Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form

摘要

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —OR_i or —NR_2aR_2b; R₃ is hydrogen or substituted or unsubstituted heteroalicyclyl, R₄ is substituted or unsubstituted aralkyl; X is —OR₂₂ or —NR₂₃R₂₄; (wherein R₂₂ is hydrogen or substituted or unsubstituted C_1-6alkyl and one of R₂₃ and R₂₄ is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R₂₁ is —OCH₂CH(CH₃)₂ or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.;