Pyrrolidine → HCID 59632261, Verbindung

HRID 2369094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2369094
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:21]=3)=[CH:16][C:15]=2[CH3:30])=[CH:12][C:11]([C:31]([O:33]C)=O)=[N:10]1.[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1>>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[N:9]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:21]=3)=[CH:16][C:15]=2[CH3:30])=[CH:12][C:11]([C:31]([N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[O:33])=[N:10]1

Komponenten

3

Edukt 2

HCID 31268PyrrolidineHCID 59632159HCID 59632159, Verbindung

Produkt 1

HCID 59632261HCID 59632261, VerbindungAusbeute 14 %

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

Methyl 1-(2,6-dichlorophenyl)-5-(3-methyl-3′-(methylsulfonyl)biphenyl-4-yl)-1H-pyrazole-3-carboxylate (102 mg, 0.20 mmol) was suspended in pyrrolidine (0.6 mL, 7.2 mmol) and heated in the microwave at 180° C. for 10 minutes. The dark reaction mixture was concentrated under reduced pressure and azeotroped with toluene to remove most of the pyrrolidine. The resulting crude product was purified by preparative reverse phase HPLC eluting with MeCN/H2O with 0.05% TFA. The product fractions from the HPLC were made basic by the careful addition of saturated aqueous NaHCO3. The resulting mixture was concentrated to remove most of the MeCN. The resulting aqueous suspension was extracted with CH2Cl2 (3×), and the combined extracts were dried over Na2SO4 overnight, filtered and concentrated under reduced pressure to afford (1-(2,6-dichlorophenyl)-5-(3-methyl-3′-(methylsulfonyl)biphenyl-4-yl)-1H-pyrazol-3-yl)(pyrrolidin-1-yl)methanone (15 mg, 14% yield) as a brown solid. 1H NMR (400 MHz CDCl3): δ 8.10 (1H, m), 7.91 (1H, m), 7.83 (1H, m), 7.62 (1H, t), 7.49 (1H, d), 7.42-7.34 (2H, m), 7.33-7.21 (2H, m), 7.13 (1H, d), 7.06 (1H, s), 3.99 (2H, t), 3.71 (2H, t), 3.08 (3H, s), 2.50 (3H, s), 2.03-1.86 (4H, m). MS(ES): 554 [M+H]+.

Aufarbeitung

  1. customThe dark reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. customazeotroped with toluene
  4. customto remove most of the pyrrolidine
  5. customThe resulting crude product was purified by preparative reverse phase HPLC
  6. washeluting with MeCN/H2O with 0.05% TFA
  7. additionThe product fractions from the HPLC were made basic by the careful addition of saturated aqueous NaHCO3
  8. concentrationThe resulting mixture was concentrated
  9. customto remove most of the MeCN
  10. extractionThe resulting aqueous suspension was extracted with CH2Cl2 (3×)
  11. dry with materialthe combined extracts were dried over Na2SO4 overnight
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-eecdd83e7b81474096df8e39b972c5d9
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703805B2

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