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

HRID 2368848Notes

Reaction equation

HRID 2368848 reaction equation
C([O-])C.[Na+].[CH3:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH2:16][C:17]#[N:18].[CH:19]([C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[C:24]#[N:25])=O>>[C:17](/[C:16](/[C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([O:6][CH3:5])[CH:8]=2)[NH:12][CH:11]=1)=[CH:19]\[C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[C:24]#[N:25])#[N:18]

Participants

4

Reactant 3

HCID 90670m-FormylbenzonitrileHCID 2723922Sodium ethoxideHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrile

Product 1

HCID 49855058(Z)-3-[2-cyano-2-(5-methoxy-1H-indol-3-yl)-vinyl]-benzonitrile

Procedure

To a solution of sodium ethanolate [prepared from sodium (30 mg, 1.3 mmol, 1.2 eq.) and anhydrous ethanol (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 at room temperature for 3 days. The solvent was removed under reduced pressure, and the crude purified by silica gel flash-column chromatography (eluent: heptane/CH2Cl2, 50:50 à 20:80). The residue was triturated with ethanol and diethyl ether to the compound (30) as a yellow powder (110 mg, 34%). mp: 149° C.; IR νmax (cm−1): 2227 (νCN), 3338 (νN—H); 1H NMR (DMSO, 500 MHz) δ (ppm): 3.84 (3H, s, 5′-methoxy), 6.90 (1H, m, H6′), 7.41 (1H, m, H7′), 7.49 (1H, s, H4′), 7.73 (1H, m, H5″), 7.76 (1H, s, H3), 7.79 (1H, s, H2′), 7.88 (1H, m, H6″), 8.24 (1H, m, H″), 8.28 (1H, m, H″), 11.70 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 55.8 (5′-methoxy), 102.2 (C4′), 108.6 and 110.3 (C2 and C3′), 112.0 (C3″), 112.6 (C6′), 113.3 (C7′), 118.0 and 118.6 (C1 and nitrile C), 124.1 (C3a′), 128.1 (C2′), 130.1 (C5″), 132.3 (C6″), 132.4 and 132.5 (C2″, C5″ and C7a′), 133.1 (C3), 136.2 (C1″), 154.8 (C5′); ESI-MS: m/z 322.1 ([M-Na]+); HRESI-MS: m/z 322.0946 (calcd for C19H13N3ONa, 322.0956).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe crude purified by silica gel flash-column chromatography (eluent: heptane/CH2Cl2, 50:50 à 20:80)
  3. customThe residue was triturated with ethanol and diethyl ether to the compound (30) as a yellow powder (110 mg, 34%)

Sources & evidence

ORD record
ord-4ae4068f28e74a3698e010494af61213
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

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