2-Amino-5-bromopyridine → alpha-(6-Amino-3-pyridinyl)-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo(2,3-b)pyridine-3-methanol

To 2-amino-5-bromopyridine (15, 3.10 g, 17.9 mmol) in tetrahydrofuran (80.0 mL) under an atmosphere of nitrogen at −78° C., a solution n-butyllithium (2.50 M in hexane, 7.10 mL) was added slowly. After 30 minutes, 1,2-bis-(chloro-dimethyl-silanyl)-ethane (3.90 g dissolved in tetrahydrofuran 20.0 mL, 18.1 mmol) was added to the reaction mixture slowly, and then allowed to warm to room temperature for 1 hour. The reaction was cooled to −78° C. followed by adding a solution of n-butyllithium (2.50 M in Hexane, 7.10 mL). The reaction mixture was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature for 60 minutes. The reaction mixture was cooled to −78° C., followed by adding a solution of n-butyllithium (2.50 M in Hexane, 7.50 mL) slowly. After 60 minutes, 1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (597, 1.90 g in 30 mL tetrahydrofuran, 5.92 mmol) was added to the reaction mixture. The reaction mixture was stirred at −78° C. for 2 hours, then allowed to warm to room temperature for 1 hour. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 2% to 20% methanol in dichloromethane to give the desired compound (598, 1.25 g, 50.9%). MS (ESI) [M+H+]+=415.2.

1. temperatureThe reaction was cooled to −78° C.
2. temperatureto warm to room temperature for 60 minutes
3. temperatureThe reaction mixture was cooled to −78° C.
4. waitAfter 60 minutes
5. stirringThe reaction mixture was stirred at −78° C. for 2 hours
6. temperatureto warm to room temperature for 1 hour
7. extractionextracted with ethyl acetate
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated
11. custompurified by silica gel column chromatography
12. washeluting with 2% to 20% methanol in dichloromethane

ORD-Eintrag

ord-a5b3c284dbd64f61bdaf726e5e13c817

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08461169B2