5-Fluoroindole-2-carboxylic acid → HCID 489438, compound

HRID 864439Notes

Reaction equation

HRID 864439 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:26][NH:27][C:28]1[C:29]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[N:30][CH:31]=[CH:32][CH:33]=1>C1COCC1.C(OCC)(=O)C>[CH3:26][NH:27][C:28]1[CH:33]=[CH:32][CH:31]=[N:30][C:29]=1[N:34]1[CH2:39][CH2:38][N:37]([C:11]([C:6]2[NH:7][C:8]3[CH:9]=[CH:10][C:2]([F:1])=[CH:3][C:4]=3[CH:5]=2)=[O:13])[CH2:36][CH2:35]1

Participants

6

Reactant 3

HCID 18205-Fluoroindole-2-carboxylic acidHCID 682631,1'-CarbonyldiimidazoleHCID 19418881HCID 19418881, compound

Product 1

HCID 489438HCID 489438, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

5-Fluoroindole-2-carboxylic acid (98 mg) and 1,1'-carbonyldiimidazole (95 mg) are dissolved in dry THF (1 ml) and stirred for 2 hr at 20°-25°. The resulting solution is added via canula to a -10° cooled solution of 4-[3-(methylamino)-2-pyridinyl]piperazine (117 mg) in dry THF (1 ml). The reaction mixture is then allowed to reach 20°-25° overnight. The reaction mixture is then diluted with ethyl acetate, washed with saturated sodium bicarbonate and saline, dried over magnesium sulfate, and concentrated to give a solid, which is purified on a silica gel flash column eluting with hexane/ethyl acetate (1/1). The appropriate fractions are pooled and concentrated to give a solid. Recrystallization of the solid from ethyl acetate/ether gives the title compound, mp 194°-195°.

Workup

  1. additionThe resulting solution is added via canula to a -10°
  2. waitto reach 20°-25° overnight
  3. washwashed with saturated sodium bicarbonate and saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give a solid, which
  7. customis purified on a silica gel flash column
  8. washeluting with hexane/ethyl acetate (1/1)
  9. concentrationconcentrated
  10. customto give a solid
  11. customRecrystallization of the solid from ethyl acetate/ether

Sources & evidence

ORD record
ord-4bd0a96118b345558a1e7fe2348c819a
Source dataset
uspto-grants-1996_10
Patent number
US05563142

Reaction notes

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