5-Fluoroindole-2-carboxylic acid → HCID 489422, Verbindung

HRID 864434Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 864434
C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18]([C:23]([OH:25])=O)=[CH:17]2.[CH2:26]([NH:29][C:30]1[C:31]([N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[N:32][CH:33]=[CH:34][CH:35]=1)[CH2:27][CH3:28]>C1COCC1.ClCCl>[CH3:28][CH2:27][CH2:26][NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[N:32][C:31]=1[N:36]1[CH2:41][CH2:40][N:39]([C:23]([C:18]2[NH:19][C:20]3[CH:21]=[CH:22][C:14]([F:13])=[CH:15][C:16]=3[CH:17]=2)=[O:25])[CH2:38][CH2:37]1

Komponenten

6

Edukt 3

HCID 18205-Fluoroindole-2-carboxylic acidHCID 682631,1'-CarbonyldiimidazoleHCID 10331071HCID 10331071, Verbindung

Produkt 1

HCID 489422HCID 489422, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

1,1'-carbonyldiimidazole (0.48) is added to a 20°-25° solution of 5-fluoroindole-2-carboxylic acid (I, 0.53 g) in THF (6 ml). After 1 hour of stirring the above reaction is added dropwise via cannula to a solution of [3-(propylamino)-2-pyridinyl]piperazine (II, PREPARATION 7, 0.72 g) in THF (6 ml) at -10° (ice/acetone bath). The reaction is stirred for 30 minutes at -10°, slowly warming to 20°-25°, and stirred 4 hours. The reaction is diluted with dichloromethane (50 ml), washed with saturated aqueous sodium bicarbonate (40 ml), saline (40 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (40 g silica gel) eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 196°-198°; IR (mineral oil) 3200, 2920-3000, 1630 and 1424 cm-1 ; NMR (300 MHz, CDCl3) 9.82, 7.72, 7.35, 7.27, 7.03, 6.95, 6.86, 6.78, 4.32, 4.09, 3.21, 3.08, 1.71 and 1.05 δ; CMR (300 MHz, CDCl3) 162.3, 159.5, 149.7, 137.4, 135.1, 132.3, 130.7, 127.5, 127.4, 120.4, 116.3, 113.4, 112.9, 112.7, 112.5, 106.1, 105.8, 105.1, 105.0, 49.0, 45.2, 22.5 and 11.6 δ; MS (m/e) 382, 381, 190, 176, 164, 162, 134 and 120.

Aufarbeitung

  1. customthe above reaction
  2. stirringThe reaction is stirred for 30 minutes at -10°
  3. temperatureslowly warming to 20°-25°
  4. stirringstirred 4 hours
  5. washwashed with saturated aqueous sodium bicarbonate (40 ml), saline (40 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe concentrate is purified by flash column chromatography (40 g silica gel)
  9. washeluting with ethyl acetate/hexane (1/1)
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-5141401d1c8344e09ab9e3ef4c282ae5
Quelldatensatz
uspto-grants-1996_10
Patentnummer
US05563142

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