Diethyl Ether → (Z)-2-(5-methoxy-1H-indol-3-yl)-3-(1-methyl-1H-pyrazol-3-yl)-acrylonitrile

HRID 1503137Notes

Reaction equation

HRID 1503137 reaction equation
C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:15][C:16]#[N:17].[CH3:18][N:19]1[CH:23]=[C:22](C=O)[CH:21]=[N:20]1.[CH2:26](OCC)C>C(O)C>[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2/[C:15](=[CH:26]/[C:21]1[CH:22]=[CH:23][N:19]([CH3:18])[N:20]=1)/[C:16]#[N:17]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 5731171-Methyl-1H-pyrazole-4-carbaldehydeHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 136041732(Z)-2-(5-methoxy-1H-indol-3-yl)-3-(1-methyl-1H-pyrazol-3-yl)-acrylonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of sodium methanolate (204 mg, 3.8 mmol, 1.4 eq.) in anhydrous ethanol (30 mL) were added, under an argon atmosphere, (5-methoxy-1H-indol-3-yl)-acetonitrile (500 mg, 2.7 mmol, 1.0 eq.) and, after 30 minutes stirring, 1-methyl-1H-pyrazole-4-carbaldehyde (326 mg, 3.0 mmol, 1.1 eq.). The reaction apparatus was protected from light and the mixture heated at 50° C. for 18 hours. The reaction was allowed to cool to room temperature and then, the solvent was removed under reduced pressure and the crude taken up in ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4 and then, evaporated. The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1 to 98/2) to afford, after trituration with diethyl ether, the compound (51) as a beige powder (640 mg, 85%). mp: 178° C.; 1H NMR (DMSO, 300 MHz) δ (ppm): 3.81 (3H, s, 5′-methoxy), 3.92 (3H, s, N-methyl), 6.90 (1H, dd, J6′-7′=8.7 Hz, J6′-4′=2.3 Hz, H6′), 7.37 (1H, d, J7′-6′=8.7 Hz, H7′), 7.38 (1H, m, H4′), 7.55 (1H, s, H3), 7.61 (1H, s, H2′), 8.00 (1H, s, H3″), 8.24 (1H, s, H5″), 11.43 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 38.8 (N-methyl), 55.6 (5′-methoxy), 101.5 (C2), 101.5 (C4′), 109.8 (C3′), 111.9 (C6′), 112.9 (C7′), 117.4 (C4″), 119.3 (C1), 124.0 (C3a′), 125.6 (C2′), 128.5 (C3), 131.0 (C5″), 132.1 (C7a′), 138.8 (C3″), 154.1 (C5′); MS: ESI-MS: m/z 264.1 ([M+H]+), 286.1 ([M+Na]+); HRESI-MS: m/z 301.1060 (calcd for C16H14N4ONa+, 301.1065); Anal. Calcd for C19H14N4O, 0.1H2O: C, 68.61; H, 5.11; N, 20.00; O, 6.55. Found: C, 68.73; H, 5.33; N, 19.69.

Workup

  1. temperatureto cool to room temperature
  2. customthe solvent was removed under reduced pressure
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1 to 98/2)
  7. customto afford

Sources & evidence

ORD record
ord-f79170679aa04a699361c9506f28726e
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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