# US 11,440,921 B2 · Salts, crystal forms, and production methods thereof

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- Number: US 11,440,921 B2
- Document ID: US11440921B2
- Status: Granted
- Kind: B2
- Application number: 17/006,101
- Filed: 2020-08-28
- Published: 2021-02-25
- Granted: 2022-09-13
- Earliest claimed: 2018-02-16
- Assignees: Sunovion Pharmaceuticals Inc.
- Applicants: Sunovion Pharmaceuticals Inc.
- Inventors: Andrea Bauer; Nandkumar Nivritti Bhogle; Xiaoxia Chen; Shahla Jamzad; Robert Joseph Prytko; Kostas Saranteas; Michael Joseph Sizensky; Harold Scott Wilkinson; Haitao Zhang
- Web page: https://patentgrep.com/patent/US11440921B2

## CPC

- C07D 495/04: Ortho-condensed systems
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 31/381: having five-membered rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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

Provided are salts of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine and various of crystal forms thereof, and compositions, medicaments, pharmaceutically acceptable formulations thereof, and methods of making same. In addition, provided are compounds comprising specific particle size distributions of crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine HCl and methods of making and modulating the particle size distributions.

## Claims

### Claim 1

A compound which is crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 9.6±0.2°, 14.9±0.2°, 20.5±0.2°, and 25.1±0.2°.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride is further characterized by the powder x-ray diffraction pattern further comprising a peak, in terms of 2-theta, at 20.2±0.2° and 20.8±0.2°.

### Claim 3 (depends on 1, 2)

The compound of claim 1 or 2, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride is further characterized by the powder x-ray diffraction pattern further comprising a peak, in terms of 2-theta, at two or more of 17.9±0.2°, 24.8±0.2° and 27.1±0.2°.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride is characterized by a powder x-ray diffraction pattern of FIG. 2B.

### Claim 5 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has a differential scanning calorimetry thermogram comprising a peak at 214±2° C.

### Claim 6 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has a differential scanning calorimetry thermogram of FIG. 3A.

### Claim 7 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride is characterized by monoclinic space group P21.

### Claim 8 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has unit cell dimensions: α is about 9.2 Å, b is about 11.2 Å, c is about 10.2 Å, α is about 90°, β is about 92°, and γ is about 90°, wherein the term about means within 2% of each indicated value.

### Claim 9 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has chiral purity greater than 90% (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride.

### Claim 10 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has chiral purity greater than 95% (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride.

### Claim 11 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has chemical purity greater than 95% (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride.

### Claim 12 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has chemical purity greater than 99% (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride.

### Claim 13 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has chemical purity of greater than 99.5%.

### Claim 14 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has polymorph purity of greater than 95%.

### Claim 15 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has a Raman spectrum of FIG. 4A.

### Claim 16 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride has a THz Raman spectrum of FIG. 4D.

### Claim 17 (depends on 1)

The compound of claim 1, wherein the crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride is substantially non-hygroscopic.

### Claim 18 (depends on 1, 10, 12)

A pharmaceutical composition comprising the compound of any one of claims 1, 10, 12, or 14 and one or more pharmaceutically acceptable excipients.

### Claim 19 (depends on 18)

The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of fillers, disintegrants, and lubricants.

### Claim 20 (depends on 18)

The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of mannitol, microcrystalline cellulose, sodium starch glycolate, and magnesium stearate.

### Claim 21 (depends on 18)

The pharmaceutical composition of claim 18 comprising:
(a) 10 mg to 120 mg, on a free base basis, of crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride;
(b) mannitol;
(c) microcrystalline cellulose;
(d) sodium starch glycolate; and
(e) magnesium stearate.