Reaktion #1269872

ord-5d3525e1d1f34ae3939160f2002a5635

Reaktionsgleichung

COc1cnc(-n2cnc(C)n2)c2[nH]cc(C(=O)C(=O)O)c12
2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid
c1ccc(-n2nnnc2N2CC3(CNC3)C2)cc1
2-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptane
CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.F[P-](F)(F)(F)(F)F
BOP reagent
CCN(C(C)C)C(C)C
Hunig's base
COc1cnc(-n2cnc(C)n2)c2[nH]cc(C(=O)C(=O)N3CC4(C3)CN(c3nnnn3-c3ccccc3)C4)c12
1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(6-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)ethane-1,2-dione
Ausbeute 34.4%

Lösungsmittel

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe mixture was quenched with methanol (10 mL) and volatiles
  2. 2
    Sonstigewere removed under reduced pressure
  3. 3
    workup.ADDITIONThe resulting oil was diluted with ethyl acetate (50 mL)
  4. 4
    Waschenwashed with 10% NaHCO3 (10 mL) and brine (10 mL)
  5. 5
    TrocknenThe organic layer was dried over anhydrous Na2SO4
  6. 6
    Einengenconcentrated under reduced pressure
  7. 7
    SonstigeThe resulting crude was purified by silica gel column chromatography

Vorschrift

2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.050 g), 2-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptane (0.044 g), BOP reagent (0.080 g) and Hunig's base (0.2 mL) were mixed in dry DMF (2 mL). The reaction mixture was stirred at room temperature for 16 hours. The mixture was quenched with methanol (10 mL) and volatiles were removed under reduced pressure. The resulting oil was diluted with ethyl acetate (50 mL), washed with 10% NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude was purified by silica gel column chromatography using MeOH/CHCl3 (1:9) as an eluent to afford 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(6-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)ethane-1,2-dione (30 mg). 1H NMR (400 MHz, DMSO-d6): δ ppm 2.47-2.49 (s, 3H), 3.93 (s, 4H), 4.08-4.13 (m, 2H), 4.20-4.36 (d, 2H), 7.54-7.62 (m, 5H), 7.84 (s, 1H), 8.30-8.32 (s, 1H), 9.22 (s, 1H), 12.26 (bs, 1H). LCMS MS (M+H)+ Calcd.: 526, Observ.: 526.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08664213B2uspto-grants-2014_03