Betahistine → n-Methyl-n{(1r)-1-[n-methyl-n-(2-(2-pyridyl)ethyl)carbamoyl]-2-phenylethyl}carbamic acid tert-butyl ester

(2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-phenylpropionic acid (11.2 g, 40 mmol), 1-hydroxy-7-azabenzotriazole (5.4 g, 40 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (7.7 g, 40 mmol) were dissolved in dichloromethane (100 mL). The reaction mixture was stirred for 15 min. Ethyidiisopropylamine (6.85 mL, 40 mmol) and 2-(2-methylaminoethyl)pyridine (5.54 mL, 40 mmol) were added. The reaction mixture was stirred for 16 h. The reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (3×150 mL). The organic layer was dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate as eluent, to give 10.9 g of N-methyl-N{(1R)-1-[N-methyl-N-(2-(2-pyridyl)ethyl)carbamoyl]-2-phenylethyl}carbamic acid tert-butyl ester.

1. stirringThe reaction mixture was stirred for 16 h
2. washThe reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (3×150 mL)
3. dry with materialThe organic layer was dried over magnesium sulfate
4. customThe solvent was removed in vacuo
5. customThe crude product was purified by flash chromatography on silica (400 g)

ORDレコード

ord-09847c81757d4d2c9cececfcd3ced5ab

出典データセット

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06566337B1