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

A method of preparing pimavanserin (N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide) or a salt thereof, the method comprising:

• contacting an intermediate according to Formula (A),
• or a salt thereof, with an intermediate according to Formula (B),
• or a salt thereof, to produce pimavanserin or a salt thereof wherein
• Y is —OR1 or —NR2a, R2b;
• R1, R2a, R2b, independently of each other are selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, and substituted or unsubstituted aryl;
• or
• R2a and R2b taken together with the nitrogen to which they are attached form a substituted or unsubstituted heteroalicyclyl, substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl;
• R3 is hydrogen or substituted or unsubstituted heteroalicyclyl,
• R4 is substituted or unsubstituted aralkyl;
• X is —OR22 or —NR23R24;
• R21 is —OCH2CH(CH3)2 or F;
• R22 is hydrogen or substituted or unsubstituted C1-6 alkyl;
• and
• one of R23 and R24 is hydrogen and the other of R23 and R24 is N-methylpiperidin-4-yl, or both R23 and R24 are hydrogen.