Dimethylformamide → 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde

Temperature

0 °C

1.6 M n-Butyllithium in hexanes (1.6 mL, 2.6 mmol) was added dropwise to a solution of N,N-diisopropylamine (0.38 mL, 2.7 mmol) in THF (5.5 mL) at −78° C. Upon complete addition, the reaction temperature was raised to 0° C. for 30 minutes. After re-cooling to −78° C., 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine (0.50 g, 1.7 mmol, prepared as in Example 2, Step 1) in THF (2.5 mL) was added dropwise. After stirring for 1 hour at −78° C., N,N-dimethylformamide (0.26 mL, 3.4 mmol) was added. After 25 minutes, the reaction was quenched by the addition of saturated NH4Cl solution into the −78° C. mixture. After warming to room temperature, the mixture was diluted with water and extracted with EtOAc. The combined extracts were washed twice with water, once with brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-20% EtOAc in hexanes afforded product as a white solid (0.43 g, 78%).

1. additionUpon complete addition
2. temperatureAfter re-cooling to −78° C.
3. waitAfter 25 minutes
4. customthe reaction was quenched by the addition of saturated NH4Cl solution into the −78° C. mixture
5. temperatureAfter warming to room temperature
6. additionthe mixture was diluted with water
7. extractionextracted with EtOAc
8. washThe combined extracts were washed twice with water, once with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. washFlash chromatography, eluting with a gradient from 0-20% EtOAc in hexanes afforded product as a white solid (0.43 g, 78%)

ORD record

ord-2136f6ea13f641fdaca4e79afd71912c

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309246B2