Hydrochloric Acid → 1H-Pyrrolo(2,3-b)pyridine

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Reaction Steps

A solution of the product of step (a) (50.0 g) in tetrahydrofuran (1.0 liter) cooled to -5° C. was treated with n-butyllithium (210 ml, 0.53 mol, 2.5M, 2.2 eq) at such a rate as to maintain the temperature ≤+2° C. On complete addition (45 minutes) the resulting deep red mixture was aged at 0° C. for 1 hour. The vigorously stirred solution was then treated with anhydrous dimethylformamide (24.2 ml, 0.3 mol, 1.3 eq.) in one portion. The resulting yellow slurry was stirred at 10° C. to room temperature over 30 minutes and then treated, rapidly, with 5.5M hydrochloric acid (250 ml). The ensuing exotherm took the temperature to 45° C. The mixture was heated at 45° to 50° C. for 1 hour, cooled to room temperature and the phases separated. The organic phase was extracted with 2M hydrochloric acid (250 ml) and the combined aqueous phases cooled to 0° C. Isopropyl acetate (250 ml) was added and the stirred mixture treated with 5M sodium hydroxide solution (250 ml) at such a rate as to maintain the temperature at ≤20° C. The mixture was stirred for 5 minutes, allowed to settle and the phases separated. The aqueous phase was extracted with isopropyl acetate (250 ml). The combined isopropyl acetate phases were washed with saturated brine (250 ml) and the isopropyl acetate solution assayed for 7-azaindole: HPLC assay=94.7%w/w (method 2) yield=26.8 g.

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