Reaktion #70693

ord-b30f89a4910b430b8be344877c42da2a

Reaktionsgleichung

N#N
N2
CS(=O)[O-].[Na+]
sodium methanesulfinate
CN(C)CCN
N,N-dimethyletylene diamine
Cc1cc(C)c(CNC(=O)c2cc(Br)cc3c2c(C)cn3C2CC2)c(=O)[nH]1
6-bromo-1-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1H-indole-4-carboxamide
N
ammonia
Cc1cc(C)c(CNC(=O)c2cc(S(C)(=O)=O)cc3c2c(C)cn3C2CC2)c(=O)[nH]1
1-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-6-(methylsulfonyl)-1H-indole-4-carboxamide
Ausbeute 79.0%

Reaktionsbedingungen

Temperatur
120°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe deep blue reaction
  2. 2
    SonstigeThe vial was sealed
  3. 3
    ExtraktionThe mixture was extracted with 30% THF/EtOAc (2×) (
  4. 4
    Temperaturto warm
  5. 5
    TrocknenCombined organics, dried over magnesium sulfate
  6. 6
    Filtrationfiltered through Celite
  7. 7
    Einengenconcentrated
  8. 8
    SonstigePurification of the residue by column chromatography (12 gram Isco GOLD silica column

Vorschrift

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-dimethyletylene 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.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08536179B2uspto-grants-2013_09