1,1'-Carbonyldiimidazole → HCID 489423, compound

HRID 2395788Notes

Reaction equation

HRID 2395788 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl: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]C>C1COCC1.ClCCl>[CH3:27][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]([Cl:13])=[CH:15][C:16]=3[CH:17]=2)=[O:25])[CH2:38][CH2:37]1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 10331071HCID 10331071, compound

Product 1

HCID 489423HCID 489423, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

1,1'-carbonyldiimidazole (0.42 g) is added to a 20°-25° solution of 5-chloroindole-2-carboxylic acid (I, 0.5 g) in THF (5 ml). After 1 hour of stirring at 20°-25°, the above reaction is added dropwise over 10 minutes via cannula to a -10° (ice/acetone bath) solution of [3-(ethylamino)-2-pyridinyl]piperazine (II, 0.58 g) in THF (5 ml). After 30 minutes of stirring at -10°, the reaction is warmed to 20°-25° and stirring is continued for 5 hours. The reaction is diluted with dichloromethane (50 ml), washed with saturated aqueous sodium bicarbonate (40 ml), water (40 ml) and saline (40 ml). The organic layers are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (50 g silica gel), eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 208°-209°; IR (mineral oil) 3200, 2920-3000, 1632, and 1425 cm-1 ; NMR (300 MHz, CDCl3) 9.77, 7.72, 7.60, 7.36, 7.22, 6.97, 6.86, 6.75, 4.23, 4.09, 3.23-3.15, and 1.33 δ; MS (m/e) 383, 178, 176, 162, 150, 148, 137, 134, and 120.

Workup

  1. customthe above reaction
  2. stirringAfter 30 minutes of stirring at -10°
  3. temperaturethe reaction is warmed to 20°-25°
  4. stirringstirring
  5. waitis continued for 5 hours
  6. washwashed with saturated aqueous sodium bicarbonate (40 ml), water (40 ml) and saline (40 ml)
  7. dry with materialThe organic layers are dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate is purified by flash column chromatography (50 g silica gel)
  10. washeluting with ethyl acetate/hexane (1/1)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6f3bfe6ac22d453b900684f11f67a629
Source dataset
uspto-grants-1996_02
Patent number
US05489593

Reaction notes

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