Pyrrole-2-carboxaldehyde → HCID 71815317, compound

HRID 1844112Notes

Reaction equation

HRID 1844112 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[CH2:26]2.[NH:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[CH:38]=O.N1CCCC1>ClCCl.CN(C=O)C.C(O)C>[NH:33]1[CH:37]=[CH:36][CH:35]=[C:34]1/[CH:38]=[C:26]1\[C:27](=[O:32])[NH:28][C:29]2[C:25]\1=[CH:24][C:23]([NH:22][C:14]([C:10]1[C:9](=[O:17])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH:13]=[CH:12][CH:11]=1)=[O:16])=[CH:31][CH:30]=2

Participants

9

Reactant 5

HCID 13854Pyrrole-2-carboxaldehydeHCID 24386Thionyl ChlorideHCID 31268PyrrolidineHCID 27732135-Amino-2-oxindoleHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Product 1

HCID 71815317HCID 71815317, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (75 mg, 0.32 mmol) was chlorinated by thionyl chloride (0.1 mL, 1.38 mmol) in the presence of DMF in dichloromethane (10 mL). Reaction mixture was healed to reflux for 2 h. Solvent and excess thionyl chloride was removed in vacuo. Resultant residue was made to react to 5-aminooxindole (50 mg, 0.41 mmol) in the presence of TEA (0.2 mL, 1.43 mmol) in DMF (5 mL) under RT for 1 h. Crude product extracted by ethyl acetate (EA), washed with brine (50 mL). Residue after solvent removal was made to react with pyrrole-2-carboxaldehyde (32 mg, 0.37 mmol) in the presence of catalytic pyrrolidine in ethanol under reflux for 10 h. The solid product was collected by suction filtration, washed with ethanol. Prolonged drying in vacuo yielded the title compound D104: YD: 30% (over 3 steps); mp>300° C. 1H-NMR (400 MHz, DMSO-d6): 13.30 (s, 1H), 11.92 (s, 1H), 10.84 (s, 1H), 8.56 (dd, J=7.2, 2 Hz, 1H), 8.07 (dd, J=6.6, 2 Hz, 1H), 7.92 (d, J=1.6 Hz, 1H), 7.76 (s, 1H), 7.61-7.54 (m, 3H), 7.43 (d, J=8.4, 1.6 Hz, 2H), 7.34 (s, 1H), 6.85-6.83 (m, 2H), 6.71 (dd, J=7.2, 6.8 Hz, 1H), 6.34 (s, 1H). MS (ESI): 439 (M−H)−. (C25H17FN4O3) C, H, N.

Workup

  1. customReaction mixture
  2. temperatureto reflux for 2 h
  3. customSolvent and excess thionyl chloride was removed in vacuo
  4. extractionCrude product extracted by ethyl acetate (EA)
  5. washwashed with brine (50 mL)
  6. customResidue after solvent removal
  7. temperatureunder reflux for 10 h
  8. filtrationThe solid product was collected by suction filtration
  9. washwashed with ethanol
  10. customProlonged drying in vacuo

Sources & evidence

ORD record
ord-6c8ff1b7a5e34ba9ac20fce01cc00f8e
Source dataset
uspto-grants-2015_02
Patent number
US08946282B2

Reaction notes

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