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 335281Notes

Reaction equation

HRID 335281 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
60 °C

Procedure

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;

Workup

  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

Sources & evidence

ORD record
ord-3f0a3266c4bd436396124fc4728186e8
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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