# US 10,479,769 B2 · Processes for the preparation of eluxadoline

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- Number: US 10,479,769 B2
- Document ID: US10479769B2
- Status: Granted
- Kind: B2
- Application number: 16/335,013
- Filed: 2017-09-20
- Published: 2019-08-15
- Granted: 2019-11-19
- Earliest claimed: 2016-09-20
- Assignees: Sun Pharmaceutical Industries Limited
- Applicants: Sun Pharmaceutical Industries Limited
- Inventors: Murad Ismail Inamdar; Sriram Hari Mohan; Ketan Vithalbhai Hirpara
- Web page: https://patentgrep.com/patent/US10479769B2

## CPC

- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to processes for the preparation of eluxadoline. The present invention also provides a compound of Formula V, a process for its preparation, and its use for the preparation of eluxadoline.

## Claims

### Claim 1

A process for the preparation of eluxadoline of Formula I,
comprising
a) deprotecting a compound of Formula II
wherein PG is a nitrogen protecting group;
in the presence of a deprotecting agent to obtain a compound of Formula III;
b) reductive amination of the compound of Formula III with a compound of Formula IV
wherein R is hydrogen or C1-6 alkyl;
followed by the treatment with an acid to obtain a compound of Formula V
wherein R is hydrogen or C1-6 alkyl; and
c) converting the compound of Formula V to eluxadoline of Formula I.

### Claim 2

A compound of Formula V,
wherein the salt is selected from the group consisting of citrate, acetate, fumarate, lactate, maleate, malate, tartrate, benzoate, mesylate, oxalate, tosylate, and succinate; and
wherein R is hydrogen or C1-6 alkyl.

### Claim 3

A compound of Formula Va,
wherein the salt is selected from the group consisting of citrate, acetate, fumarate, lactate, maleate, malate, tartrate, benzoate, mesylate, oxalate, tosylate, and succinate.

### Claim 4 (depends on 1)

The process according to claim 1, wherein the acid is selected from the group consisting of citric acid, acetic acid, fumaric acid, lactic acid, maleic acid, malic acid, tartaric acid, benzoic acid, methanesulfonic acid, oxalic acid, p-toluenesulfonic acid, and succinic acid.

### Claim 5 (depends on 1)

The process according to claim 1, wherein the reductive amination is carried out in the presence of a reducing agent in a solvent.

### Claim 6 (depends on 5)

The process according to claim 5, wherein the reducing agent is selected from the group consisting of sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, lithium borohydride, potassium borohydride, Raney Nickel, and Palladium on carbon (Pd/C).

### Claim 7 (depends on 4)

The process according to claim 4, wherein the solvent is selected from the group consisting of alcohols, nitriles, halogenated hydrocarbons, ethers, water, and mixtures thereof.

### Claim 8 (depends on 1)

The process according to claim 1, wherein the compound of Formula V is converted into Eluxadoline of Formula I by treating the compound of Formula V with a base in a solvent to obtain a compound of Formula VI,
wherein R is hydrogen or C1-6 alkyl; and
converting the compound of Formula VI into Eluxadoline of Formula I.

### Claim 9 (depends on 7)

The process according to claim 7, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, sodium bicarbonate, potassium bicarbonate, and cesium hydroxide.

### Claim 10 (depends on 7)

The process according to claim 7, wherein the solvent is selected from the group consisting of alcohols, nitriles, halogenated hydrocarbons, ethers, water, and mixtures thereof.