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Hydrochloric Acid → N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide Hydrochloride

HRID 335281
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 335281
[N:1]1([CH2:6][CH2:7][OH:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[Cl:11][C:12]1[N:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]3[C:24]([C:27]([NH:29][C:30]4[CH:35]=[C:34]([C:36](=[O:47])[NH:37][CH2:38][C:39]5[CH:44]=[CH:43][C:42]([F:45])=[C:41]([F:46])[CH:40]=5)[CH:33]=[CH:32][C:31]=4[F:48])=[O:28])=[CH:25][N:26]=[C:20]3[CH:19]=2)=[CH:14][CH:13]=1.Cl>C1(C)C=CC=CC=1.CO.C(OCC)C>[ClH:11].[F:46][C:41]1[CH:40]=[C:39]([CH:44]=[CH:43][C:42]=1[F:45])[CH2:38][NH:37][C:36]([C:34]1[CH:33]=[CH:32][C:31]([F:48])=[C:30]([NH:29][C:27]([C:24]2[N:21]3[CH:22]=[CH:23][C:18]([C:15]4[CH:16]=[N:17][C:12]([O:8][CH2:7][CH2:6][N:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)=[CH:13][CH:14]=4)=[CH:19][C:20]3=[N:26][CH:25]=2)=[O:28])[CH:35]=1)=[O:47]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 313Hydrochloric Acid2×HCID 24758Sodium hydrideHCID 762881-PyrrolidineethanolHCID 866956757-(6-Chloropyridin-3-yl)-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide

Produkt 1

HCID 71283374
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide Hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 2-(pyrrolidin-1-yl)ethanol (30.5 mg, 0.265 mmol) and sodium hydride (6.36 mg, 0.265 mmol) in toluene (442 μl) was stirred at RT for 30 mins and treated with 7-(6-chloropyridin-3-yl)-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (step 1). The reaction mixture was heated at 60° C. for 1 hour and the reaction was quenched with wet MeOH. Purification of the mixture by chromatography on silica eluting with 0-20% (2M NH3 in MeOH)/DCM afforded a yellow solid. The solid was dissolved in MeOH and treated with 2M HCl in diethyl ether (1 eq). The solvent was removed in vacuo and purification of the crude product by chromatography on silica eluting with 2M NH3 in MeOH/TBME afforded a solid. The solid was treated again with 2M HCl in diethyl ether and concentrated in vacuo to afford the title compound;

Aufarbeitung

  1. customthe reaction was quenched with wet MeOH
  2. customPurification of the mixture by chromatography on silica eluting with 0-20% (2M NH3 in MeOH)/DCM
  3. customafforded a yellow solid
  4. customThe solvent was removed in vacuo and purification of the crude product by chromatography on silica eluting with 2M NH3 in MeOH/TBME
  5. customafforded a solid
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-3f0a3266c4bd436396124fc4728186e8
Quelldatensatz
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08883819B2

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