HCID 178471677, compound → 6-Methoxyisoquinolin-3-amine

HRID 1257115Notes

Reaction equation

HRID 1257115 reaction equation
C(O[CH:4](OCC)[C:5](=[NH:16])[NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)C>S(=O)(=O)(O)O>[CH3:15][O:14][C:11]1[CH:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[CH:7]=[N:6][C:5]([NH2:16])=[CH:4]2

Participants

3

Reactant 1

HCID 178471677HCID 178471677, compound

Product 1

HCID 233211576-Methoxyisoquinolin-3-amineYield 2.9%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

The crude 2,2-diethoxy-N-(4-methoxybenzyl)acetimidamide (23 g) was added dropwise to conc. sulfuric acid (200 mL) at 20˜25° C. with stirring. The mixture was stirred at room temperature for 48 hours and then quenched with ice (1 Kg). 12 N NaOH solution (400 mL) was added to give a final pH of 9˜10. The resulting suspension was extracted with CH2Cl2 (5×2 L). The organic layers were combined, washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1) and afforded the title compound (430 mg, 2.9% yield based on p-methoxybenzylamine) 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 175.1 (M+H+).

Workup

  1. stirringThe mixture was stirred at room temperature for 48 hours
  2. customquenched with ice (1 Kg)
  3. addition12 N NaOH solution (400 mL) was added
  4. customto give a final pH of 9˜10
  5. extractionThe resulting suspension was extracted with CH2Cl2 (5×2 L)
  6. washwashed with brine (500 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1)

Sources & evidence

ORD record
ord-d43cf9977a8d45638deeec8771c003aa
Source dataset
uspto-grants-2013_06
Patent number
US08461339B2

Reaction notes

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