Triethylamine → 3-(Butylamino)-5-(pyridin-4-yl)thiophene-2-carboxamide

HRID 2363953Notes

Reaction equation

HRID 2363953 reaction equation
[CH2:1]([NH:5][C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)[S:8][C:7]=1[C:17]([OH:19])=O)[CH2:2][CH2:3][CH3:4].[Cl-].[NH4+].C([N:24](CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>O.CN(C=O)C>[CH2:1]([NH:5][C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)[S:8][C:7]=1[C:17]([NH2:24])=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667438043-(Butylamino)-5-(pyridin-4-yl)thiophene-2-carboxylic acid

Product 1

HCID 667440183-(Butylamino)-5-(pyridin-4-yl)thiophene-2-carboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(butylamino)-5-(pyridin-4-yl)thiophene-2-carboxylic acid (0.370 g, 1.34 mmol), ammonium chloride (0.717 g, 13.4 mmol), triethylamine (1.88 mL, 13.4 mmol) and DMF (8.0 mL) was stirred for 5 min. Then, 1-hydroxybenzotriazole (0.541 g, 4.00 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.767 g, 4.00 mmol) were added and stirring was continued for 3 days. The mixture was then poured into sat. aqueous sodium hydrogen carbonate (100 mL) and water (60 mL). Extraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL), washing with sat. aqueous sodium hydrogen carbonate and brine, drying over magnesium sulfate, filtration and concentration at reduced pressure gave a yellow solid. This solid was triturated with dichloromethane, and the precipitate was collected by filtration to afford the title compound (0.202 g, 55%) as a yellow solid. The filtrate was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to ethyl acetate) to afford the additional title compound (0.067 g, 18%):

Workup

  1. stirringstirring
  2. waitwas continued for 3 days
  3. extractionExtraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL)
  4. washwashing with sat. aqueous sodium hydrogen carbonate and brine
  5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
  6. customgave a yellow solid
  7. customThis solid was triturated with dichloromethane
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-d7abf35500d8473f891eeb14c316bf08
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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