Hydrochloric Acid → HCID 68818290, Verbindung

HRID 734357

Reaktionsgleichung

Reaktionsgleichung von HRID 734357
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C1(C2C=C(F)[CH:24]=[CH:23][C:22]=2[C:28]([C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32][C:31]=2C2CC2)=[O:29])CC1.C(=O)([O-])[O-].[K+].[K+].[ClH:46]>CS(C)=O.CO.C(OCC)C>[ClH:46].[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:13][CH2:14][N:15]([C:33]3[CH:32]=[CH:31][C:30]([C:28]([CH:22]4[CH2:23][CH2:24]4)=[O:29])=[CH:35][CH:34]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 28282195HCID 28282195, VerbindungHCID 53737258Cyclopropyl-4-fluorophenyl ketone

Produkt 1

HCID 68818290HCID 68818290, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 887MethanolLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To 1-isopropyl-4-(piperidine-4-carbonyl)-piperazine (D1)(0.25 g) and cyclopropyl-4-fluorophenyl ketone (0.3 g), dissolved in DMSO (5 ml) was added potassium carbonate (0.37 g). The reaction was heated to 140° C. for 2 h. After cooling the mixture, the inorganics were filtered off. The filtrate was diluted with MeOH (20 ml) and then poured onto a 10 g isolute SCX column which was washed with MeOH (50 ml). The product was eluted with 10% ammonia in MeOH (50 ml), and then further purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. Fractions containing the required product were evaporated to give the free base which was dissolved in MeOH (4 ml) and treated with 1N HCl in diethyl ether (2 ml) to give the title compound (E105) as a solid (51mg). 1H NMR δ [DMSO-d6]: 0.93 (4H, m) 1.27 (6H, d, J=6.4 Hz), 1.5-1.8 (2H, m), 2.77-3.14 (7H, m), 3.38-3.48 (2H, m), 3.92-4.56 (4H, m), 6.98 (2H, d, J=9.2 Hz), 7.89 (2H, d, J=9.2 Hz), 10.6 (1H, br s). MS electrospray; (+ve ion) 384 (MH+).

Aufarbeitung

  1. temperatureAfter cooling the mixture
  2. filtrationthe inorganics were filtered off
  3. additionThe filtrate was diluted with MeOH (20 ml)
  4. additionpoured onto a 10 g isolute SCX column which
  5. washwas washed with MeOH (50 ml)
  6. washThe product was eluted with 10% ammonia in MeOH (50 ml)
  7. customfurther purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  8. additionFractions containing the required product
  9. customwere evaporated
  10. customto give the free base which

Quellen und Nachweise

ORD-Eintrag
ord-fc9e64f6dc854addb070e413361ddf48
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07592347B2

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