Hydrogen Peroxide → 4-(4-(6-chloro-2-(((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-1H-imidazo[4,5-b]pyridin-5-yl)phenyl)-3-hydroxytetrahydro-2H-thiopyran 1,1-dioxide

To a stirred solution of 4-(4-(2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-5-yl)phenyl)-3,6-dihydro-2H-thiopyran 1,1-dioxide (50 mg, 0.067 mmol) under nitrogen in anhydrous THF (0.7 ml) at room temperature was added 1M diborane in THF (0.08 ml, 0.08 mmol). The mixture was stirred at room temperature for 3 hours, then an additional aliquot of 1M diborane in THF (0.16 ml, 0.16 mmol) was added. The mixture was stirred for 17 hours, then a premixed solution of aqueous 5M NaOH (20 μl, 0.100 mmol) and 30% aqueous hydrogen peroxide (10 μl, 11 mg, 0.100 mmol) was added. After 20 hours, the mixture was poured into saturated aqueous sodium thiosulfite (20 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resultant oil was chromatographed using a 12 g silica gel cartridge eluted with 0-100% ethyl acetate in hexanes over 20 column volumes. The desired product fractions were combined and concentrated under reduced pressure. The resulant oily film was dissolved in DCM (1.0 ml) and TFA (1.0 ml). The mixture was stirred for 17 hours, then concentrated under reduced pressure. The resultant film was chromatographed using a Gilson reverse phase prep HPLC eluted with 10-90% acetonitrile in water (with 0.05% TFA). The desired product fractions were combined, frozen at −78° C., and lyophilized to dryness to provide the title compound as a white solid. LC-MS: calculated for C23H24ClN3O7S 521.10 observed m/e: 522.28 (M+H)+ (Rt 1.58/2 min).

1. stirringThe mixture was stirred for 17 hours
2. waitAfter 20 hours
3. extractionextracted with ethyl acetate (2×50 ml)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resultant oil was chromatographed
7. washeluted with 0-100% ethyl acetate in hexanes over 20 column volumes
8. concentrationconcentrated under reduced pressure
9. dissolutionThe resulant oily film was dissolved in DCM (1.0 ml)
10. stirringThe mixture was stirred for 17 hours
11. concentrationconcentrated under reduced pressure
12. customThe resultant film was chromatographed
13. washeluted with 10-90% acetonitrile in water (with 0.05% TFA)
14. temperaturefrozen at −78° C.

ORDレコード

ord-901282639e66457baec31e7ac992c1a4

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09290517B2