6-Aminoisoquinolin-1-ol synthesis

Yield:216099-46-6 90%

Reaction Conditions:

Stage #1:6-bromo-2H-isoquinoline-1-one with Benzophenone imine;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl;sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ in toluene at 105; for 72 h;
Stage #2: with methanol;hydroxylamine hydrochloride;sodium acetate in toluene at 20; for 72 h;

Steps:

130.130A
To toluene (4 mL) was added 6-bromoisoquinolin-l(2H)-one (0.5 g, 2.232 mmol), diphenylmethanimine (0.447 mL, 2.68 mmol), BINAP (0.973 g, 1.562 mmol), and sodium t-butoxide (0.643 g, 6.69 mmol). The slurry was degassed for 10 min with N2 followed by the addition of rø(dibenzylideneacetone) dipalladium(O) (0.101 g, 0.111 mmol) and the reaction mixture was heated to 105⁰C for 72 h. Hydroxylamine hydrochloride (0.279 g, 4.02 mmol), sodium acetate (0.439 g, 5.36 mmol) and MeOH (20 mL) were subsequently added and the reaction mixture was stirred at rt for 72 h, concentrated and purified by silica gel chromatography (DCM and 0-10%MeOH as eluents) to afford 130A (0.32g, 90%) as a tan powder. LCMS m/z 161.1 [M + H]⁺.

References:

BRISTOL-MYERS SQUIBB COMPANY WO2008/157162, 2008, A1 Location in patent:Page/Page column 199

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