Ammonia → 1,6-Naphthyridine-5,7(6H,8H)-dione

Participants

Reaction Conditions

Reaction Steps

Tetrahydrofuran (9 vol) is charged to the reactor followed by the starting material ester (1 eq) and a rinse of tetrahydrofuran (1 vol). The mixture is cooled to −2.5±7.5° C. under nitrogen atmosphere then treated with triethylamine (1.35 eq) and later ethyl chloroformate (1.25 eq). The reaction is stirred for 1 h at −2.5±7.5° C. then sampled. On receipt of a successful result the reaction is carefully treated with aq. ammonia, stirred, then water is added. Dilute HCl is added at <5° C. to adjust the pH to 6.5-7.5. The mixture is distilled under vacuum at <40° C. to 12-14 volumes and cooled to 7.5±2.5° C. The suspension is stirred ˜1 h at 7.5±2.5° C. then filtered. The solid is washed with water (1 vol) then offloaded and dried under vacuum (NLT 650 mm of Hg) at 52.5±2.5° C. for 12.0 h.

Provenance & Evidence