Reacción #218108

Ecuación de reacción

ethyl acetate

6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

K2CO3

4-bromo-1,1,1-trifluorobutane

→

title compound

6-[2-(4,4,4-Trifluorobutyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy]nicotinamide

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat 50° C.
2. 2
   Otroovernight
3. 3
   LavadoWash with water (1×30 mL) and brine (1×30 mL)
4. 4
   SecadoDry the organic layer over Na2SO4
5. 5
   Filtraciónfilter
6. 6
   Concentraciónconcentrate
7. 7
   OtroPurify by flash chromatography
8. 8
   Lavadoeluting with 6% to 20% (2.0 M NH3 in methanol) in ethyl acetate

Procedimiento

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 0.350 g, 1.24 mmol), K2CO3 (0.427 g, 3.09 mmol), and 4-bromo-1,1,1-trifluorobutane (0.248 g, 1.30 mmol) in DMF (6.2 mL). Beat at 95° C. for 5.5 hours, then at 50° C. overnight. Cool the reaction mixture to room temperature and add ethyl acetate (100 mL). Wash with water (1×30 mL) and brine (1×30 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 6% to 20% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound: MS ES+394.2 (M+H)+, HRMS calcd for C20H23N3O2F3 394.1742 (M+H)+, found 394.1733, time 0.53 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=10.1 min, 100% purity.

Fuente