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

HRID 79399

Reaktionsgleichung

Reaktionsgleichung von HRID 79399
[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]([CH:57]([CH3:59])[CH3:58])[N:53]=3)[N:42]=2)[CH2:40][CH2:39]1.[OH-].[Na+]>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]([CH3:3])[CH3:2])[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]([CH:57]([CH3:59])[CH3:58])[N:53]=3)[N:42]=2)[CH2:39][CH2:40]1

Komponenten

6

Edukt 4

HCID 14798Sodium HydroxideHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67260109Lithium 7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672610713-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine

Produkt 1

HCID 67261334N-(3-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-isopropylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 61,1 %

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 (123 mg, 0.364 mmol; prepared according to Example 62, Step B) in NMP (10 mL) at 0° C. was added 2,4,6-trichlorobenzoyl chloride (57.9 μL, 0.363 mmol). The cold bath was removed once the addition was complete. The mixture was stirred for one hour. 3-Cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (80 mg, 0.271 mmol; prepared according to Example 63, step E) was added and the reaction mixture was heated at 88° C. for 11 hours. The reaction mixture was cooled to ambient temperature, and NMP was removed under reduced pressure to give an oily residue. To this was added 10% NaOH aqueous solution (10 mL) 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 combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to give a residue, which was triturated with Et2O (50 mL). The resulting solids were isolated by filtration, washed with ether and dried under vacuum to give the product (101 mg). MS (ES+APCI) m/z=610 (M+H).

Aufarbeitung

  1. customThe cold bath was removed once the addition
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customNMP was removed under reduced pressure
  4. customto give an oily residue
  5. stirringthe resulting clear solution was stirred at 80° C. for 30 minutes
  6. temperatureThe solution was cooled to ambient temperature
  7. extractionextracted with DCM
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customto give a residue, which
  11. customwas triturated with Et2O (50 mL)
  12. customThe resulting solids were isolated by filtration
  13. washwashed with ether
  14. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e50e9b6c00a44aa8b0613bb82a79604c
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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