Ammonium Hydroxide → HCID 59312597, compound

Participants

Reaction Steps

Concentrated ammonium hydroxide (0.15 ml, 1.079 mmol) was added to a stirred solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-[2-(ethoxycarbonyl)-4-pyridinyl]-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 171, 38.1, 0.042 mmol) in 1,4-dioxane (0.42 ml). A white precipitate formed about a minute or two after the addition of ammonium hydroxide. The reaction mixture was stirred at room temperature. After 20 hours, additional 1,4-dioxane (0.15 ml) and concentrated ammonium hydroxide (0.05 ml, 0.360 mmol) were added to the reaction mixture. After 26 hours, the reaction mixture had become a colorless solution. After 44 hours, LCMS and 1H NMR showed the reaction to be complete. The reaction mixture was evaporated under reduced pressure to give a colorless residue. The residue was dissolved in methanol and purified using a single HPLC run on a 30×150 mm Sunfire Prep C18 OBD 10 μm column by eluting with acetonitrile/water+0.1% TFA. The total flow rate was 20 ml/min and the HPLC method employed a 17 minute 20%-100% acetonitrile/water gradient followed by a 2 minute acetonitrile flush. The product fractions were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from acetonitrile and water to give the title compound (29.9 mg) as a white solid.

Provenance & Evidence