(Dimethyl sulfide)trihydroboron → (1R)-1-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)ethanol

To a solution of (2R)-N-{(2R)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-hydroxyethyl}-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 355, 7.67 mmol, 1 eq.) in THF (150 mL) at room temperature was added slowly borane-methyl sulfide complex (2M in THF, 38.4 mmol, 5.0 eq.). After completion of the addition, the reaction mixture was heated to reflux for 2 hours and was then cooled to room temperature. The excess borane was quenched by the dropwise addition of EtOH (9 mL) followed by the slow addition of 2 M HCl (40 mL). The resulting mixture was heated to reflux for 1 hour and was then allow to cool to room temperature. The mixture was basified with 1N NaOH and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, using a gradient of 1:4 hexanes: EtOAc to 1:10 MeOH:EtOAc). The product was obtained as a pale yellow oil in 63% yield. MH+=503.9, RT=3.23 min.

1. additionAfter completion of the addition
2. temperaturethe reaction mixture was heated
3. temperatureto reflux for 2 hours
4. customThe excess borane was quenched by the dropwise addition of EtOH (9 mL)
5. additionfollowed by the slow addition of 2 M HCl (40 mL)
6. temperatureThe resulting mixture was heated
7. temperatureto reflux for 1 hour
8. temperatureto cool to room temperature
9. extractionextracted with ethyl acetate
10. extractionThe organic extract
11. washwas washed with brine
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated
14. custompurified by medium pressure column chromatography (Biotage 40S normal phase silica gel column
15. customThe product was obtained as a pale yellow oil in 63% yield

ORD record

ord-de556779dd3d470cb765f3bc8e224ce6

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06660752B2