Diethyl Ether → HCID 49855062, compound

HRID 1503128Notes

Reaction equation

HRID 1503128 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][C:10]([CH3:15])=[C:9]2[CH2:16][C:17]#[N:18].[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=O)[CH:20]=1.C(OCC)C>C(O)C.ClCCl>[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([CH3:15])=[C:9]2/[C:16](=[CH:25]/[C:21]1[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=1)/[C:17]#[N:18]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 103713-PyridinecarboxaldehydeHCID 10703201HCID 10703201, compoundHCID 10942334Sodium Methoxide

Product 1

HCID 49855062HCID 49855062, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of sodium methanolate (162 mg, 3.0 mmol, 2.0 eq.) in anhydrous ethanol (20 mL) were added, under an argon atmosphere, (5-methoxy-2-methyl-1H-indol-3-yl)-acetonitrile (300 mg, 1.5 mmol, 1.0 eq.) and, after 30 minutes stirring, pyridine-3-carbaldehyde (352 μL, 3.8 mmol, 2.5 eq.). The reaction apparatus was protected from light and the mixture heated at 50° C. for 12 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: heptane/EtOAc, 40/60) to afford, after trituration with diethyl ether and dichloromethane, the compound (35) as a yellow solid (250 mg, 58%). IR □max (cm−1): 2212 (νCN); 1H NMR (DMSO, 300 MHz) δ (ppm): 2.54 (3H, s, 2′-methyl), 3.77 (3H, s, 5′-methoxy), 6.78 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.4 Hz, H6′), 7.18 (1H, d, J4′-6′=2.4 Hz, H4′), 7.27 (1H, d, J7′-6′=8.9 Hz, H7′), 7.50 (1H, s, H3), 7.55 (1H, dd, J5″-4″=8.1 Hz, J5″-6″=4.8 Hz, H5″), 7.74 (1H, s, H3), 8.35 (1H, d, J4″-5″=8.1 Hz, H4″), 8.61 (1H, d, J6″-5″=4.8 Hz, H6″), 8.97 (1H, s, H2″), 11.45 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) δ (ppm): 12.6 (2′-methyl), 55.3 (5′-methoxy), 100.4 (C4′), 106.1 (C2), 106.9 (C3′), 110.9 (C6′), 111.9 (C7′), 118.0 (C1), 123.7 (C5″), 126.2 (C3a′), 129.9 (C2′), 130.5 (C3″), 134.6 (C3), 136.3 (C7a′), 137.6 (C4″), 149.8 (C6″), 150.0 (C2″), 154.1 (C5′); ESI-MS: m/z 290.1 ([M+H]+), 312.1 ([M+Na]+); HRESI-MS: m/z 290.1299 (calcd for C18H16N3O+, 290.1293).

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: heptane/EtOAc, 40/60)
  7. customto afford

Sources & evidence

ORD record
ord-4df29aaf77a14c31ad2f213c33939ffd
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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