Nitrogen → HCID 69894712, compound

Temperature

80 °C

A 30-mL shaker vial was charged with di(tert-butyl) 10-bromo-1,2,4,5,5a,10b-hexahydroazepino[4,5-b]indole-3,6-dicarboxylate (0.10 g, 0.214 mmol), potassium phosphate (0.068 g, 0.32 mmol), benzo[b]furan-2-boronic acid (0.104 g, 0.642 mmol), and DMF (2 mL). The vial was purged with N2, and tetrakis(triphenylphosphine)palladium (0.025 g, 0.02 mmol) was added and the mixture was agitated at 250 RPM with heating at 80° C. overnight. The mixture was filtered through Celite, washing with MeOH (3-5 mL), and sulfonic acid resin (DOWEX®50W-X2, washed and dried, 4.8 meq/g dry weight) was added (1 g). The vial was then purged with N2, capped and agitated at 250 RPM with heating at 65° C. for 36 h. The mixture was filtered through a scintered funnel and the resin was washed 1:1 methylene chloride/methanol and then consecutively washed with MeOH and THF to ensure that all excess reagent was removed from the resin (the methanol and THF washes are alternated to swell and then shrink the resin to help expel reagents from inside the resin). The resin was then washed with 4M ammonium hydroxide in methanol (4×2 ml) and THF (2×2 ml) into an accurately weight round-bottomed flask. The filtrate was concentrated to give 0.042 g (65%) of a beige solid, which was dissolved in methylene chloride and crystallized to give 0.020 g of the title compound as beige solid: MS (EI) m/z 304 (M+), 302, 260, 259, 258, 247, 246, 207, 195, 153; 1H NMR (CDCl3) δ 7.64 (d, J=7 Hz, 1 H), 7.53 (d, J=8 Hz, 1 H), 7.35-7.22 (m, 3 H), 7.15 (t, J=8 Hz, 1 H), 6.63 (d, J=8 Hz, 1 H), 4.38-4.27 (m, 1H), 4.16-4.06 (m, 1 H), 3.28-3.22 (m, 1 H), 3.17-3.11 (m, 1 H), 2.95-2.79 (m, 2 H), 2.38-2.26 (m, 1 H), 2.10-1.89 (m, 2 H), 1.81-1.72 (m, 1 H) ppm.

1. additionwas added
2. filtrationThe mixture was filtered through Celite
3. washwashing with MeOH (3-5 mL), and sulfonic acid resin (DOWEX®50W-X2, washed and dried, 4.8 meq/g dry weight)
4. additionwas added (1 g)
5. customThe vial was then purged with N2
6. customcapped
7. stirringagitated at 250 RPM
8. temperaturewith heating at 65° C. for 36 h
9. filtrationThe mixture was filtered through a scintered funnel
10. washthe resin was washed 1:1 methylene chloride/methanol
11. washconsecutively washed with MeOH and THF
12. customwas removed from the resin (the methanol and THF washes
13. washThe resin was then washed with 4M ammonium hydroxide in methanol (4×2 ml) and THF (2×2 ml) into an accurately weight round-bottomed flask
14. concentrationThe filtrate was concentrated

ORD record

ord-7f26652a98ff4137a863e8181082197a

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06828314B2