Ammonium Hydroxide → 8-[3-(2-Methyl-pyrrolidin-1-yl)-propoxy]-4,4a,5,6-tetrahydro-2H-benzo[h]cinnolin-3-one

Participants

Reaction Steps

In a 250 mL round bottom flask, 6-[3-((R)-2-Methyl-pyrrolidin-1-yl)-propoxy]-3,4-dihydro-2H-naphthalen-1-one (3.0 g, 9.3 mmol), and glyoxylic acid monohydrate (1.28 g, 13.9 mmol), in acetic acid (60 mL) was heated to reflux 3 h. The reaction was cooled and zinc dust (1.21 g, 18.5 mmol) was added and the reaction was heated to reflux 14 h. The reaction was cooled and diluted with water (120 mL). The mixture was basified to pH 8 with NH4OH and then hydrazine monohydrate (0.93 mL, 18.5 mmol) was added. The reaction was heated to reflux 2 h. The reaction was cooled and re-basified with NaHCO3, then extracted with methylene chloride three times. The organics were dried over MgSO4, then ethereal HCL was added. The solvents were removed under vacuum and the product was crystallized with MeOH/ether to produce 1.16 g (33%). Mp 193-195° C. MS m/z 342 (M+H).

Provenance & Evidence