(OC)=O.[NH:15]1[CH2:20][CH2:19]N[CH2:17][CH2:16]1>CN1CCCC1=O.O>[N:14]1([C:6]2[C:7]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[S:13][CH:5]=2)[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]1

Participants

5

Reactant 2

HCID 4837PiperazineHCID 2764765Methyl 3-aminothieno[2,3-c]pyridine-2-carboxylate

Product 1

HCID 19734362HCID 19734362, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-carbomethoxy-3-aminothieno[2,3-c]pyridine (5.0 g), and piperazine (4.13 g) in N-methylpyrrolidinone (30 ml) was heated to 150° until decarboxyalkylation was complete. The mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residual 3-aminothieno[2,3-c]pyridine, piperazine (12.5 g), p-toluenesulfonic acid (100 mg), and N-methylpyrrolidinone (50 ml) was heated under reflux (202°) overnight. The mixture was allowed to cool to room temperature, diluted with water, and extracted with dichloromethane. The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated in vacuo, finally at 50° (0.1 mm Hg). The residue was chromatographed on silica, using 1:1 dichloromethane:methanol eluent. The appropriate fractions were combined and concentrated. Crystallization of the residue from ethyl acetate provided 0.66 g (12%) of product, mp 126°-127.5° (dried 80° 0.1 mm Hg).

Workup

  1. temperaturewas heated to 150° until decarboxyalkylation
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated in vacuo
  6. temperatureThe residual 3-aminothieno[2,3-c]pyridine, piperazine (12.5 g), p-toluenesulfonic acid (100 mg), and N-methylpyrrolidinone (50 ml) was heated
  7. temperatureunder reflux (202°) overnight
  8. temperatureto cool to room temperature
  9. additiondiluted with water
  10. extractionextracted with dichloromethane
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated in vacuo, finally at 50° (0.1 mm Hg)
  14. customThe residue was chromatographed on silica
  15. concentrationconcentrated
  16. customCrystallization of the residue from ethyl acetate
  17. customprovided
  18. dry with material0.66 g (12%) of product, mp 126°-127.5° (dried 80° 0.1 mm Hg)

Sources & evidence

ORD record
ord-d12e43169c5c48d1b749603fc635c0f8
Source dataset
uspto-grants-1993_12
Patent number
US05272148

Reaction notes

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