Reaktion #51547

Reaktionsgleichung

tert-butyl (±)Cis-bromo-4-oxo-1,2,3,4,7b, 10,11,11 a-octahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indol-9(8H)-carboxylate

(±)-cis-6-(2,6-difluorophenyl)-1,2,3,4,7b,8,9,10,11,11a-decahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indole

2,4-dichlorophenylboronic acid

barium hydroxide

→

title compound

(±)-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

Lösungsmittel

ethyl acetate

water

DME

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewater (4 mL), and degassed for 10 minutes under nitrogen
2. 2
   TemperaturThe reaction was cooled to room temperature
3. 3
   SonstigeThe organic layer was separated
4. 4
   Trocknendried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   Sonstigeto give an oil
8. 8
   SonstigeThe oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes)
9. 9
   SonstigeFractions were collected
10. 10
    Einengenconcentrated to a solid
11. 11
    workup.DISSOLUTIONdissolved in 20% TFA/CHCl3
12. 12
    TemperaturThe reaction solution was cooled to 0° C. in an ice bath
13. 13
    ExtraktionThis was extracted with CHCl3 (3×15 ml), organics collected
14. 14
    Trocknendried over MgSO4
15. 15
    Einengenconcentrated under reduced pressure
16. 16
    Sonstigeto give

Vorschrift

tert-butyl (±)Cis-bromo-4-oxo-1,2,3,4,7b, 10,11,11 a-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 (0) (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.

Quelle