(2,4-Dichlorophenyl)boronic acid → (+/-)-cis-6-(2,4-Dichlorophenyl)-1,2,3,4,7b,8,9,10,11,11a-decahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indole

Temperature

90 °C

tert-butyl (±)-cis-bromo-4-oxo-1,2,3,4,7b,10,11,11a-octahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indol-9(8H)-carboxylate from EXAMPLE 70, Part E (150 mg, 0.356 mmol), 2,4-dichlorophenylboronic acid (82 mg, 0.430 mmol) and barium hydroxide (170 mg, 0.540 mmol) were dissolved in DME (7 mL) and water (4 mL), and degassed for 10 minutes under nitrogen. Tetrakis (triphenylphosphine)palladium (O) (10 mg, 0.007 mmol) was added and the reaction was heated to 90° C. for 13 h. The reaction was cooled to room temperature and diluted with ethyl acetate (20 mL) and water (20 mL). The organic layer was separated and dried over magnesium sulfate, filtered and concentrated under reduced pressure to give an oil. The oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes). Fractions were collected, concentrated to a solid, then dissolved in 20% TFA/CHCl3 and stirred for 1 hour. The reaction solution was cooled to 0° C. in an ice bath, and basified to pH=10 with concentrated NH4OH. This was extracted with CHCl3 (3×15 ml), organics collected, dried over MgSO4 and concentrated under reduced pressure to give to give the title compound. 1H NMR(CDCl3, 300 MHz): δ 7.52 (d, 1H, J=1.8 Hz), 7.44 (d, 1H, J=1.8 Hz), 7.26-7.20 (m, 2H), 6.45 (s, 1H), 4.34 (t, 2H, J=9.2 Hz), 4.14-4.06 (m, 2H), 3.18-2.95 (m, 3H), 2.88-2.75 (m, 3H), 2.14 (s-br, 1H), 1.96-1.79 (m, 2H) ppm.

1. customwater (4 mL), and degassed for 10 minutes under nitrogen
2. temperatureThe reaction was cooled to room temperature
3. customThe organic layer was separated
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give an oil
8. customThe oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes)
9. customFractions were collected
10. concentrationconcentrated to a solid
11. dissolutiondissolved in 20% TFA/CHCl3
12. temperatureThe reaction solution was cooled to 0° C. in an ice bath
13. extractionThis was extracted with CHCl3 (3×15 ml), organics collected
14. dry with materialdried over MgSO4
15. concentrationconcentrated under reduced pressure
16. customto give

ORD record

ord-faaad5c73fea483c80174ebec5110e08

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06699852B2