Reaktion #1865177

ord-d06b10aeb21645c894b02c828fecf51b

Lösungsmittel

Reaktionsbedingungen

Temperatur
0°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturto warm to room temperature
  2. 2
    workup.STIRRINGthe reaction mixture was stirred at room temperature overnight
  3. 3
    SonstigeThe reaction mixture was quenched with MeOH (100 mL) and solid
  4. 4
    Sonstigeprecipitates
  5. 5
    Filtrationwere filtered off
  6. 6
    EinengenSolvents were concentrated
  7. 7
    Sonstigethe crude material was purified by silica gel column chromatography
  8. 8
    Wascheneluting with a gradient of MeOH (0-4%) in DCM
  9. 9
    Sonstigefollowed by re-purification with a gradient of EtOAc (0-40%) in heptane
  10. 10
    workup.ADDITIONFractions containing the product

Vorschrift

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 524 mg, 2.73 mmol) in DMF (1.5 mL) was added drop wise to a cooled suspension of di(1H-1,2,4-triazol-1-yl)methanone (448 mg, 2.73 mmol) in DMF (1.5 mL) at 0° C. The reaction mixture was stirred for 3 h at 0° C., after which it was allowed to warm to room temperature. A solution of (racemic) 6-(1-((tert-butyldimethylsilyl)oxy)ethyl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 185, 500 mg, 1.364 mmol) in DMF (2.0 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (100 mL) and solid precipitates were filtered off. Solvents were concentrated and the crude material was purified by silica gel column chromatography eluting with a gradient of MeOH (0-4%) in DCM, followed by re-purification with a gradient of EtOAc (0-40%) in heptane. Fractions containing the product were combined to yield the title compound as a waxy solid. (UPLC-MS 3) tR 1.66 min, ESI-MS 585.3 [M+H]+.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09266883B2uspto-grants-2016_02