Diethyl Ether → HCID 49853607, Verbindung

HRID 2368857Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2368857
[C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6](C(OC(C)(C)C)=O)[CH:5]=1)#[N:2].[H-].[Na+].[F:24][C:25]1[C:30]([CH:31]=O)=[CH:29][CH:28]=[CH:27][N:26]=1.C(OCC)C>C1COCC1>[F:24][C:25]1[C:30](/[CH:31]=[C:3](/[C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=3)[NH:6][CH:5]=2)\[C:1]#[N:2])=[CH:29][CH:28]=[CH:27][N:26]=1

Komponenten

6

Edukt 4

HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 114349442-Fluoropyridine-3-carbaldehydeHCID 11616206tert-Butyl 3-(cyanomethyl)-5-methoxy-1H-indole-1-carboxylate

Produkt 1

HCID 49853607HCID 49853607, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of tert-butyl 3-(cyanomethyl)-5-methoxy-1H-indol-1-carboxylate (719 mg, 2.51 mmol, 1.0 eq.) in anhydrous THF (30 mL) was added, under an argon atmosphere, NaH (106 mg, 80%, 3.52 mmol, 1.4 eq.). The mixture was stirred at room temperature for 2 hours, and then cooled to 0° C. before the addition of 2-fluoro-pyridine-3-carbaldehyde (440 mg, 3.52 mmol, 1.4 eq.) in anhydrous THF (6 mL). The reaction apparatus was protected from light and the mixture was stirred at 0° C. for 24 hours, at room temperature for 24 hours too and then, quenched with a saturated aqueous ammonium chloride solution. The mixture was stirred again at room temperature for 24 hours and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98/2) to afford, after trituration with diethyl ether, the compound (48) as a yellow powder (220 mg, 30%). IR νmax (cm−1): 2219 (νCN), 3228 (νN—H); 1H NMR (DMSO, 300 MHz): δ (ppm): 3.81 (3H, s, 5′-methoxy), 6.91 (1H, dd, J6′-7′=8.9 Hz, J6′-4′=2.1 Hz, H6′), 7.42 (1H, d, J7′-6′=8.9 Hz, H7′), 7.43 (1H, d, J4′-6′=2.4 Hz, H4′), 7.53 (1H, m, H5″), 7.64 (1H, s, H3), 7.84 (1H, s, H2′), 8.29 (1H, d, J6″-5″=4.5 Hz, H6″), 8.49 (1H, m, H4″), 11.73 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): δ (ppm): 55.5 (5′-methoxy), 101.5 (C4′), 109.8 (C2), 110.0 (C3′), 112.5 (C6′), 113.3 (C7′), 117.3 (C1), 118.0 (1C, d, 2JC—F=28 Hz, C3″), 122.3 (1C, d, 4JC—F=4 Hz, C5″), 123.9 (C3a′), 125.8 (C3), 128.1 (C2′), 132.2 (C7a′), 139.4 (1C, d, 3JC—F=3 Hz, C4″), 147.5 (1C, d, 3JC—F=15 Hz, C6″), 154.7 (C5′), 159.7 (1C, d, 1JC—F=270 Hz, C2″); ESI: 294.1 ([M+H]+), 316.1 ([M+Na]+), 348.1 ([M+Na+MeOH]+); HRESI-MS: m/z 316.0861 (calcd for C17H12N3OFNa+, 316.0862).

Aufarbeitung

  1. stirringthe mixture was stirred at 0° C. for 24 hours, at room temperature for 24 hours too
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. stirringThe mixture was stirred again at room temperature for 24 hours
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 98/2)
  9. customto afford

Quellen und Nachweise

ORD-Eintrag
ord-94b6bad428e34aed9ac3703d17039a6a
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703808B2

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