Dimethylformamide → 1-(Phenylsulfonyl)-1H-pyrrolo(2,3-b)pyridine-2-carboxaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (4.13 mL, 0.029 mol) in anhydrous tetrahydrofuran (THF) (50 mL) stirred under nitrogen at −78° C. was added nBuLi (10.42 mL, 0.026 mol) over 15 min. The reaction mixture was stirred at −78° C. for 30 min. then warmed to r.t. and stirred for 1 h. To this solution of LDA in anhydrous tetrahydrofuran (THF) (250 mL) stirred under nitrogen at −30° C. was added a solution of 1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (5 g, 19.36 mmol) and TMEDA (4.38 mL, 29.0 mmol) in tetrahydrofuran (THF) (150 mL) dropwise over 15 min. The reaction mixture was stirred at −30° C. for 2.5 h, then DMF (3 mL, 38.7 mmol) was added dropwise over 1 min. The reaction mixture was stirred at −30° C. for another 2 h, TLC and LC-MS showed complete conversion. The reaction mixture was quenched with water and partitioned between dichloromethane (700 mL) and water (100 mL). The organic phase was washed with water (3×100 mL), dried over sodium sulfate and evaporated in vacuo to give the crude product as a yellow solid. This was purified by recrystallization (EtOAc and PE) to give the desired product—1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (4.8 g, 78%) as a yellow solid.

1. temperaturethen warmed to r.t.
2. stirringstirred for 1 h
3. stirringThe reaction mixture was stirred at −30° C. for 2.5 h
4. stirringThe reaction mixture was stirred at −30° C. for another 2 h
5. customThe reaction mixture was quenched with water
6. custompartitioned between dichloromethane (700 mL) and water (100 mL)
7. washThe organic phase was washed with water (3×100 mL)
8. dry with materialdried over sodium sulfate
9. customevaporated in vacuo
10. customto give the crude product as a yellow solid
11. customThis was purified by recrystallization (EtOAc and PE)

ORD record

ord-fdda8e762bf14ef8b40ddbea9da970e6

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09127003B2