Tetrahydrofuran → tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate

Hydroxylamine hydrochloride (35 mg) was dissolved in THF (3 ml)-methanol (3 ml), triethylamine (0.07 ml) was added, and the mixture was stirred at room temperature for 1 hr. A solution of tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(2H-tetrazol-5-yl)piperidine-1-carboxylate (120 mg) in THF (3 ml) was further added, and the mixture was stirred at 60° C. for 3 hr. The reaction mixture was allowed to cool to room temperature, and diluted with water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 ml). 1,1′-Carbonylbis(1H-imidazole) (72 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 ml) were added and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with 0.5 M hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography. The fraction eluted with ethyl acetate-hexane (10:95) to ethyl acetate was concentrated under reduced pressure to give the object compound (26.1 mg).

1. additionwas added
2. stirringthe mixture was stirred at 60° C. for 3 hr
3. temperatureto cool to room temperature
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialThe extract was dried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionthe residue was dissolved in tetrahydrofuran (5 ml)
8. addition1,1′-Carbonylbis(1H-imidazole) (72 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 ml) were added
9. stirringthe mixture was stirred at room temperature for 30 min
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. additiondiluted with ethyl acetate
12. washwashed with 0.5 M hydrochloric acid and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationThe solution was concentrated under reduced pressure
15. washThe fraction eluted with ethyl acetate-hexane (10:95) to ethyl acetate
16. concentrationwas concentrated under reduced pressure

ORDレコード

ord-a7be39d84c68493eb4f37c773af1a13f

出典データセット

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08329691B2