Diethyl Ether → HCID 49854742, compound

HRID 2368846Notes

Reaction equation

HRID 2368846 reaction equation
C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([CH2:15][C:16]#[N:17])=[CH:9][NH:10]2.[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]=O)[CH:19]=1.C(OCC)C>C(O)C.C(Cl)Cl>[CH3:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](/[C:15](=[CH:24]/[C:20]1[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=1)/[C:16]#[N:17])=[CH:9][NH:10]2

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 103713-Pyridinecarboxaldehyde2×HCID 1194064-Methoxyindole-3-acetonitrileHCID 10942334Sodium Methoxide2×

Product 1

HCID 49854742HCID 49854742, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of sodium methanolate (261 mg, 4.8 mmol, 1.5 eq.) in anhydrous ethanol (40 mL) were added, under an argon atmosphere, of (4-methoxy-1H-indol-3-yl)-acetonitrile (600 mg, 3.2 mmol, 1.0 eq.) and, after 30 minutes stirring, pyridine-3-carbaldehyde (908 μL, 9.7 mmol, 3.0 eq.). The reaction apparatus was protected from light and the mixture heated at 60° C. Several amounts of sodium methanolate (4×1.0 eq.) and pyridine-3-carbaldehyde (4×1.0 eq.) were added after stirring for 24, 48, 72 and 96 hours respectively. The reaction was pursued for 2 days (6 days overall) at 60° C. 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, 98:2 to 97:3) to afford, after trituration with diethyl ether, the compound (27) as a yellow powder (510 mg, 58%). TLC: Rf=0.30 (CH2Cl2 96/EtOH 4); mp: 177° C.; 1H NMR (DMSO, 500 MHz): δ (ppm): 3.90 (3H, s, 4′-methoxy), 6.66 (1H, d, J5′-6′=7.9 Hz, H5′), 7.07 (1H, d, J7′-6′=7.9 Hz, H7′), 7.14 (1H, t, J6′-5′=J6′-7′=7.9 Hz, H6′), 7.55 (1H, dd, J5″-4″=7.9 Hz, J5″-6″=4.9 Hz, H5″), 7.62 (1H, s, H2′), 7.78 (1H, s, H3), 8.31 (1H, d, J4″-5″=7.9 Hz, H4″), 8.59 (1H, d, J6″-5″=4.9 Hz, H6″), 8.91 (1H, s, H2″), 11.67 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.6 (4′-methoxy), 101.4 (C5′), 106.0 (C7′), 108.6 (C2), 111.9 (C3′), 114.7 (C3a′), 119.1 (C1), 124.1 (C5″), 124.3 (C6′), 126.6 (C2′), 131.1 (C3″), 134.9 (C4″), 138.0 (C3), 139.0 (C7a′), 150.3 (C6″), 150.4 (C2″), 153.7 (C4′); ESI-MS: m/z 276.1 ([M+H]+), 298.1 ([M+Na]+); HRESI-MS: m/z 276.1137 (calcd for C17H14N3O, 276.1137).

Workup

  1. stirringafter stirring for 24, 48, 72 and 96 hours respectively
  2. custom(6 days overall) at 60° C. and then, the 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, 98:2 to 97:3)
  7. customto afford

Sources & evidence

ORD record
ord-ee074e5038c44cc5ab18828e82f4619d
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

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