Sulfuric Acid → 7-Chloroisoquinolin-3-amine

HRID 1876017Notes

Reaction equation

HRID 1876017 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][NH:6][C:7](=[NH:15])[CH:8](OCC)OCC.S(=O)(=O)(O)O.[OH-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:16]([CH:8]=[C:7]([NH2:15])[N:6]=[CH:5]2)=[CH:17][CH:18]=1.[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:4]2[C:3]=1[CH:8]=[C:7]([NH2:15])[N:6]=[CH:5]2

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 178471671HCID 178471671, compound

Product 2

HCID 233211687-Chloroisoquinolin-3-amineHCID 534184815-Chloroisoquinolin-3-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a flask was placed N-(3-chlorobenzyl)-2,2-diethoxyacetimidamide (1.9 g, 7.02 mmol) and sulfuric acid (14 mL, 263 mmol). This was stirred at room temperature for 24 hours. The reaction was then neutralized to pH 9 using 10 N NaOH. The resulting precipitate was dissolved in dichloromethane and the water layer was washed with dichloromethane. The organic layers were combined and concentrated to give the above regioisomers (1.1 grams, 6.1 mmol, 88%) in a 2:1 ratio of 7-chloroisoquinolin-3-amine to 5-chloroisoquinolin-3-amine. This regioisomer mixture is carried on without further separation. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.89 (s, 1H) 8.81 (s, 2H) 7.90 (d, J=2.26 Hz, 2H) 7.82 (d, J=8.28 Hz, 1H) 7.65 (dd, J=7.28, 1.00 Hz, 1H) 7.58 (d, J=9.03 Hz, 2H) 7.44 (dd, J=9.03, 2.26 Hz, 2H) 7.07-7.19 (m, 1H) 6.83 (s, 1H) 6.64 (s, 2H) 6.28 (s, 2H) 6.05 (s, 4H) LC/MS R.T=0.955 mins, [M+H]=181.03

Workup

  1. customIn a flask was placed
  2. washthe water layer was washed with dichloromethane
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-0c742d475b494722a1d315f6addef246
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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