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

HRID 2395787Notes

Reaction equation

HRID 2395787 reaction equation
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

Participants

6

Reactant 3

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

Product 1

HCID 489422HCID 489422, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

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 for 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, 105.8, 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.

Workup

  1. customthe above reaction
  2. stirringThe reaction is stirred for 30 minutes at -10°
  3. temperatureslowly warming to 20°-25°
  4. stirringstirred for 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

Sources & evidence

ORD record
ord-507ca5430222472ea7b7d86c11fc7f3b
Source dataset
uspto-grants-1996_02
Patent number
US05489593

Reaction notes

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