Reacción #967215

Ecuación de reacción

solution

N-(cis-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide

boron trichloride-methyl sulfide complex

→

Solvent B

tetrahydropyridinedione

Solvent A

Pyrrolidinone

Disolventes

DCM

DCE

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction mixture was quenched with ice and MeOH and example 8

Procedimiento

To a solution of Example 8A (13 mg, 0.028 mmol) in DCM (0.5 mL) and DCE (0.5 mL) was added boron trichloride-methyl sulfide complex (30.6 mg, 0.171 mmol). The reaction mixture was stirred at 70° C. for 16 h. The reaction mixture was quenched with ice and MeOH and example 8 isolated via prep HPLC (10 minute gradient from 5 to 100% B; Column: Phenomenex AXIA Luna 100×20 mm 5 μm; Solvent A: 10% ACN-90% H2O-0.1% TFA; Solvent B: 90% ACN-10% H2O-0.1% TFA). The desired fractions were evaporated to dryness to give Example 8 (5 mg, 0.01 mmol, 40% yield). LCMS RT=2.27 min, [M+1]=443.1 {(MeOH/H2O/TFA) Phenom. Luna C18; 50×4.6 mm; 4 min Grad}; HPLC (150×4.6 mm 3.5 μm, 254 nm): Sunfire {RT=11.2 min, 95%}; Xbridge {RT=9.9 min, 96.3%}. 1H NMR (500 MHz, MeOD) δ ppm 2.01-2.06 (m, 3H) 2.19-2.25 (m, 1H) 3.59 (s, 3H) 4.20 (t, J=6.33 Hz, 1H) 5.33 (t, J=5.64 Hz, 1H) 6.74 (d, J=7.43 Hz, 1H) 6.86 (d, J=7.70 Hz, 1H) 7.10 (dd, J=8.25, 1.93 Hz, 1H) 7.14 (d, J=7.43 Hz, 1H) 7.18 (t, J=7.57 Hz, 1H) 7.24 (t, J=7.29 Hz, 1H) 7.34 (d, J=2.20 Hz, 1H) 7.39 (d, J=7.43 Hz, 1H) 7.43-7.46 (m, 1H).

Fuente