3-Thiophenecarboxaldehyde → (Z)-2-(5-methoxy-1H-indol-3-yl)-3-thiophen-3-yl-acrylonitrile

HRID 2368859Notes

Reaction equation

HRID 2368859 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].[S:18]1[CH:22]=[CH:21][C:20]([CH:23]=O)=[CH:19]1>C(O)C.CCCCCCC.C(OCC)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:23]/[C:20]1[CH:21]=[CH:22][S:18][CH:19]=1)/[C:16]#[N:17]

Participants

7

Reactant 3

HCID 681353-ThiophenecarboxaldehydeHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 49853609(Z)-2-(5-methoxy-1H-indol-3-yl)-3-thiophen-3-yl-acrylonitrile

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8900HeptaneSolvent2×

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, thiophen-3-carbaldehyde (235 μL, 2.7 mmol, 1.0 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) to afford, after trituration with heptane and diethyl ether, the compound (50) as a beige solid (310 mg, 41%). IR νmax (cm−1): 2212 (νCN), 3340 (νN—H); 1H NMR (DMSO, 300 MHz) δ (ppm): 3.82 (3H, s, 5′-methoxy), 6.88 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.4 Hz, H6′), 7.38 (1H, d, J7′-6′=8.9 Hz, H7′), 7.42 (1H, d, J4′-6′=2.4 Hz, H4′), 7.69 (1H, d, J4″-5″=5.1 Hz, H4″), 7.70 (1H, m, H3), 7.72 (1H, m, H2′), 7.79 (1H, dd, J5″-4″=5.1 Hz, J5″-2″=1.3 Hz, H5″), 8.10 (1H, m, H2″), 11.54 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 55.5 (5′-methoxy), 101.7 (C4′), 103.8 (C2), 109.9 (C3′), 112.1 (C6′), 113.0 (C7′), 118.1 (C1), 124.0 (C3a′), 126.5 (C4″ and C5″), 127.3 (C2′), 128.0 (C2″), 130.6 (C3), 132.2 (C7a′), 136.6 (C3″), 154.3 (C5′); ESI-MS: m/z 281.1 ([M+H]+), 303.1 ([M+Na]+); HRESI-MS: m/z 303.0568 (calcd for C16H12N2ONaS+, 303.0568).

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)
  7. customto afford

Sources & evidence

ORD record
ord-57b81b9b40734928a2266bfbe784f7e9
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

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