Pyridine → HCID 9818490, compound

To a solution of 1-propanesulfonyl chloride (20.5 mg, 0.14 mmol) in dichloromethane (250 mL) was added pyridine (78 mL, 0.96 mmol) followed 5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenamine (30 mg, 0.096 mmol) dissolved in CH2Cl2 (1 mL). The CH2Cl2 was removed under vacuum and the reaction gently shaken at ambient temperature overnight. To the reaction was added 1.0 mL of CH2Cl2 followed by 200 mg of polymer supported trisamine (Argonaut laboratories). The reaction was shaken at room temperature for 30 minutes, the filtrate collected and the volume brought to 5 mL with dichloromethane. The organic layer was extracted with 10% aqueous citric acid (3×4 mL), brine (2×4 mL), filtered (Varian CE1000M)® and the solvent removed under vacuum. The resulting oil was dissolved in 2 mL of acetonitrile and 0.5 g of Amberlyst resin was added. The reaction was shaken at room temperature for 72 hours and filtered. The resin was washed with acetonitrile (2×2 mL), methanol (2×2 mL), and suspended in 2 M methanolic ammonia (2 mL) for 2 hours. The resin was filtered, washed with 0.5 mL of methanol and then retreated with ammonia as described. The ammonia and methanol filtrates were combined and the solvent removed under vacuum. The crude material was purified using reverse phase preparative HPLC. (6.7 mg, 21.9% yield).

1. customThe CH2Cl2 was removed under vacuum
2. customthe reaction
3. stirringThe reaction was shaken at room temperature for 30 minutes
4. customthe filtrate collected
5. extractionThe organic layer was extracted with 10% aqueous citric acid (3×4 mL), brine (2×4 mL)
6. filtrationfiltered (Varian CE1000M)®
7. customthe solvent removed under vacuum
8. dissolutionThe resulting oil was dissolved in 2 mL of acetonitrile
9. addition0.5 g of Amberlyst resin was added
10. stirringThe reaction was shaken at room temperature for 72 hours
11. filtrationfiltered
12. washThe resin was washed with acetonitrile (2×2 mL), methanol (2×2 mL)
13. waitsuspended in 2 M methanolic ammonia (2 mL) for 2 hours
14. filtrationThe resin was filtered
15. washwashed with 0.5 mL of methanol
16. customthe solvent removed under vacuum
17. customThe crude material was purified

ORD record

ord-717bc7e86f47420186fdf8478baca69e

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06503935B1