Practical and Efficient Route to Dolutegravir Sodium via One-Pot Synthesis of Key Intermediate with Controlled Formation of Impurities

An efficient, cost effective and commercially viable synthesis of dolutegravir sodium has been developed from commercially available methyl 4-methoxy-3-oxobutanote through 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid as the key intermediate. The key features of the synthesis are lower number of synthetic steps and the use of eco-friendly and inexpensive reagents. The process has been demonstrated to meet ICH requirements on scaling up.