Ammonia → (R)-4-Hydroxy-7-(1-hydroxy-2-(2-(6-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)hexylthio)ethylamino)ethyl)benzo[d]thiazol-2(3H)-one formate

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Reaction Steps

To a solution (R)-tert-butyl 2-(6-(1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)hexylthio)ethyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)carbamate (example 101, step g) (0.093 g) in DMF (3 mL) was added triethylamine (0.062 mL) and 2-isopropyl-thiazole-4-carboxylic acid (0.025 g) followed by O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.079 g). The resultant mixture was stirred at RT for 4 h then 4 drops of ‘880’ aqueous ammonia were added and the mixture was stirred for 15 min. Brine and ethyl acetate were added to the solution and the phases were separated, then the organic phase was extracted with ethyl acetate (×2). The combined organic phase was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in DCM (2 mL) then trifluoroacetic acid (1 mL) was added. The solution was left to stand at RT for 40 min then toluene (20 mL) was added and the mixture was concentrated in vacuo. A further amount of toluene was added and the mixture concentrated again before the material was azeotroped with acetonitrile. Purification was by preparative HPLC (Phenomenex Gemini®, Gradient: 10-40% acetonitrile in 0.1% aqueous formic acid). The fractions containing product were combined and freeze dried to give the titled compound as a colourless solid. Yield 0.016 g.

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