Reacción #47267

ord-26411151e6a145f6abd6990de06e794a

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Lavadowashed with 2N aqueous hydrochloric acid, saturated sodium chloride solution
  2. 2
    Otrodried
  3. 3
    ConcentraciónThe organic layer was concentrated
  4. 4
    Otrothe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g silica gel; 0% to 10% methanol/dichloromethane)
  5. 5
    Otroto afford

Procedimiento

A solution of (S)-3-cyclohexyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (138 mg, 0.52 mmol), 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 98 mg, 0.63 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (326 mg, 0.75 mmol), N,N-diisopropylethylamine (200 mg, 1.54 mmol) in dichloromethane (10 mL) was stirred for 18 h under nitrogen at 23° C. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium chloride solution and dried. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g silica gel; 0% to 10% methanol/dichloromethane) to afford, (S)-3-cyclopentyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (123 mg, 59%) as a white foam, LR-ES-MS m/z calculated for C21H32N4O4 [M]+ 404, observed [M+H]+ 405; 1H NMR (300 MHz, CDCl3) δ ppm 0.78-1.31 (m, 7H) 1.15 (s, 6H) 1.55-1.77 (m, 5H) 1.77-1.95 (m, 2H) 3.82 (s, 3H) 3.87 (d, J=17.8 Hz, 1H) 3.94 (s, 2H) 4.05 (d, J=17.8 Hz, 1H) 4.92 (dd, J=9.5, 5.9 Hz, 1H) 5.14 (s, 1H) 6.67 (d, J=2.1 Hz, 1H) 7.28 (d, J=2.1 Hz, 1H) 8.72 (br. s., 1H).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US07741327B2uspto-grants-2010_06