PROCESS FOR THE SYNTHESIS OF GLYT-1 INHIBITORS

摘要

Process for preparation of a compound of formula (I) wherein Het is a 6-membered heteroaryl group, containing one, two or three nitrogen atoms; R¹ is (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl, NR⁴R⁵ or (C₁-C₆)-alkyl subtituted by halogen; R² is hydroxy, halogen, NO₂, CN, (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl, (C₁-C₆)-alkyl substituted by halogen, (C₁-C₆)-alkyl substituted by hydroxy, (CH₂)_o-(C₁-C₆)-alkoxy, (C₁-C₆)-alkoxy substituted by halogen, NR⁴R⁵, C(O)R⁶ or SO₂ R⁷; R³ is (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl or (C₁-C₆)-alkyl subtituted by halogen; R⁴ and R⁵ independently from each other are hydrogen or (C₁-C₆)-alkyl; R⁶ is hydrogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy or NR⁴R⁵; R⁷ is (C₁-C₆)-alkyl, (C₁-C₆)-alkyl optionally subtituted by halogen, (CH₂)_o-(C₃-C₆)-cycloalkyl, (CH₂)_o-(C₃-C₆)-alkoxy or NR⁴R⁵; n is 0, 1, 2 or 3; o is 0, 1 or 2; and pharmaceutically acceptable acid addition salts thereof, characterized in that it comprises the steps of a) reacting a compound of formula (21) with a compound of formula: R³ OH 8 to a compound of formula (11) and b) coupling the compound of formula (11) in the presence of a coupling reagent or the corresponding acid halogenide with a compound of formula (15) to obtain a compound of formula (I).