Reaktion #964536

ord-9bc49c3e909644918539c59a87a8e2e9

Lösungsmittel

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe solvents were removed by concentration
  2. 2
    workup.STIRRINGstirred at room temperature for 0.5 h
  3. 3
    SonstigeThe solvent was removed
  4. 4
    Sonstigethe residue was purified by silica gel flash chromatography (30-100% EtOAc in Hex)

Vorschrift

To a solution of 2-methyl-N-[(S)-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]{1-[(trimethylsilyl)methyl]-1H-1,2,3-triazol-4-yl}methyl]propane-2-sulfinamide (1.3 g, 2.8 mmol) in MeOH (6.3 mL) was added a solution of HCl in ether (6.3 mL, 2 M). The reaction was stirred at room temperature for 1 h. The solvents were removed by concentration. The resulted amine bis-HCl salt (0.3 g, 0.69 mmol) was mixed with 4-isopropylpheylacetic acid (0.12 g, 0.69 mmol), HOAt (0.094 g, 0.69 mmol), EDC (0.13 g, 0.69 mmol) and diisopropylethyl amine (0.23 mL, 1.4 mmol) in CH2Cl2 (3.5 mL) and stirred at room temperature for 0.5 h. The solvent was removed and the residue was purified by silica gel flash chromatography (30-100% EtOAc in Hex) to give the amide product. To a solution of this amide (0.23 g, 0.45 mmol) in THF (3 mL) was added a solution of TBAF (0.5 mL, 1M in THF). The reaction mixture was stirred at rt for 1 h. The solvent was removed and the residue was purified by silica gel flash chromatography (50-100% EtOAc in hex) to provide 2-(4-isopropylphenyl)-N-{(S)-1-methyl-1H-1,2,3-triazol-4-yl)[4-(2,2,2-trifluoroethoxy)-phenyl]methyl}acetamide (0.12 g, 59%). 1H NMR (CDCl3, 400 MHz) δ 8.22 (d, J=2.8 Hz, 1H), 7.40 (s, 1H), 7.39 (d, J=7.2 Hz, 1H), 7.33 (d, J=8.8 Hz, 1H), 7.24-7.19 (m, 5H), 6.27 (d, J=6.8 Hz, 1H), 4.31 (dd, J=7.6, 8.4 Hz, 2H), 4.00 (s, 3H), 3.62 (s, 2H), 2.90 (m, J=6.8 Hz, 1H), 1.25 (d, J=6.8 Hz, 6H). HRMS (ES) [M+1]+ calcd for C22H24F3N5O2: 448.1955, Found: 448.1956.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08987310B2uspto-grants-2015_03