Piperidine → HCID 61265491, compound

To a solution of (9H-fluoren-9-yl)methyl (2-isopropyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)carbamate (2.047 g, 5.23 mmol) in DMF (30 mL) was added piperidine (2.59 mL, 26.1 mmol) at room temperature. Upon completion of addition the reaction mixture was added to water (30 mL). The resulting suspension was diluted with water (100 mL) and extracted with EtOAc. The combined organics were extracted with 2M HCl (aq) and the acidic aqueous extracts were neutralised with a saturated sodium bicarbonate solution and loaded onto a C18 cartridge. The column was eluted with water and the collected aqueous was slurried with SCX-2 and filtered. The resin was rinsed with MeOH and 7M ammonia in MeOH. The MeOH and aqueous filtrate solvent was removed under reduced pressure. MeOH (150 mL) was added to the resulting mixture, sonicated, filtered and the filtrate was concentrated under reduced pressure. EtOH was added to the resulting mixture and it was filtered. The filtrate was concentrated under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography using a gradient of 0-10% MeOH in DCM afforded crude material. The crude material in MeOH was slurried with SCX-2 (30 g). The suspension was filtered and washed with MeOH. The resin was then eluted with 7M NH3 in MeOH. The methanolic ammonia was concentrated under reduced pressure to afford crude material. The crude material was then adsorbed onto silica and purification by chromatography using a gradient of 0-10% MeOH in DCM afforded the title compound;

1. additionUpon completion of addition the reaction mixture
2. extractionextracted with EtOAc
3. extractionThe combined organics were extracted with 2M HCl (aq)
4. washThe column was eluted with water
5. filtrationfiltered
6. washThe resin was rinsed with MeOH and 7M ammonia in MeOH
7. customThe MeOH and aqueous filtrate solvent was removed under reduced pressure
8. additionMeOH (150 mL) was added to the resulting mixture
9. customsonicated
10. filtrationfiltered
11. concentrationthe filtrate was concentrated under reduced pressure
12. additionEtOH was added to the resulting mixture and it
13. filtrationwas filtered
14. concentrationThe filtrate was concentrated under reduced pressure
15. customThe crude material was adsorbed onto silica and purification by chromatography
16. customafforded crude material
17. filtrationThe suspension was filtered
18. washwashed with MeOH
19. washThe resin was then eluted with 7M NH3 in MeOH
20. concentrationThe methanolic ammonia was concentrated under reduced pressure
21. customto afford crude material
22. customThe crude material was then adsorbed onto silica and purification by chromatography

ORD record

ord-c545320f06ff4093aa5e55331336054b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403810B2