Dichloromethane → 7-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335268

Reaktionsgleichung

Reaktionsgleichung von HRID 335268
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)[CH:17]=[CH:16][C:15]=3[F:37])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[C:45](=[O:50])[NH:46][CH2:47][CH2:48][OH:49].C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>CN(C=O)C.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:38][C:39]1[CH:40]=[C:41]([C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]([NH:13][C:14]4[CH:19]=[C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)[CH:17]=[CH:16][C:15]=4[F:37])=[O:12])=[CH:9][N:10]=[C:4]3[CH:3]=2)[CH:42]=[CH:43][C:44]=1[C:45](=[O:50])[NH:46][CH2:47][CH2:48][OH:49]

Komponenten

9

Edukt 4

HCID 6344Dichloromethane2×HCID 10796Cesium carbonate2×HCID 44717645(3-Fluoro-4-((2-hydroxyethyl)carbamoyl)phenyl)boronic acid2×HCID 712830957-Bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Produkt 1

HCID 712834897-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator2×HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture comprising 7-bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (Ex 1.1, step 1) (120 mg, 0.212 mmol), 3-fluoro-4-(2-hydroxyethylcarbamoyl)phenylboronic acid (48.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) in DMF (3 ml) under N2 was heated at 85° C. for 2 hrs. Further portions of 3-fluoro-4-(2-hydroxyethylcarbamoyl)phenylboronic acid (48.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) were added and heating continued at 100° C. overnight. The reaction mixture was diluted with EtOAc and water and the biphasic mixture was filtered. The filtercake was washed with MeOH and the filtrate was concentrated under vacuum. Purification of the crude residue by chromatography on silica eluting with 0-20% NH3MeOH/DCM afforded a beige solid. The solid was triturated with THF/ether and dried in vacuo at 45° C. overnight to afford the title compound;

Aufarbeitung

  1. temperatureheating
  2. filtrationthe biphasic mixture was filtered
  3. washThe filtercake was washed with MeOH
  4. concentrationthe filtrate was concentrated under vacuum
  5. customPurification of the crude residue by chromatography on silica eluting with 0-20% NH3MeOH/DCM
  6. customafforded a beige solid
  7. customThe solid was triturated with THF/ether
  8. customdried in vacuo at 45° C. overnight

Quellen und Nachweise

ORD-Eintrag
ord-13c1f3bd6e6b47b9aca5b42eaaf0ed89
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883819B2

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