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

US10981871B2 · kind B2 · utility

Assignee

• ACADIA Pharmaceuticals Inc. · US

Inventors

• Marlon Carlos · Chula Vista, US
• Sagun Tandel · San Diego, US
• Roger Olsson · Bunkeflostrand, SE
• Mikael Hillgren · Örebro, SE
• Matthew J. Fleming · Zofingen, CH
• Andreas Boudier · Zürich, CH
• Beat Weber · Zofingen, CH

Key dates

• Filing date: Feb 10, 2020
• Grant date: Apr 20, 2021
• Expiry date: Feb 10, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D211/98
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

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 —ORi or —NR2aR2b; 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 C1-6alkyl 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.