5-Bromo-6-methoxyisoquinoline synthesis

Yield:366445-82-1 71%

Reaction Conditions:

Stage #1: 6-methoxyisoquinolinewith sulfuric acid at 0;
Stage #2: with N-Bromosuccinimide at -25 - -18; for 5 h;
Stage #3: with ammonia in water; pH=9;

Steps:

1.D

6-Methoxyisoquinoline 16 (5.32 g, 33.4 mmol) was slowly added at 0°C to cone. H₂SO₄ (33.5 mL). The mixture was cooled to -25°C and NBS (7.68 g, 43.2 mmol) was added at such a rate that the reaction temperature was kept between -25°C and -22°C. The mixture was stirred at -22°C for 2 h and at -18°C for 3 h, then poured onto crushed ice. The pH was adjusted to 9 using concentrated aqueous NH₃ and the alkaline slurry was then extracted with diethyl ether. The combined organic fractions were washed with 1 N NaOH and water, dried (Na₂SO₄), filtered and evaporated to dryness to afford 5.65 g (71%) of the target product 17: m/z = 237.8 (M+H)⁺.

References:

WO2007/14921,2007,A1 Location in patent:Page/Page column 75