Procedure for preparcion of N - (5 - (4 - dimethylamino - acryloyl = - 2 - fluoro phenyl) - n-methyl acetamide and N - (2-fluoro-5 - (= - 3 - 2 - thiophene carbonyl pyrazolo (1,5-a) pyrimidine 7 - il) phenyl) - n-methyl acetamide And Compound N - (5 - acetyl - 2-fluorophenyl) - n-methyl acetamide

摘要

Process for the preparation of compound N - [5 - (4 - dimethylamino - acryloyl) Floro - phenyl - 2 -] - n-methyl acetamide of formula (1), an intermediate in the synthesis of compounds with Affinity for the Gabaa receptor, with high yield and Purity.In this procedure the N - (5 - acetyl - 2 - fluorofenii) - n-methyl acetamide formula (6) is reacted with an excess of N, n-dimethylformamide (dimetilacetal nndmf - DMA).It also provides a method for preparing the product with Affinity Gabaa N - {2-fluoro-5 - [3 - (Thiophene) - 2 - carbonyl pyrazolo [1,5-a] pyrimidine 7 - il] phenyl) - n-methylacetamide formula (2), which comprises the steps of (a) methylation of N - (5 - acetyl - 2-fluorophenyl) - acetamide formula (4) With a Methyl sulfonate, b) reaction of the compound of formula (6) resulting nndmf - DMAAnd (c) reaction of the compound of formula (1) with (resulting 5-amino - 1h-pyrazol-4-yl) thiophene - 2 - il - methanone formula (3) in glacial acetic acid. Also refers to the intermediate of formula (6) is the N - (5 - acetyl - 2-fluorophenyl) - n-methyl acetamide.Claim 1: procedure for the preparation of N - [5 - (4 - dimethylamino - acryloyl) - 2 - fluoro phenyl n-methyl acetamide, wherein is formula (1) comprising the reaction of a compound of formula (6) with excess n, n-dimethylformamide (nndmf dimetilacetal - DMA) According to a proportion 1.5 - 2.5 mol per mol of nndmf - DMA Compound of formula (6) to reflux.Followed by addition of an Aromatic apolar Solvent selected from the group consisting of toluene, o-xylene, m-xylene and p-xylene and ETHYLBENZENE, Styrene, Cumene, and their mixtures, at a temperature between 70 and 90sc and then a non-polar aliphatic Solvent selected from the group with Consistent in n-hexane, n-heptane.N-octane, 2,5-dimethylhexane, cyclohexane, methylcyclohexane, and their mixtures at the same temperature.