Sulfuric Acid → 5,6-Dichloroisoquinolin-3-amine

Participants

Reaction Conditions

Reaction Steps

To sulfuric acid (4 mL, 75 mmol) was added N-(3,4-dichlorobenzyl)-2,2-diethoxyacetimidamide (2 g, 6.6 mmol) at room temperature. The reaction was heated to 40° C. for 49 hours. TLC and LC/MS indicated the presence of product. The reaction was cooled to room temperature and quenched with aq. NaOH (˜15 M) until the reaction mixture was ˜pH 7. The crude product was extracted with ethyl acetate (2×50 mL) and the organics were dried with MgSO4, filtered, and concentrated in vacuo to yield the product. The crude product was purified by chromatography (Biotage: 100% ethyl acetate to [90/10% ethyl acetate/MeOH]) to yield approximately a 1:1 mixture of regioisomers 6,7-dichloroisoquinolin-1-amine and 5,6-dichloroisoquinolin-3-amine (1.2 g, 5.64 mmol, 86.0% yield) as a dark yellow powder. The regioisomers were carried on without separation. 1H NMR: 1H NMR (500 MHz, DMSO-D6) δ ppm 8.90 (s, 1H), 8.83 (s, 1H), 8.12 (s, 1H), 7.89 (s, 1H), 7.84 (d, J=8.54 Hz, 1H), 7.28 (d, J=8.85 Hz, 1H), 6.83 (s, 1H), 6.58 (s, 1H), 6.48 (s, 2H), 6.25 (s, 2H). MS (LC/MS) R.T.=1.59; [M+H]+=213.0.

Provenance & Evidence