Hydrochloric Acid → N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride

HRID 354099Notes

Reaction equation

HRID 354099 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]([O:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[N:21][CH:22]=[C:23]([F:25])[CH:24]=2)=[O:18])=[CH:11][CH:10]=1)(C)(C)C.[ClH:35]>CO>[ClH:35].[NH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17](=[O:18])[C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[N:21][C:20]=2[O:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 20738636[4-({[5-Fluoro-2-(4-fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

Product 1

HCID 23512939N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[4-({[5-Fluoro-2-(4-fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (1.62 g, 3.44 mmol) (see Preparation 5) was dissolved in a 2.25 M solution of hydrochloric acid in methanol (100 ml) and the mixture stirred at room temperature under an atmosphere of nitrogen for 4 hours before removing the solvent in vacuo. The residue was dissolved in water (50 ml), the pH adjusted to pH higher than 8 by addition of sodium hydrogen carbonate and extracted with dichloromethane (3-fold 50 ml). The combined organic extracts were dried over anhydrous magnesium sulphate and concentrated in vacuo to give N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride (1.25 mg) as a gum.

Workup

  1. custombefore removing the solvent in vacuo
  2. dissolutionThe residue was dissolved in water (50 ml)
  3. additionto pH higher than 8 by addition of sodium hydrogen carbonate
  4. extractionextracted with dichloromethane (3-fold 50 ml)
  5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulphate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1213500b4e044f2e9d6bf8eee3c2b78a
Source dataset
uspto-grants-2004_06
Patent number
US06756392B2

Reaction notes

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