Reacción #331333

Ecuación de reacción

EDC

HOBT

C-(3-Chloro-pyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine

3-Methylenecyclobutanecarboxylic acid

→

desired product

3-Methylenecyclobutanecarboxylic acid [(3-chloropyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]-amide

Disolventes

CH2Cl2

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONadded to the homogenous reaction mixture
2. 2
   ConcentraciónAfter 24 h the reaction was concentrated in vacuo
3. 3
   workup.DISSOLUTIONdissolved in EtOAc
4. 4
   Lavadothe organic layer was washed with sat. NaHCO3
5. 5
   LavadoThe organic layer was washed with H2O and brine
6. 6
   Secadodried over sodium sulfate
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   OtroThe crude product was purified by silica gel column chromatography [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc:Hex]

Procedimiento

C-(3-Chloro-pyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine (690 mg, 1.99 mmol) was dissolved in 6.0 mL of CH2Cl2 followed by the addition of EDC (600 mg, 2.98 mmol) and HOBT (300 mg, 1.99 mmol). 3-Methylenecyclobutanecarboxylic acid (300 mg, 2.59 mmol) was dissolved in 1.0 mL of CH2Cl2 and added to the homogenous reaction mixture. After 24 h the reaction was concentrated in vacuo and dissolved in EtOAc and the organic layer was washed with sat. NaHCO3. The organic layer was washed with H2O and brine. The organic layers where combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc:Hex] to obtain the desired product as a white fluffy solid; 1H NMR (400 MHz, CDCl3): δ=2.82-2.92 (m, 2H), 2.99-3.06 (m, 2H), 4.77-4.80 (m, 2H), 6.81 (d, 1H, J=7.8 Hz), 7.45-7.54 (m, 3H), 7.83-7.88 (m, 3H), 8.10 (d, 2H, J=7.1 Hz), 8.22-8.23 (brm, 1H), 8.39 (d, 1H, J=1.79 Hz), 8.59 (d, 1H, J=2.5 Hz); MS (ES+): 440.93 (M+1), 442.91 (M+3).

Fuente