Patent ID: 8129523
Filing Date: 2012-03-06
Classification: C07D,C07F

Abstract:
1. A method of preparing 5-(4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-methyl-pyrrole-2-carbonitrile comprising: (a) reacting 1-methyl-pyrrole-2-carbonitrile, lithium di-isopropylamide and tri-isopropylborate; (b) reacting the product of step (a) with 6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, potassium carbonate, and a soluble palladium (0) catalyst; (c) washing the 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-methyl-pyrrole-2-carbonitrile with water and THF; (d) adjusting the pH of the product of step (c) to 4 to 5; (e) adding L-cysteine to the product of step (d); (f) removing excess cysteine; (g) exchanging the THF for toluene; (h) precipitating the product of step (g); and (i) drying the purified 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-methyl-pyrrole-2-carbonitrile; and (j) reacting said purified 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-methyl-pyrrole-2-carbonitrile and Lawesson's reagent.