Pyrrole-2-Carboxylic Acid → (S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-pyrrole-2-carboxamide

HRID 433901Notes

Reaction equation

HRID 433901 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[C:18]([OH:20])=O.[NH2:21][C@H:22]1[CH2:27][C:26]2[C:28]([N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[CH:29][CH:30]=[CH:31][C:25]=2[O:24][CH2:23]1>CN(C)C=O>[CH3:38][N:35]1[CH2:36][CH2:37][N:32]([C:28]2[C:26]3[CH2:27][C@H:22]([NH:21][C:18]([C:14]4[NH:13][CH:17]=[CH:16][CH:15]=4)=[O:20])[CH2:23][O:24][C:25]=3[CH:31]=[CH:30][CH:29]=2)[CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 12473Pyrrole-2-Carboxylic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 53829301(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-pyrrole-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

A mixture of 1,1′-carbonyldiimidazole (360 mg, 1.85 mmol) and pyrrole-2-carboxylic acid (225 mg, 2.03 mmol) in anhydrous N,N-dimethylformamide (8 mL) was stirred at 75° C. for 45 min. The mixture was allowed to cool, and a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (457 mg, 1.85 mmol) in N,N-dimethylformamide (10 mL) was added. The reaction mixture was stirred for 7 days at room temperature under nitrogen. The solvent was removed in vacuo, and the residue was extracted with diethyl ether (50 mL) and water (20 mL). The aqueous layer was extracted with another portion of diethyl ether (50 mL). The combined ethereal layers were dried (MgSO4), and the solvent was removed in vacuo. The residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 90:10+0.5% conc. NH3) yielding the title compound as an oil. Evaporation with diethyl ether afforded 300 mg (48% yield) of the title compound as a white powder: mp sinters >96° C.; [α]21D−82.8° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 340 (10, M+).

Workup

  1. temperatureto cool
  2. stirringThe reaction mixture was stirred for 7 days at room temperature under nitrogen
  3. customThe solvent was removed in vacuo
  4. extractionthe residue was extracted with diethyl ether (50 mL) and water (20 mL)
  5. extractionThe aqueous layer was extracted with another portion of diethyl ether (50 mL)
  6. dry with materialThe combined ethereal layers were dried (MgSO4)
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 90:10+0.5% conc. NH3)

Sources & evidence

ORD record
ord-8a1ea50ae46e463da05cbeb51864e093
Source dataset
uspto-grants-2003_12
Patent number
US06670359B2

Reaction notes

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