Reacción #90591

ord-c057605e474f4e24b1c64891e09632fa

Condiciones de reacción

Temperatura
120°CELSIUS
Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    OtroThe deep blue reaction
  2. 2
    OtroThe vial was sealed
  3. 3
    ExtracciónThe mixture was extracted with 30% THF/EtOAc (2×) (
  4. 4
    Temperaturato warm
  5. 5
    SecadoCombined organics, dried over magnesium sulfate
  6. 6
    Filtraciónfiltered through Celite
  7. 7
    Concentraciónconcentrated
  8. 8
    OtroPurification of the residue by column chromatography (12 gram Isco GOLD silica column

Procedimiento

To a vial under a stream of N2 was added copper(II) trifluoromethanesulfonate (0.084 g, 0.233 mmol), sodium methanesulfinate (0.056 g, 0.467 mmol), DMSO (1.3 mL), and N,N-dimethylethylene diamine (0.053 mL, 0.490 mmol). The deep blue reaction was stirred for 5 min, then was added 6-bromo-1-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1H-indole-4-carboxamide (0.10 g, 0.233 mmol). The vial was sealed and heated at 120° C. for 3 h, at which time it was diluted with water (50 ml). The mixture was extracted with 30% THF/EtOAc (2×) (needed to warm to break up emulsion). Combined organics, dried over magnesium sulfate, filtered through Celite, and concentrated. Purification of the residue by column chromatography (12 gram Isco GOLD silica column; gradient B: 5-85%; A: dichloromethane, B: 10% (2 M ammonia in MeOH) in chloroform) provided 1-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-6-(methylsulfonyl)-1H-indole-4-carboxamide (83 mg, 0.184 mmol, 79% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50 (s, 1H), 8.38 (t, J=5.1 Hz, 1H), 8.06 (d, J=1.8 Hz, 1H), 7.46 (dd, J=7.8, 1.3 Hz, 2H), 5.87 (s, 1H), 4.34 (d, J=5.1 Hz, 2H), 3.52 (tt, J=7.0, 3.6 Hz, 1H), 3.20 (s, 3H), 2.23 (s, 3H), 2.11 (s, 3H), 2.14 (s, 3H), 1.09 (m, 2H), 0.96 (m, 2H). MS(ES) [M+H]+ 427.8.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US09446041B2uspto-grants-2016_09