3-Amino-2,2-dimethylpropanamide → {(1S,2S,4S)-4-(2-Carbamoyl-2-methylpropylcarbamoyl)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

Temperature

80 °C

140 mg of 3-amino-2,2-di(methyl)propionamide obtained in Reference Example 2 (1.21 mmol) and 38 mg of 2-hydroxypyridine (0.40 mmol) were added to a solution of 205 mg of {(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (1m) (0.40 mmol) in triethylamine (4 ml), and the mixture was stirred at 80° C. for four hours. The reaction mixture was cooled and then concentrated under reduced pressure and further stirred at 80° C. for 14 hours. The reaction mixture was cooled and then water was added, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=40/3) to obtain 167 mg of the title compound (yield: 66%).

1. temperatureThe reaction mixture was cooled
2. concentrationconcentrated under reduced pressure
3. stirringfurther stirred at 80° C. for 14 hours
4. temperatureThe reaction mixture was cooled
5. additionwater was added
6. extractionfollowed by extraction with methylene chloride
7. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
8. filtrationAfter filtration
9. customthe solvent was evaporated under reduced pressure
10. customthe residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=40/3)

ORD record

ord-b87bd1c3f4254bfaa2dab21a7cc04493

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158790B2