Reacción #51538

Ecuación de reacción

tert-butyl (7bR,11aS)-6-bromo-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate

2-methyl 4 methoxyphenyl boronic acid

→

title compound

Rendimiento 45.0%

(7bR,11aS)6-(4-methoxy-2-methylphenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole

Rendimiento 45.0%

Disolventes

ethyl acetate

DME

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe mixture was degassed with a stream of nitrogen for 20 min
2. 2
   Temperaturato cool to ambient temperature
3. 3
   Lavadowashed with sat'd aqueous sodium bicarbonate and brine
4. 4
   Secadodried (MgSO4)
5. 5
   Filtraciónfiltered through Celite
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   OtroThe residue was purified by flash chromatography (elution with hexanes/ethyl acetate)

Procedimiento

To a solution of tert-butyl (7bR,11aS)-6-bromo-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 7, Part A (80 mg, 0.18 mmol) in 25 mL of DME (10 mL) was added 2-methyl 4 methoxyphenyl boronic acid (45 mg, 0.27 mmol) and TEA (0.26 mL, 1.8 mmol). The mixture was degassed with a stream of nitrogen for 20 min and then there was added Pd(dppf)2 (15 mg, 0.1 mmol) and the mixture was stirred at 85° C. for 16 h. The reaction was allowed to cool to ambient temperature and was diluted with ethyl acetate, washed with sat'd aqueous sodium bicarbonate and brine, dried (MgSO4), filtered through Celite and concentrated in vacuo. The residue was purified by flash chromatography (elution with hexanes/ethyl acetate) to afford (35 mg, 45% yield) of the title compound. 1H NMR (CDCl3, 300 MHz): δ 7.13 (d, 1H, J=8.1 Hz), 6.97 (s, 1H), 6.75 (m, 3H), 3.83 (s, 3H), 3.79 (m, 1H), 3.65 (m, 2H), 3.52 (m, 3H), 3.21 (m, 2H), 3.01 (m, 2H), 2.24 (s, 3H), 1.97 (m, 2H), 1.60)m, 2H), 1.21 (s, 9H). LRMS (ES+): 467 (M+H)+.

Fuente