5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid → 5-(6-benzoylamino-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

HRID 422008Notes

Reaction equation

HRID 422008 reaction equation
[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:7][CH:8]=2)[NH:3]1.[CH:20]([C:22]1[NH:26][C:25]([CH3:27])=[C:24]([C:28]([OH:30])=[O:29])[C:23]=1[CH3:31])=O>C(O)C.N1CCCCC1>[C:12]([NH:11][C:6]1[CH:5]=[C:4]2[C:9]([C:10](=[CH:20][C:22]3[NH:26][C:25]([CH3:27])=[C:24]([C:28]([OH:30])=[O:29])[C:23]=3[CH3:31])[C:2](=[O:1])[NH:3]2)=[CH:8][CH:7]=1)(=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 2

HCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic AcidHCID 219257686-Benzamido-2-oxindole

Product 1

HCID 666753335-(6-benzoylamino-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(2-oxo-2,3-dihydro-1H-indol-6-yl)-benzamide (80 mg, 0.32 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (53 mg, 0.32 mmol) in ethanol (8 ml) is added 4 drops of piperidine. It is stirred at 80° C. for 20 hours and then cooled to room temperature. The precipitate is collected by vacuum filtration, washed with a small amount of cold ethanol to give crude 5-(6-benzoylamino-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid. This carboxylic acid (20 mg, 0.050 mmol) is then dissolved in DMF (1 ml). To this reaction is also added N, N-diethylethylenediamine (17 mg, 0.15 mmol), N,N-diisopropylethylamine (19 mg, 0.15 mmol) and HATU (23 mg, 0.061 mmol). It is stirred for 2 hours and concentrated. The desired compound is obtained after HPLC purification: 1H NMR (DMSO-d6) δ 1.24 (t, 6H, J=7.2 Hz), 2.43 (s, 3H), 2.47 (s, 3H), 3.20-3.24 (m, 6H), 3.57 (q, 2H, J=5.4 Hz), 7.38 (d, 1H, J=6.6 Hz), 7.53 (t, 2H, J=7.2 Hz), 7.56 (s, 1H), 7.58-7.61 (m, 2H), 7.73-7.77 (m, 2H), 7.96 (d, 2H, J=7.8 Hz), 9.32 (s, 1H), 10.27 (s, 1H), 10.97 (s, 1H), 13.60 (s, 1H); LC-MS: 500.2 (MH+).

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe precipitate is collected by vacuum filtration
  3. washwashed with a small amount of cold ethanol

Sources & evidence

ORD record
ord-f3822f9c05e740858b1b913812cf6291
Source dataset
uspto-grants-2012_01
Patent number
US08101608B2

Reaction notes

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