m-Formylbenzonitrile → (Z)-3-[2-cyano-2-(5-methoxy-1H-indol-3-yl)-vinyl]-benzamide

HRID 2368849Notes

Reaction equation

HRID 2368849 reaction equation
C([O-:4])(C)C.[Na+].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C:18]#[N:19].[CH:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[C:25]#[N:26])=O>>[C:18](/[C:17](/[C:11]1[C:10]2[C:14](=[CH:15][CH:16]=[C:8]([O:7][CH3:6])[CH:9]=2)[NH:13][CH:12]=1)=[CH:20]\[C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[C:25]([NH2:26])=[O:4])#[N:19]

Participants

4

Reactant 3

HCID 90670m-FormylbenzonitrileHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrileHCID 109204432-Propanol, sodium salt (1:1)

Product 1

HCID 49855060(Z)-3-[2-cyano-2-(5-methoxy-1H-indol-3-yl)-vinyl]-benzamide

Procedure

To a solution of sodium isopropanolate [prepared from sodium (30 mg, 1.3 mmol, 1.2 eq.) and isopropanol (8 mL)] were added, under an argon atmosphere, (5-methoxy-1H-indol-3-yl)-acetonitrile (200 mg, 1.1 mmol, 1.0 eq.) and, after 10 minutes stirring, 3-formyl-benzonitrile (200 mg, 1.5 mmol, 1.4 eq.). The reaction apparatus was protected from light and the mixture stirred heated at reflux for 4 hours. The reaction was allowed to cool to room temperature and then, the solvent was removed under reduced pressure, and the crude purified by silica gel flash-column chromatography (eluent: CH2Cl2/MeOH, 100:0 à 97:3). The residue was triturated with ethanol and diethyl ether to the compound (32) as a yellow powder (80 mg, 24%). TLC: Rf=0.34 (CH2Cl2 96/MeOH 4); mp: 234° C.; IR νmax (cm−1): 1651 (νC═O), 2215 (νCN), 3172 (νN—H amide), 3326 (νN—H indole); 1H NMR (DMSO, 300 MHz) δ (ppm): 3.89 (3H, s, 5′-methoxy), 6.97 (1H, m, H6′), 7.48 (2H, s, H7′ and amide H), 7.53 (1H, s, H4′), 7.65 (1H, m, H5″), 7.83 (2H, s, H3 and H2′), 7.95 (1H, m, H4″), 8.12 (2H, m, H6″ and amide H), 8.39 (1H, m, H2″), 11.68 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 55.6 (5′-methoxy), 101.8 (C4′), 107.0 and 110.3 (C2 and C3′), 112.3 (C6′), 113.2 (C7′), 118.3 (C1), 124.1 (C3a′), 127.3 (C2′), 127.9 (C4″), 128.3 (C2″), 128.7 (C5″), 130.5 (C6″), 132.3 (C7a′), 134.9 (C1″ and C3″), 135.5 (C3), 154.5 (C5′), 167.7 (amide C); ESI-MS: m/z 340.1 ([M+Na]+), 316.1 ([M−H]−); HRESI-MS: m/z 340.1067 (calcd for C19H15N3O2Na), m/z 316.1117 (calcd for C19H14N3O2, 316.1086).

Workup

  1. temperatureheated
  2. temperatureat reflux for 4 hours
  3. customthe solvent was removed under reduced pressure
  4. customthe crude purified by silica gel flash-column chromatography (eluent: CH2Cl2/MeOH, 100:0 à 97:3)
  5. customThe residue was triturated with ethanol and diethyl ether to the compound (32) as a yellow powder (80 mg, 24%)

Sources & evidence

ORD record
ord-48b62561f14a449197708fc52128f28d
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

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