# US 7,745,471 B2 · Derivatives of 1,2-benzisoxazole-3-methane sulfonic acid as novel intermediates for the synthesis of zonisamide

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- Number: US 7,745,471 B2
- Document ID: US7745471B2
- Status: Granted
- Kind: B2
- Application number: 11/153,402
- Filed: 2005-06-16
- Published: 2006-01-19
- Granted: 2010-06-29
- Earliest claimed: 2004-06-18
- Assignees: Chemagis Ltd.
- Inventors: Vladimir Naddaka; Eyal Klopfer; Shady Saeed; Oded Arad; Joseph Kaspi
- Web page: https://patentgrep.com/patent/US7745471B2

## CPC

- C07D 261/20: condensed with carbocyclic rings or ring systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Derivatives of 1,2-benzisoxazole-3-methanesulfonic acid, which are non-hygroscopic and non-hydrated and their use as intermediates from the preparation of zonisamide are disclosed. Further disclosed are processes of preparing zonisamide from these 1,2-benzisoxazole-3-methanesulfonic acid derivatives, processes of preparing exemplary 1,2-benzisoxazole-3-methanesulfonic acid derivatives and crystalline forms of exemplary 2-benzisoxazole-3-methanesulfonic acid derivatives. A novel process of preparing zonisamide is also disclosed.

## Claims

### Claim 1

A 1,2-benzisoxazole-3-methanesulfonic acid ester of the formula:
wherein R is selected from alkyl, cycloalkyl, aryl, aralkyl and alkaryl.

### Claim 2

A process of preparing 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt, the process comprising; providing a first mixture containing 3-bromomethyl-1,2-benzisoxazole and a first alcohol; providing a second mixture containing ammonium sulfite and water; reacting said first mixture and said second mixture to thereby obtain a reaction mixture containing the 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt; and isolating the 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt from said reaction mixture, thereby obtaining the 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt.

### Claim 3 (depends on 2)

The process of claim 2, wherein said first alcohol is selected from the group consisting of methanol, ethanol, 1-propanol and 2-propanol.

### Claim 4 (depends on 2)

The process of claim 2, wherein said isolating is effected by: removing said first alcohol and said water from said reaction mixture, to thereby provide a residue containing the 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt; dissolving said residue in a second alcohol, to thereby provide a solution containing said 1,2-benzisoxazole-3-methanesulfonic acid ammonium salt and optionally insoluble impurities; filtering said insoluble impurities; and removing said second alcohol.

### Claim 5 (depends on 4)

The process of claim 4, wherein said second alcohol is selected from the group consisting of methanol, ethanol, 1-propanol and 2-propanol.

### Claim 6

A process for preparing zonisamide, the process comprising converting the 1,2-benzisoxazole-3-methanesulfonic acid ester of the formula:
wherein R is selected from alkyl, cycloalkyl, aryl, aralkyl and alkaryl, into zonisamide.