Boron tribromide → HCID 24782920, 화합물

1-{[3-(4-{[(2R)-4-[5-Fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)phenyl]carbonyl}-D-prolinamide (340 mg, 0.5185 mmol) was dissolved in anhydrous dichloromethane (12 mL) and cooled to −78° C. (cardice/acetone bath) under nitrogen. Boron tribromide (1.0M in dichloromethane, 2.57 mL, 2.57 mmol) was then added portionwise and after 5 minutes the stirred mixture was allowed to warm slowly to room temperature under nitrogen. After 4 hours, LCMS suggested little reaction had occurred and the mixture was re-cooled to −78° C. and additional boron tribromide (1.0M in dichloromethane, 2 mL, 2 mmol) was added and the mixture was then stirred at room temperature overnight. LCMS still indicated the reaction was incomplete and the mixture was re-cooled to −78° C. once more and more boron tribromide (1.0M in dichloromethane, 2 mL, 2 mmol) was added and the mixture stirred at room temperature for 3 hours before being re-cooled to −78° C. and quenched by the gradual addition of methanol (5 mL). The reaction was warmed to room temperature when more dichloromethane (30 mL) and aqueous saturated sodium hydrogen carbonate solution (75 mL) were added and the mixture stirred vigorously for 5 minutes. The organic phase was separated by passing through a hydrophobic frit and evaporated in vacuo. This crude product was purified by mass-directed autopreparation. Product containing fractions were combined and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was washed successively water and brine, dried through a hydrophobic frit and evaporated in vacuo to give the title compound (98 mg).

1. customreaction
2. temperaturethe mixture was re-cooled to −78° C.
3. temperaturethe mixture was re-cooled to −78° C. once more
4. stirringthe mixture stirred at room temperature for 3 hours
5. temperaturebefore being re-cooled to −78° C.
6. customquenched by the gradual addition of methanol (5 mL)
7. temperatureThe reaction was warmed to room temperature when more dichloromethane (30 mL) and aqueous saturated sodium hydrogen carbonate solution (75 mL)
8. additionwere added
9. stirringthe mixture stirred vigorously for 5 minutes
10. customThe organic phase was separated
11. customevaporated in vacuo
12. customThis crude product was purified by mass-directed autopreparation
13. additionProduct containing fractions
14. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
15. washThe organic layer was washed successively water and brine
16. customdried through a hydrophobic frit
17. customevaporated in vacuo

ORD 기록

ord-7b36cc6cc88d43bf96ce19e5782a1787

출처 데이터셋

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07943651B2