2,4,6-Trichlorobenzoyl chloride → N-(3-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79389

Reaktionsgleichung

Reaktionsgleichung von HRID 79389
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:20]([O-:22])=O)=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH2:4][CH2:3]1.[Li+].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH:36]1([C:39]2[C:47]3[C:46]([NH2:48])=[CH:45][CH:44]=[CH:43][C:42]=3[N:41]([CH2:49][C:50]3[CH:54]=[CH:53][N:52]([CH2:55][CH3:56])[N:51]=3)[N:40]=2)[CH2:38][CH2:37]1>CN1C(=O)CCC1>[CH:36]1([C:39]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][C:46]=3[NH:48][C:20]([C:17]3[N:14]4[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[CH:12][C:13]4=[N:19][CH:18]=3)=[O:22])[N:41]([CH2:49][C:50]3[CH:54]=[CH:53][N:52]([CH2:55][CH3:56])[N:51]=3)[N:40]=2)[CH2:37][CH2:38]1

Komponenten

5

Edukt 3

HCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67252742Lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672595033-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine

Produkt 1

HCID 67259527N-(3-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 66,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (100 mg, 0.316 mmol; prepared as in Example 56, step A) was added NMP (60 mL). The reaction mixture was cooled to 0° C. and 2,4,6-trichlorobenzoyl chloride (50.4 μL, 0.316 mmol) was added dropwise. The cold bath was removed once the addition was complete. The reaction mixture was stirred for 1 hour. The reaction mixture became cloudy. 3-Cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (59.4 mg, 0.211 mmol) was added and the 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 (100 mL) was added and the resulting clear solution was stirred at 80° C. for 30 minutes. The mixture was cooled to ambient temperature and extracted with DCM. The organic phases were combined, dried (Na2SO4) and concentrated under vacuum (bath temperature at 80° C. to remove left over NMP) to a thick residue, which was triturated with Et2O (500 mL) to give the final product (80 mg). MS (ES+APCI) m/z=568 (M+H).

Aufarbeitung

  1. customThe cold bath was removed once the addition
  2. temperaturethe mixture was heated to 88° C. for 11 hours
  3. temperatureThe mixture was cooled to ambient temperature
  4. distillationVacuum distillation
  5. customNMP was removed until the reaction mixture
  6. additionto which 10% NaOH aqueous solution (100 mL) was added
  7. stirringthe resulting clear solution was stirred at 80° C. for 30 minutes
  8. temperatureThe mixture was cooled to ambient temperature
  9. extractionextracted with DCM
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under vacuum (bath temperature at 80° C. to remove left over NMP) to a thick residue, which
  12. customwas triturated with Et2O (500 mL)

Quellen und Nachweise

ORD-Eintrag
ord-b5e98291355c4dc08c1b5dc2c90e898f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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