1-Hydroxybenzotriazole → N-[(piperidin-4-yl)methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73249Notes

Reaction equation

HRID 73249 reaction equation
Cl.[CH2:2]([N:4]=C=NCCCN(C)C)C.[CH:13]([C:15]1[NH:19][C:18]([CH3:20])=[C:17]([C:21]([OH:23])=O)[C:16]=1[CH3:24])=[O:14].O[N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34]C=2N=N1.N1CCC(NC)CC1>O.CN(C=O)C.C(N(CC)CC)C>[NH:26]1[CH2:30][CH2:31][CH:32]([CH2:2][NH:4][C:21]([C:17]2[C:16]([CH3:24])=[C:15]([CH:13]=[O:14])[NH:19][C:18]=2[CH3:20])=[O:23])[CH2:33][CH2:34]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic AcidHCID 21973737N-Methyl-4-piperidinamine

Product 1

HCID 86659139N-[(piperidin-4-yl)methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamideYield 60.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (268.1 g, 1.4 mol), triethylamine (280.0 mL), 5-formyl-2,4-dimethyl-1H-pyrrole-3-formic acid (167.0 g, 1.0 mol) and 1-hydroxybenzotriazole (189.2 g, 1.4 mol) were added to DMF (500 mL) with stirring at about 0° C. and stirred for 1.5 hrs, then piperidin-4-yl-methylamine (1.2 mol) was added. The reaction was stirred at room temperature until completion was indicated by thin layer chromatography (TLC). 120 mL of water and 100 mL of saturated salt water were added, and the mixture was extracted with 10% methanol/dichloromethane (300 mL×3), the combined organic phase was washed with saturated salt water (300 mL×3), dried over anhydrous Na2SO4, and the solvent was distilled off under reduced pressure. The residue was then chromatographed on silica gel (eluted with methanol/ethyl acetate=1/1) to give 158.3 g (602 mmol) of N-[(piperidin-4-yl)methyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide as an off-white solid. Yield 60.2%.

Workup

  1. stirringstirred for 1.5 hrs
  2. stirringThe reaction was stirred at room temperature until completion
  3. extractionthe mixture was extracted with 10% methanol/dichloromethane (300 mL×3)
  4. washthe combined organic phase was washed with saturated salt water (300 mL×3)
  5. dry with materialdried over anhydrous Na2SO4
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was then chromatographed on silica gel (eluted with methanol/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-4128d9683b5748a7938ca050b2add3ab
Source dataset
uspto-grants-2014_09
Patent number
US08829039B2

Reaction notes

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