Hydrochloric Acid → HCID 66743876, compound

HRID 2364060Notes

Reaction equation

HRID 2364060 reaction equation
[OH-].[Na+].[Br:3][C:4]1[S:8][C:7]([C:9](OC)=[O:10])=[C:6]([NH:13][CH3:14])[C:5]=1[CH3:15].Cl.[Cl-].[NH4+].C([N:21](CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CO.O>[Br:3][C:4]1[S:8][C:7]([C:9]([NH2:21])=[O:10])=[C:6]([NH:13][CH3:14])[C:5]=1[CH3:15]

Participants

12

Reactant 8

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66743799HCID 66743799, compound

Product 1

HCID 66743876HCID 66743876, compoundYield 56.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Sodium hydroxide (4.27 g, 107 mmol) was dissolved with water (35 mL) and MeOH (140 mL). Then, methyl 5-bromo-4-methyl-3-(methylamino)thiophene-2-carboxylate (4.46 g, 16.7 mmol) was added to the mixture. The mixture was stirred at 70° C. overnight. After cooling in ice-water bath, 6 M HCl (11.9 mL, 71.4 mmol) was added, and the mixture was concentrated under reduced pressure. The residue was co-evaporated with toluene twice to give a yellow solid. This residue was mixed with ammonium chloride (38.1 g, 712 mmol), triethylamine (99 mL, 712 mmol) and DMF (300 mL), and the mixture was stirred for 5 min. Then, 1-hydroxybenzotriazole (32.7 g, 214 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (40.9 g, 214 mmol) were added to the mixture, and stirring was continued for 3 days. The reaction mixture was poured into saturated aqueous NaHCO3 (1 L). Extraction with EtOAc (1 L), washing with saturated NaHCO3, drying over MgSO4, filtration and concentration under reduced pressure gave a brown oil. This oil was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to afford the title compound (2.34 g, 56%) as a brown oil:

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customto give a yellow solid
  3. stirringthe mixture was stirred for 5 min
  4. stirringstirring
  5. waitwas continued for 3 days
  6. extractionExtraction with EtOAc (1 L)
  7. washwashing with saturated NaHCO3
  8. dry with materialdrying over MgSO4, filtration and concentration under reduced pressure
  9. customgave a brown oil
  10. customThis oil was purified by column chromatography (Purif, silica gel, hexane to EtOAc)

Sources & evidence

ORD record
ord-e566d65048e0472096a0cf4f999e212c
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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