Triethylamine → 7-Chloroisoquinolin-3-amine

HRID 1257113Notes

Reaction equation

HRID 1257113 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7](C(O)=O)[N:8]=[CH:9]2)=[CH:4][CH:3]=1.C([N:17](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>Cl>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH2:17])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 178423957-Chloroisoquinoline-3-carboxylic acid

Product 1

HCID 233211687-Chloroisoquinolin-3-amineYield 20%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

7-Chloroisoquinoline-3-carboxylic acid (3.1 g, 14 mmol) was dissolved in 6 N HCl (50 mL), and the mixture was heated under reflux for 4 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure. The residue was dissolved in tert-butanol (100 mL), and triethylamine (2.8 g, 28 mmol) and diphenylphosphoryl azide (5.6 mL, 26 mmol) were added. The mixture was heated under reflux overnight. After cooled to room temperature, the solvent was distilled off under reduced pressure. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1) and afforded the title compound (500 mg, 20% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): 8.62 (s, 1H), 7.66 (d, J=9 Hz, 1H), 6.86 (d, J=2.4, 1H), 6.75 (dd, J=2.4 and 9 Hz, 1H), 6.52 (s, 1H), 5.83 (s, 1H), 3.83 (s, 3H); MS: m/z 174.1 (M+H+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. distillationthe solvent was distilled off under reduced pressure
  4. dissolutionThe residue was dissolved in tert-butanol (100 mL)
  5. temperatureThe mixture was heated
  6. temperatureunder reflux overnight
  7. temperatureAfter cooled to room temperature
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1)

Sources & evidence

ORD record
ord-e6774d745ce44aa89d548611dbfc7f48
Source dataset
uspto-grants-2013_06
Patent number
US08461339B2

Reaction notes

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