Dimethylformamide → N-{1-[4-(dimethylamino)anilino]-1-oxoprop-2-yl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73253Notes

Reaction equation

Cl.C(N=C=N[CH2:7][CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])C.[CH2:13]([N:15](CC)CC)[CH3:14].[CH:20]([C:22]1[NH:26][C:25]([CH3:27])=[C:24]([C:28]([OH:30])=O)[C:23]=1[CH3:31])=[O:21].ON1[C:37]2C=CC=C[C:36]=2N=N1.[CH3:42][N:43]([CH:45]=[O:46])C>O>[CH3:12][N:10]([CH3:11])[C:9]1[CH:8]=[CH:7][C:42]([NH:43][C:45](=[O:46])[CH:13]([NH:15][C:28]([C:24]2[C:23]([CH3:31])=[C:22]([CH:20]=[O:21])[NH:26][C:25]=2[CH3:27])=[O:30])[CH3:14])=[CH:37][CH:36]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.074 g, 5.6 mmol), triethylamine (1.12 mL, 8 mmol), 5-formyl-2,4-dimethyl-1H-pyrrole-3-formic acid (0.668 g, 4 mmol) and 1-hydroxybenzotriazole (0.756 g, 5.6 mmol) were added to DMF (10 mL) with stirring at about 0° C. and stirred for 1.5 hrs, and the oily residue obtained in the above step (1.66 g, 8 mmol) was added. The reaction was stirred at room temperature until completion was indicated by thin layer chromatography (TLC). 1.2 mL of water and 1 mL of saturated salt water were added, and the mixture was extracted with organic solvents (10% methanol/dichloromethane) (25 mL×3), the combined organic phase was washed with saturated salt water (25 mL×3), dried over anhydrous Na2SO4, and the solvent was distilled off under reduced pressure. The residue was then chromatographed (silica gel column chromatography, eluent: methanol:ethyl acetate=1:2) to give 0.786 g (2.21 mmol) of N-{1-[4-(dimethylamino)anilino]-1-oxoprop-2-yl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide, yield 55.2%. 1HNMR (DMSO-d6) δ 10.83 (s, br, 1H, NH), 9.67 (s, 1H), 9.34 (s, br, 1H, NH), 7.65 (m, br, 1H, CONHCH2), 7.54-7.52 (d, 2H), 6.77-6.74 (d, 2H), 4.71 (m, 1H), 3.38-2.58 (s, 6H), 2.58-2.56 (m, 3H), 2.55-2.41 (m, 3H), 1.48-1.41 (d, 3H).

Workup

stirringstirred for 1.5 hrs
customthe oily residue obtained in the above step (1.66 g, 8 mmol)
additionwas added
stirringThe reaction was stirred at room temperature until completion
extractionthe mixture was extracted with organic solvents (10% methanol/dichloromethane) (25 mL×3)
washthe combined organic phase was washed with saturated salt water (25 mL×3)
dry with materialdried over anhydrous Na2SO4
distillationthe solvent was distilled off under reduced pressure
customThe residue was then chromatographed (silica gel column chromatography, eluent: methanol:ethyl acetate=1:2)

Sources & evidence

ORD record: ord-b6af644116b040929a144bec3319d9da
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829039B2

Reaction notes

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