Hydrochloric Acid → HCID 66743310, compound

HRID 2364086Notes

Reaction equation

HRID 2364086 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7](OC)=[O:8])=[C:4]([NH:11][CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:3]=1.[OH-].[Na+].Cl.C([N:24](CC)CC)C.[Cl-].[NH4+].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CO.O.CCOC(C)=O>[Br:1][C:2]1[S:6][C:5]([C:7]([NH2:24])=[O:8])=[C:4]([NH:11][CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:3]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66744226HCID 66744226, compound

Product 1

HCID 66743310HCID 66743310, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 5-bromo-3-[(pyridin-3-ylmethyl)amino]thiophene-2-carboxylate (260 mg, 0.795 mmol) in MeOH (3 mL) was added a solution of sodium hydroxide (96 mg, 2.39 mmol) in water (1.5 mL). After stirring at 80° C. for 5 h, 6 M aqueous HCl (0.25 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was suspended with DMF (5 mL). Then, triethylamine (2.2 mL, 16 mmol) and ammonium chloride (850 mg, 16 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (914 mg, 4.8 mmol) and 1-hydroxybenzotriazole (645 mg, 4.8 mmol) were added to the mixture, and the stirring was continued for 18 h. Then, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc) to give the title compound (175 mg, 71%) as a yellow solid:

Workup

  1. customAfter removal of the solvent at reduced pressure
  2. stirringAfter stirring at room temperature for 5 min
  3. waitthe stirring was continued for 18 h
  4. customto quench
  5. customthe reaction
  6. extractionThe organic materials were extracted with EtOAc
  7. washThe combined extracts were washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customAfter removal of the solvent at reduced pressure
  11. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc)

Sources & evidence

ORD record
ord-ef8019321e40493ba0119ccf53e8d92f
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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