Hydroxyphenylacetic acid → Nicotinamide

Exo-N-(8-aza-bicyclo[3.2.1]oct-3-yl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide (310 mg, 0.86 mmol, see Preparation 35) was added to 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (185 mg, 0.95 mmol), 4-hydroxyphenylacetic acid (134 mg, 0.86 mmol) and 1-hydroxybenzotriazole hydrate (128 mg, 0.95 mmol) in dichloromethane (5 ml) containing 4-methylmorpholine (104 μl, 0.95 mmol) and the mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with water and the organic phase was concentrated in-vacuo and then purified by chromatography on silica gel using methanol in dichloromethane containing ammonium hydroxide solution as eluant (gradient from 1:99:0.1 to 5:95:0.5). The material obtained was triturated with methanol and isolated by filtration then dried in-vacuo to give exo-5-fluoro-2-(4-fluoro-phenoxy)-N-8-[2-(4-hydroxy-phenyl)-acetyl]-8-aza-bicyclo[3.2.1]oct-3-yl}-nicotinamide (270 mg).

1. concentrationthe organic phase was concentrated in-vacuo
2. custompurified by chromatography on silica gel
3. additioncontaining ammonium hydroxide solution as eluant (gradient from 1:99:0.1 to 5:95:0.5)
4. customThe material obtained
5. customwas triturated with methanol
6. customisolated by filtration
7. customthen dried in-vacuo

ORD record

ord-566f869265d946269f2b7d3cb64cbf21

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949573B2