反应详情

1-(8-Bromo-quinolin-2-yl)-6,7-dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalene 81C (700 mg, 1.83 mMol) and piperidin-4-yl-carbamic acid tert-butyl ester (733 mg, 3.66 mMol) were dissolved in 6.0 mL of dioxane under an atmosphere of dry N2. To this solution was added Cs2CO3 (835 mg, 2.56 mMol), racemic-BINAP (68 mg, 0.109 mMol) and tris(dibenzylideneacetone)dipalladium (0) (34 mg, 0.037 mMol) and the reaction mixture was heated to reflux and reacted at this temperature overnight. The mixture was then cooled to ambient temperature, filtered; and concentrated under vacuum to give 1.12 g of an orange film. The film was dissolved in a solution of 5 mL of TFA and 5 mL of DCM under an atmosphere of dry N2. The reaction mixture was stirred at ambient temperature for 30 minutes after which time it was concentrated under vacuum to give a yellow oil. The oil was partitioned between ethyl ether and 0.1 N aqueous HCl. The aqueous layer was then washed with DCM. The aqueous layer was basified to pH˜11 with NaOH. The resulting solution was washed three times with DCM. The DCM extracts were combined, dried over Na2SO4, filtered and concentrated to give 500 mg of a yellow solid. The solid was chromatographed on flash silica gel eluting with MeOH/DCM (1090) to give 127 mg of the title compound 81 as a yellow solid.

1. temperatureto reflux
2. customreacted at this temperature overnight
3. filtrationfiltered
4. concentrationand concentrated under vacuum
5. customto give 1.12 g of an orange film
6. concentrationwas concentrated under vacuum
7. customto give a yellow oil
8. customThe oil was partitioned between ethyl ether and 0.1 N aqueous HCl
9. washThe aqueous layer was then washed with DCM
10. washThe resulting solution was washed three times with DCM
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated