Lithium Hexamethyldisilazide → 9-Benzenesulfonyl-5-hydroxy-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Temperature

-30 °C

Lithium bis(trimethylsilyl)amide (9.6 mL, 1N solution in THF, 9.60 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-2-{[cyanomethyl(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (1.72 g, 3.19 mmol) in dry THF (50 mL). The reaction mixture was allowed to warm to −30° C., stirred at −30° C. for 2 h, before warming to ambient temperature. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (50 mL). The aqueous phase was extracted with DCM (2×20 mL) and the combined organic phase was washed with brine and concentrated in vacuo. The resultant solid was triturated with THF (2×4 mL) to afford the title compound. The filtrate was purified by flash chromatography (silica, 5 g column, Si-SPE, ethyl acetate then 10-20% MeOH in DCM) to afford the remaining title compound. The two batches of material were combined to afford a yellow solid (1.03 g, 90%). LCMS (Method B): RT=3.26 min, M+H+=351.

1. temperaturea cooled
2. temperaturebefore warming to ambient temperature
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (50 mL)
4. extractionThe aqueous phase was extracted with DCM (2×20 mL)
5. washthe combined organic phase was washed with brine
6. concentrationconcentrated in vacuo
7. customThe resultant solid was triturated with THF (2×4 mL)

ORD record

ord-6a57ade0512f43538bc310d0a7584004

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501765B2