Acetic Acid → (R)-4-Hydroxy-7-(1-hydroxy-2-(9-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3,3-dimethylnonylamino)ethyl)benzo[d]thiazol-2(3H)-one formate

Participants

Reaction Steps

Acetic acid (0.035 mL) was added to a stirred solution of 9-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3,3-dimethylnonanal (example 279, step f) (195 mg) and (R)-7-(2-amino-1-hydroxyethyl)-4-hydroxybenzo[d]thiazol-2(3H)-one hydrochloride (WO2007027134, example 1, step d) (161 mg) in methanol (10 mL) and after a minute sodium cyanoborohydride (51 mg) was added and the reaction mixture stirred at room temperature for 1.5 h. The mixture was concentrated and then partitioned between THF (12 mL) and a mixture of brine and saturated sodium bicarbonate solution (10:1, 12 mL). The layers were separated and the organic phase dried over sodium sulfate, filtered and evaporated. The resulting material was purified by preparative HPLC (Phenomenex Gemini®, Gradient: 5-40% acetonitrile in 0.1% aqueous formic acid). The fractions containing product were combined and freeze-dried to afford the titled compound as a white solid. Yield 0.038 g.

Provenance & Evidence