Diethyl Ether → N-(3-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79392

Reaktionsgleichung

Reaktionsgleichung von HRID 79392
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][O:12][C:13]2[CH:18]=[CH:17][N:16]3[C:19]([C:22]([O-])=[O:23])=[CH:20][N:21]=[C:15]3[CH:14]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[Li+].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH:38]1([C:41]2[C:49]3[C:48]([NH2:50])=[CH:47][CH:46]=[CH:45][C:44]=3[N:43]([CH2:51][C:52]3[CH:56]=[CH:55][N:54]([CH2:57][CH3:58])[N:53]=3)[N:42]=2)[CH2:40][CH2:39]1.CCOCC>CN1C(=O)CCC1>[CH:38]1([C:41]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][C:48]=3[NH:50][C:22]([C:19]3[N:16]4[CH:17]=[CH:18][C:13]([O:12][CH2:11][CH2:10][N:7]5[CH2:8][CH2:9][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:5][CH2:6]5)=[CH:14][C:15]4=[N:21][CH:20]=3)=[O:23])[N:43]([CH2:51][C:52]3[CH:56]=[CH:55][N:54]([CH2:57][CH3:58])[N:53]=3)[N:42]=2)[CH2:39][CH2:40]1

Komponenten

6

Edukt 4

HCID 3283Diethyl EtherHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 672595033-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amineHCID 67260109Lithium 7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate

Produkt 1

HCID 67259888N-(3-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 75,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
88 °C

Versuchsvorschrift

To a solution of lithium 7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (531 mg, 1.57 mmol) in NMP (6 mL) at 0° C. was added 2,4,6-trichlorobenzoyl chloride (250 μL, 1.56 mmol). The cold bath was removed once the addition was complete. The mixture was stirred for a further 1 hour. 3-Cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (310 mg, 1.10 mmol; prepared as in Example 61, step E) was added and the reaction mixture was heated to 88° C. for 11 hours. The mixture was cooled to ambient temperature. Vacuum distillation was set up and NMP was removed until the reaction mixture became a thick oily residue, to which 10% NaOH aqueous solution (10 mL) was added and the resulting clear solution was stirred at 80° C. for 30 minutes. The solution was cooled to ambient temperature and extracted with DCM. The organic extracts were combined, dried (Na2SO4) and concentrated under vacuum to give a residual oil, which was triturates with Et2O (50 mL). The resulting solids were washed with Et2O (40 mL) to give the final product (492 mg). MS (ES+APCI) m/z=596 (M+H).

Aufarbeitung

  1. customThe cold bath was removed once the addition
  2. temperatureThe mixture was cooled to ambient temperature
  3. distillationVacuum distillation
  4. customNMP was removed until the reaction mixture
  5. additionto which 10% NaOH aqueous solution (10 mL) was added
  6. stirringthe resulting clear solution was stirred at 80° C. for 30 minutes
  7. temperatureThe solution was cooled to ambient temperature
  8. extractionextracted with DCM
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under vacuum
  11. customto give a residual oil, which
  12. washThe resulting solids were washed with Et2O (40 mL)

Quellen und Nachweise

ORD-Eintrag
ord-edc89a7b37da4f89a5e463922531f859
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

Verknüpfte Notizen

Wird geladen…