Tetrahydrofuran → 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 4-((E)-2-carboxy-vinyl)-phenyl ester

HRID 1008125Notes

Reaction equation

HRID 1008125 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1/[CH:8]=[C:9]1\[C:10](=[O:25])[N:11]([C:18](N2C=CN=C2)=[O:19])[C:12]2[C:17]\1=[CH:16][CH:15]=[CH:14][CH:13]=2.[C:26]([OH:36])(=[O:35])[CH:27]=[CH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1C[O:40]CC1>C(N(CC)CC)C>[C:26](/[CH:27]=[CH:28]/[C:29]1[CH:30]=[CH:31][C:32]([O:40][C:18]([N:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)/[C:9](=[CH:8]/[C:3]3[NH:4][C:5]([CH3:7])=[CH:6][C:2]=3[CH3:1])/[C:10]2=[O:25])=[O:19])=[CH:33][CH:34]=1)([OH:36])=[O:35]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 87842-Propenoic acid, 3-phenyl-HCID 601112313-[1-(3,5-Dimethyl-1h-pyrrol-2-yl)-meth-(z)-ylidene]-1-(imidazol-1-ylcarbonyl)-1,3-dihydro-indol-2-one

Product 1

HCID 601112193-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 4-((E)-2-carboxy-vinyl)-phenyl esterYield 16%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineCatalyst

Conditions

Temperature
60 °C

Procedure

A reaction mixture of of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-1-(imidazol-1-ylcarbonyl)-1,3-dihydro-indol-2-one (165 mg, 0.5 mmol), cinnamic acid (85 mg, 0.5 mmol), and 2 drops of triethylamine in 3 mL of THF was stirred at 60° C. for 5 h and room temperature overnight and filtered. The solid was then washed with ethyl acetate and 1 N aqueous hydrogen chloride solution. The filtrate was concentrated and the residue was partitioned between ethyl acetate and water-acetic acid. The organic layer was washed with diluted sodium hydroxide solution, dried over magnesium sulfate, and concentrated. The resultant residue was suspended in warm ethyl acetate and filtered. The combined solid was then dried in a vacuum oven overnight to afford 35 mg (16%) of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 4-((E)-2-carboxy-vinyl)-phenyl ester. 1H NMR (400 MHz, DMSO-d6) δ 12.55 (s, 1H, NH-1′), 12.41 (s, br, 1H, COOH), 7.91-7.94 (m, 1H), 7.82-7.85 (m, 3H), 7.71 (s, 1H, H-vinyl), 7.65 (d, J=6.02 Hz, 1H), 7.44 (d, J=8.99 Hz, 1H), 7.24-7.26 (m, 2H), 6.57 (d, J=6.02 Hz, 1H), 6.15 (d, J=2.35 Hz, 1H, H-4′), 2.39 (s, 3H, CH3), and 2.37 (s, 3H, CH3).

Workup

  1. filtrationfiltered
  2. washThe solid was then washed with ethyl acetate and 1 N aqueous hydrogen chloride solution
  3. concentrationThe filtrate was concentrated
  4. customthe residue was partitioned between ethyl acetate and water-acetic acid
  5. washThe organic layer was washed with diluted sodium hydroxide solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. filtrationfiltered
  9. customThe combined solid was then dried in a vacuum oven overnight

Sources & evidence

ORD record
ord-30e844a182a54f9ab2272ed3b682c156
Source dataset
uspto-grants-2004_09
Patent number
US06797725B2

Reaction notes

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