Hydrochloric Acid → HCID 66743752, compound

HRID 2364066Notes

Reaction equation

HRID 2364066 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:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=2)[CH:3]=1.[OH-].[Na+].Cl.C([N:27](CC)CC)C.[Cl-].[NH4+].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CO.O>[Br:1][C:2]1[S:6][C:5]([C:7]([NH2:27])=[O:8])=[C:4]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=2)[CH:3]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66743305HCID 66743305, compound

Product 1

HCID 66743752HCID 66743752, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 5-bromo-3-[(3-nitrobenzyl)amino]thiophene-2-carboxylate (495 mg, 1.33 mmol) in MeOH (4 mL) was added a solution of sodium hydroxide (160 mg, 3.99 mmol) in water (2 mL). After stirring at 60° C. for 4 h, 6 M aqueous HCl (0.42 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was diluted with DMF (6 mL). Then, triethylamine (3.7 mL, 27 mmol) and ammonium chloride (1.4 g, 27 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.5 g, 8.0 mmol) and 1-hydroxybenzotriazole (1.1 g, 8.0 mmol) were added to the mixture, and stirring was continued for 17 h. Then, water was 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, hexane to 50:50 hexane/EtOAc) to give the title compound (269 mg, 57%) as a yellow solid:

Workup

  1. customAfter removal of the solvent at reduced pressure
  2. additionthe residue was diluted with DMF (6 mL)
  3. stirringAfter stirring at room temperature for 5 min
  4. stirringstirring
  5. waitwas continued for 17 h
  6. customto quench
  7. customthe reaction
  8. extractionThe organic materials were extracted with EtOAc
  9. washThe combined extracts were washed with water and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. customAfter removal of the solvent at reduced pressure
  13. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 50:50 hexane/EtOAc)

Sources & evidence

ORD record
ord-2039098fb9124a2dacdba67a6f0d97b1
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

Loading…