Synthesis of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and crystalline forms

• US 20060205781A1
• Filed: 05/03/2006
• Published: 09/14/2006
• Est. Priority Date: 09/27/2004
• Status: Abandoned Application

• Current Assignee: Bo-Ragnar Tolf, Carl-Magnus A. Andersson, Fritz Blatter, Jorg Berghausen, Mikkel Boas Thygesen, Nathalie Schlienger
• Original Assignee: Bo-Ragnar Tolf, Carl-Magnus A. Andersson, Fritz Blatter, Jorg Berghausen, Mikkel Boas Thygesen, Nathalie Schlienger
• Inventors: Blatter, Fritz, Thygesen, Mikkel Boas, Schlienger, Nathalie, Tolf, Bo-Ragnar, Andersson, Carl-Magnus A., Berghausen, Jorg
• Application Number:
  US11/418,341
• Publication Number:
  US 20060205781A1
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07D 211/58 attached in position 4

Abstract

Disclosed herein are methods for synthesizing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)-phenylmethyl)carbamide. Also disclosed herein is the hemi-tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)-phenylmethyl)carbamide and methods for obtaining the salt. Further disclosed are various crystalline forms of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)-phenylmethyl)carbamide and its hemi-tartrate salt including various polymorphs and solvates.

Claims

1. An isopropanolate solvate of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-(2-methylpropyloxy)phenylmethyl)carbamide tartrate.

2. A pharmaceutical composition comprising the solvate of claim 1 and a pharmaceutically acceptable carrier or diluent.

3. A t-butyl methyl ether solvate of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-(2-methylpropyloxy)phenylmethyl)carbamide tartrate.

4. A pharmaceutical composition comprising the solvate of claim 3 and a pharmaceutically acceptable carrier or diluent.

5. A tetrahydrofuran solvate of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-(2-methylpropyloxy)phenylmethyl)carbamide tartrate.

6. A pharmaceutical composition comprising the solvate of claim 5 and a pharmaceutically acceptable carrier or diluent.