# US 10,370,359 B2 · Process for the preparation of crystalline dexlansoprazole

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- Number: US 10,370,359 B2
- Document ID: US10370359B2
- Status: Granted
- Kind: B2
- Application number: 15/969,383
- Filed: 2018-05-02
- Published: 2018-11-15
- Granted: 2019-08-06
- Earliest claimed: 2017-05-09
- Assignees: Dipharma Francis S.R.L.
- Applicants: DIPHARMA FRANCIS S.r.l.
- Inventors: Alessandro Restelli; Alessio Bove; Gabriele Razzetti
- Web page: https://patentgrep.com/patent/US10370359B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention relates to a process for the preparation of anhydrous crystalline 2-(R)-[(3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methyl)sulfinyl]-1H-benzimidazole (dexlansoprazole).

## Claims

### Claim 1

A process for the preparation of crystalline anhydrous dexlansoprazole, characterized by an XRPD pattern having peaks at 7.5, 11.4, 13.1, 13.5, 15.1, 15.4, 17.3, 20.0, 21.7, 22.5, 24.0, 26.1, 27.3 and 28.6±0.2° in 2θ, comprising:
a) dispersing dexlansoprazole in one or more C5-C9 alkanes or a mixture comprising one or more C5-C9 alkanes and one or more C1-C6 alcohols at a temperature of up to 50° C. to produce a dispersion;
b) cooling the dispersion to form a precipitate of crystalline anhydrous dexlansoprazole or
azeotropically distilling the dispersion at a temperature of up to 50° C. or
azeotropically distilling the dispersion at a temperature of up to 50° C. and cooling the dispersion to form a precipitate of crystalline anhydrous dexlansoprazole;
c) recovering the solid; and
wherein the process does not comprise the step of complete dissolution of dexlansoprazole in an alcoholic solvent.

### Claim 2 (depends on 1)

The process according to claim 1, wherein the process does not comprise a step wherein an anti-solvent or mixture of anti-solvents is added to the dispersion.

### Claim 3 (depends on 1)

The process according to claim 1, wherein the dexlansoprazole dispersed in step a) is amorphous or crystalline hydrate dexlansoprazole.

### Claim 4 (depends on 3)

The process according to claim 3, wherein the crystalline hydrate dexlansoprazole is selected from the group consisting of dexlansoprazole sesquihydrate and crystalline dexlansoprazole monohydrate hemisolvated with ethanol (form D).

### Claim 5 (depends on 1)

The process according to claim 1, wherein the C5-C9 alkane is selected from the group consisting of hexane and heptane and wherein the C1-C6 alcohol is selected from the group consisting of methanol, ethanol, isopropanol, 1-butanol and 2-butanol.

### Claim 6 (depends on 1)

The process according to claim 1, wherein the ratio between the C1-C6 alcohol and the C5-C9 alkane in the mixture is 1:1 (volume:volume, v:v) or lower.

### Claim 7 (depends on 6)

The process according to claim 6, wherein the ratio between the C1-C6 alcohol and the C5-C9 alkane in the mixture is between 1:10 (v:v) and 1:1 (v:v).

### Claim 8 (depends on 7)

The process according to claim 7, wherein the ratio between the C1-C6 alcohol and the C5-C9 alkane in the mixture is 2:11 (v:v).

### Claim 9 (depends on 7)

The process according to claim 7, wherein the ratio between the C1-C6 alcohol and the C5-C9 alkane in the mixture is 2:9 (v:v).

### Claim 10 (depends on 7)

The process according to claim 7, wherein the ratio between the C1-C6 alcohol and the C5-C9 alkane in the mixture is 1:6 (v:v).

### Claim 11 (depends on 1)

The process according to claim 1, wherein the concentration of dexlansoprazole in the dispersion is between 5% and 50%.

### Claim 12 (depends on 1)

The process according to claim 1, wherein the concentration of dexlansoprazole in the dispersion is between 10% and 40%.

### Claim 13 (depends on 1)

The process according to claim 1, wherein the dispersing of dexlansoprazole in the solvent is carried out at a temperature of up to about 40° C.

### Claim 14 (depends on 1)

The process according to claim 1, wherein the cooling of the dispersion to form a precipitate of crystalline anhydrous dexlansoprazole is carried out at a temperature lower than or equal to about 20° C.

### Claim 15 (depends on 14)

The process according to claim 14, wherein, before the cooling, the dispersion is subjected to azeotropic distillation.