Hydrochloric Acid → (3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-yl)amine

Temperature

0 °C

Hydrochloric acid (in dioxane, 4M, 50 ml) was added into a solution of the product of Step 5 (5.71 g, 12 mmol) in methanol (100 ml) at 0° C. The solution was stirred at 0° C. for 1 hr and then at ambient temperature for a further 1 hr. The reaction mixture was concentrated in vacuo, diluted with saturated sodium hydrogen carbonate and extracted with ethyl acetate (3×100 ml). The organic extract were washed with brine, dried over MgSO4 and concentrated in vacuo, then eluted through an SCX cartridge (50 g) with methanol (100 ml) and then with ammonia in methanol (2M, 50 ml). The fraction containing the product was concentrated in vacuo, to afford (3-chloro-4-{(E)-2-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-yl]vinyl}bicyclo[4.2.1]non-3-en-9-yl)amine (3.76 g, 84%). δH (400 MHz, CDCl3) 1.33-1.61 (4H, m), 1.74-1.92 (2H, m), 2.15-2.23 (1H, br), 2.30-2.39 (1H, br), 2.54-2.69 (3H, m), 3.12 (1H, d, J 18.0), 3.34 (1H, t, J 6.5), 3.82 (3H, s), 6.47 (1H, s), 6.65 (1H, d, J 16.5), 7.15 (2H, t, J 8.5), 7.37-7.41 (2H, m), 7.47 (1H, d, J 16.5)

1. waitat ambient temperature for a further 1 hr
2. concentrationThe reaction mixture was concentrated in vacuo
3. additiondiluted with saturated sodium hydrogen carbonate
4. extractionextracted with ethyl acetate (3×100 ml)
5. extractionThe organic extract
6. washwere washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. washeluted through an SCX cartridge (50 g) with methanol (100 ml)
10. additionThe fraction containing the product
11. concentrationwas concentrated in vacuo

ORD record

ord-b927d7787b0a4f17b6e6a888a472b718

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452899B2