# US 10,246,460 B2 · Synthesis of trans-8-chloro-5-methyl-1-[4-(pyridin-2-yloxy)-cyclohexyl]-5,6-dihydro-4H-2,3,5,10B-tetraaza-benzo[E]azulene and crytalline forms thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,246,460 B2
- Document ID: US10246460B2
- Status: Granted
- Kind: B2
- Application number: 15/172,542
- Filed: 2016-06-03
- Published: 2016-09-29
- Granted: 2019-04-02
- Earliest claimed: 2013-12-05
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Benno Rothenhaeusler; Rene Trussardi; Fabienne Hoffmann-Emery; Urs Schwitter; Jean-Michel Adam; Olaf Grassmann; Thomas Hartung; Frederic Ran; Ralph Diodone; Christophe Pfleger; Bjorn Bartels
- Web page: https://patentgrep.com/patent/US10246460B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 25/00: Drugs for disorders of the nervous system
- C07D 243/14: 1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention provides processes to manufacture substituted 1-[4-(Pyridin-2-yloxy)-cyclohexyl]-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes. Also disclosed are compounds useful as intermediates in the methods of the invention.

## Claims

### Claim 1

A process to synthesize compound formula I, comprising reacting compound formula III with compound formula VI

### Claim 2 (depends on 1)

The process according to claim 1, further comprising reacting compound formula XI to form compound formula III:

### Claim 3 (depends on 2)

The process according to claim 2 further comprising reacting compound formula X to form compound of formula IX; reacting compound formula IX to form compound of formula VIII; reacting compound formula VIII to form compound of formula VII; and reacting compound formula VII to form compound of formula XI or a pharmaceutically acceptable salt thereof via the following series of steps:

### Claim 4 (depends on 2)

The process according to claim 2 further comprising reacting compound formula XV to form compound formula XIV; reacting compound formula XIV to form compound formula XIII; reacting compound formula XIII to form compound formula XII; and reacting compound formula XII to form compound formula XI or a pharmaceutically acceptable salt thereof via the following series of steps:

### Claim 5 (depends on 2)

The process according to claim 2 further comprising reacting compound formula XXVI to form compound formula XII and reacting compound formula XII to form compound formula XI or a pharmaceutically acceptable salt thereof via the series of following steps

### Claim 6 (depends on 1)

The process according to claim 1, whereby compound formula INT is formed as intermediate from the reaction of compound formula III and compound formula VI according to the following steps, and wherein compound formula INT is reacted to form compound formula I: