1-Pyrrolidineethanamine → HCID 89855301, compound

To a stirred suspension of 6-chloro-2-hydroxy-quinoline-4-carboxylic acid (preparation 8) (8.50 g, 38 mmol) in anhydrous DCM (250 ml), was added anhydrous DMF (2 ml) and thionyl chloride (11 ml, 152 mmol) at room temperature under argon. The mixture was refluxed for 3 h and then allowed to cool to room temperature. The solvents were removed under reduced pressure and the residue was dissolved in anhydrous THF (300 ml) under argon. 2-Pyrrolidin-1-ylethanamine (14 ml, 114 mmol) was added and the reaction was stirred at room temperature for 16 h. Solvents were removed under vacuum and the residue partitioned between NaHCO3 saturated aqueous solution (250 ml) and DCM (2×250 ml). The organic layers were combined, dried over MgSO4, filtrated and evaporated under reduced pressure. The crude was purified by column chromatography using a 120 g silica gel cartridge. Solvent A: DCM, Solvent B: 10% MeOH—NH3 in DCM. Gradient: 2 min hold 100% A followed by 18 min ramp to 30% B and then 15 min hold at 30% B. The relevant fractions were combined and concentrated to dryness under reduced pressure to obtain the desired product as an off-white solid (5.6 g, 16.6 mmol, 43%).

1. temperatureThe mixture was refluxed for 3 h
2. customThe solvents were removed under reduced pressure
3. dissolutionthe residue was dissolved in anhydrous THF (300 ml) under argon
4. customSolvents were removed under vacuum
5. customthe residue partitioned between NaHCO3 saturated aqueous solution (250 ml) and DCM (2×250 ml)
6. dry with materialdried over MgSO4
7. filtrationfiltrated
8. customevaporated under reduced pressure
9. customThe crude was purified by column chromatography
10. custom2 min
11. waitfollowed by 18 min ramp to 30% B
12. custom15 min
13. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-1fbb8a08bdee4513a7a66191ffb7ac11

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115088B2