Methanol → Nevirapine

Participants

Reaction Conditions

Reaction Steps

A reaction flask equipped with a magnetic stirrer, temperature controller thermodouple, addition funnel and condenser with an oil bubbler for exclusion of ambient air was inerted with nitrogen and charged with 3.02 g (0.010 mol) of N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide from Example 4 and 30 ml of anhydrous THF. A 40% solution of sodium hexamethyldisilazane in THF (12.7 ml, 0.025 mol) was added dropwise maintaining the temperature of the reaction mixture at no more than 30° C. When the addition of the NaHMDS solution was completed, the reaction mixture was heated to reflux temperature (about 63-66° C.). When the reaction was completed (HPLC analysis), the mixture was cooled to ambient temperature. The reaction mixture was treated with 1.55 g (0.050 mol) of methanol and 0.45 g of water (0.025 mol). The mixture was concentrated on a rotary evaporator at 25-30 in. Hg with a 50-60° water bath temperature. The residual product weighing 4.44 g was triturated with 50 ml of water and the pH 10-12 solution was acidified to pH 3 by adding 10% HCl solution. The solid product was collected by filtration and the filter cake rinsed three times with 10 ml portions of water. The filter cake was dried in a vacuum oven at 50-60° C. to obtain nevirapine.

Provenance & Evidence