Methanol → 1H-Pyrrolo[2,3-b]pyridine-5-methanamine, 2-(trifluoromethyl)-

2-(Trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (Intermediate 4, 1.48 g, 7.01 mmol) was dissolved in THF (59 mL), cooled in an ice bath and treated with a 1M solution of borane tetrahydrofuran complex (35.0 mL, 35.0 mmol) dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 18 hours. Methanol (59 mL) was added dropwise and the reaction mixture was stirred for 20 minutes at room temperature. The solvent was removed under reduced pressure and the residue was dissolved in methanol (177 mL) and heated under reflux for 4 hours. The reaction mixture was allowed to cool to room temperature and passed down an SCX column (20 g) eluting with methanol, followed by 2M ammonia/methanol. Basic fractions were combined and evaporated under reduced pressure. The residue was purified by column chromatography eluting with a gradient of 0-10% 2M ammonia/methanol and DCM. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow solid (1.1 g);

1. temperaturecooled in an ice bath
2. stirringthe reaction mixture was stirred for 20 minutes at room temperature
3. customThe solvent was removed under reduced pressure
4. dissolutionthe residue was dissolved in methanol (177 mL)
5. temperatureheated
6. temperatureunder reflux for 4 hours
7. temperatureto cool to room temperature
8. washeluting with methanol
9. customevaporated under reduced pressure
10. customThe residue was purified by column chromatography
11. washeluting with a gradient of 0-10% 2M ammonia/methanol and DCM
12. additionProduct containing fractions
13. customevaporated under reduced pressure

ORD record

ord-6cea8dfd4f9245aa86ee5362a80f07a9

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796283B2