1-Hydroxybenzotriazole → N-(pyrrolidin-3-yl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide

HRID 73250

反応式

HRID 73250 の反応式
Cl.C(N=C=[N:6][CH2:7][CH2:8][CH2:9][N:10]([CH3:12])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].ON1C2C=CC=CC=2N=N1.N1CCC(N)C1>O.CN(C=O)C.C(N(CC)CC)C>[NH:10]1[CH2:9][CH2:8][CH:7]([NH:6][C:21]([C:17]2[C:16]([CH3:24])=[C:15]([CH:13]=[O:14])[NH:19][C:18]=2[CH3:20])=[O:23])[CH2:12]1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 1644013-AminopyrrolidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid

生成物 1

HCID 86659140N-(pyrrolidin-3-yl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide収率 68%

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
0 °C

実験手順

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 pyrrolidine-3-amine (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 159.8 g (680 mmol) of N-(pyrrolidin-3-yl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-formamide as an off-white solid. Yield 68.0%.

後処理

  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)

出典と根拠

ORDレコード
ord-ae13777eb3014ac28991043e1b160aec
出典データセット
uspto-grants-2014_09
特許番号
US08829039B2

関連ノート

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