Methanesulfonic Acid → benzyl 4-(1-(pyridin-2-yl)-1H-pyrazol-5-yl)piperazine-1-carboxylate

HRID 1157804Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157804
C(O[CH:4](OCC)[CH2:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][CH2:9]1)=O)C.FC(F)(F)C(O)=O.[NH:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)[NH2:35].CS(O)(=O)=O.P(Cl)(Cl)(Cl)=O>C(Cl)(Cl)Cl.N1C=CC=CC=1.O>[N:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[N:34]1[C:6]([N:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:15])[CH2:12][CH2:13]2)=[CH:5][CH:4]=[N:35]1

Komponenten

9

Edukt 5

HCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 24813Phosphorus oxychlorideHCID 786452-HydrazinopyridineHCID 23014298Benzyl 4-(3,3-diethoxypropanoyl)piperazine-1-carboxylate

Produkt 1

HCID 68693775benzyl 4-(1-(pyridin-2-yl)-1H-pyrazol-5-yl)piperazine-1-carboxylateAusbeute 11,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittelHCID 6212ChloroformLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Part B: To a solution of benzyl 4-(3,3-diethoxypropanoyl)piperazine-1-carboxylate (3.39 g, 9.30 mmol) in 30 mL of chloroform at 0° C. was added a solution of 10.0 mL of water and 10.0 mL of trifluoroacetic acid, and the resulting biphasic mixture was stirred at 25° C. for 20 h. The mixture then was diluted with additional chloroform, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue then was dissolved in 50 mL of ethanol. To this solution was added 2-hydrazinopyridine (1.015 g, 9.30 mmol) and methanesulfonic acid (0.060 mL, 0.930 mmol), and the resulting mixture was stirred at 25° C. for 18 h. Pyridine (1.00 mL) was added, and then the reaction mixture was concentrated under vacuum. The residue was dissolved in 50 mL of pyridine. To this solution was added phosphorous oxychloride (1.73 mL, 18.6 mmol), and the mixture was stirred at 25° C. for 20 h. The mixture was concentrated under vacuum. The residue was diluted with water and ethyl acetate, and the phases were separated. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (elution: 10-50% ethyl acetate/methylene chloride) afforded 0.38 g (11.2%) of benzyl 4-(1-(pyridin-2-yl)-1H-pyrazol-5-yl)piperazine-1-carboxylate as an oil; Mass Spec.: m/e: 364.20 (M+H)+ [calc'd: 364.18]; 1H NMR (500 MHz, DMSO-D6) δ 8.53 (d, 1H, J=5.0 Hz), 7.97 (t, 1H, J=8.0 Hz), 7.73 (d, 1H, J=8.0 Hz), 7.58 (s, 1H), 7.40-7.30 (m, 6H), 6.04 (s, 1H), 5.10 (s, 2H), 3.49 (m, 4H), 2.94 (m, 4H).

Aufarbeitung

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue then was dissolved in 50 mL of ethanol
  6. stirringthe resulting mixture was stirred at 25° C. for 18 h
  7. concentrationthe reaction mixture was concentrated under vacuum
  8. dissolutionThe residue was dissolved in 50 mL of pyridine
  9. stirringthe mixture was stirred at 25° C. for 20 h
  10. concentrationThe mixture was concentrated under vacuum
  11. additionThe residue was diluted with water and ethyl acetate
  12. customthe phases were separated
  13. washThe organic phase was washed with water and brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-c77d592b27e344999333046974fbd88f
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807676B2

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