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

HRID 79381

Reaktionsgleichung

Reaktionsgleichung von HRID 79381
[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-])=[O:21])=[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.[CH2:36]([C:38]1[C:46]2[C:45]([NH2:47])=[CH:44][CH:43]=[CH:42][C:41]=2[N:40]([CH2:48][C:49]2[CH:53]=[CH:52][N:51]([CH3:54])[N:50]=2)[N:39]=1)[CH3:37]>CN1C(=O)CCC1.[OH-].[Na+].CCOC(C)=O>[CH2:36]([C:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][C:45]=2[NH:47][C:20]([C:17]2[N:14]3[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:12][C:13]3=[N:19][CH:18]=2)=[O:21])[N:40]([CH2:48][C:49]2[CH:53]=[CH:52][N:51]([CH3:54])[N:50]=2)[N:39]=1)[CH3:37]

Komponenten

7

Edukt 3

HCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67252742Lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672599453-ethyl-1-((1-methyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine

Produkt 1

HCID 67260125N-(3-ethyl-1-((1-methyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 66,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
87 °C

Versuchsvorschrift

To a suspension of lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (94.0 mg, 0.294 mmol) (Example 56, step A) in NMP (4 mL) was added 2,4,6-trichlorobenzoyl chloride (45.9 μL, 0.294 mmol). The reaction mixture was stirred for 30 minutes. 3-Ethyl-1-((1-methyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (50 mg, 0.196 mmol) was added and the mixture was heated at 87° C. for 3 hours. The mixture was cooled to ambient temperature and diluted with 10% NaOH aqueous solution (5 mL) and EtOAc. The organic phase was washed with water and brine, concentrated under reduced pressure and the residue was triturated with Et2O to give the final product (71 mg). MS (ES+APCI) m/z=542 (M+H).

Aufarbeitung

  1. temperatureThe mixture was cooled to ambient temperature
  2. washThe organic phase was washed with water and brine
  3. concentrationconcentrated under reduced pressure
  4. customthe residue was triturated with Et2O

Quellen und Nachweise

ORD-Eintrag
ord-27d8cad7eea5470f956803bfcf5fb177
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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