Water → N-{2-[(piperidin-4-yl)methylamino]-2-oxoethyl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73260Notes

Reaction equation

Cl.C(N=C=N[CH2:7][CH2:8][CH2:9][N:10]([CH3:12])C)C.[CH2:13]([N:15]([CH2:18]C)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].O[N:33]1[C:37]2C=CC=CC=2N=N1.[OH2:42]>CN(C=O)C>[NH:15]1[CH2:18][CH2:7][CH:8]([CH2:9][NH:10][C:12](=[O:42])[CH2:37][NH:33][C:28]([C:24]2[C:23]([CH3:31])=[C:22]([CH:20]=[O:21])[NH:26][C:25]=2[CH3:27])=[O:30])[CH2:14][CH2:13]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 compound obtained in the above step (1.37 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 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 0.682 g (2.13 mmol) of N-{2-[(piperidin-4-yl)methylamino]-2-oxoethyl}-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide. Yield 53.3%. 1HNMR (DMSO-d6) δ10.82 (s, br, 1H, NH), 7.65 (m, br, 1H, CONHCH2), 7.62 (t, br, 1H, NH), 7.58 (m, br, 1H, CONHCH2), 4.41 (s, br, 1H, NH), 3.85-3.80 (d, 2H), 3.67-3.68 (m, 1H), 3.50-3.66 (m, 2H), 3.16-3.17 (m, 2H), 3.02-3.09 (m, 2H), 2.50 (s, 3H), 2.60 (s, 3H), 1.71-1.82 (m, 2H), 1.10-1.11 (m, 2H).

Workup

stirringstirred for 1.5 hrs
customthe compound obtained in the above step (1.37 g, 8 mmol)
additionwas added
stirringThe reaction was stirred at room temperature until completion
extractionthe mixture was extracted with 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-af310bcc80c54344be0f6db56608e2e3
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829039B2

Reaction notes

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