# US 2024/0199533 A1 · Novel synthesis of salcaprozic acid by amide formation

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- Number: US 2024/0199533 A1
- Document ID: US20240199533A1
- Status: Published application
- Kind: A1
- Application number: 18/274,614
- Filed: 2022-01-28
- Published: 2024-06-20
- Earliest claimed: 2021-01-29
- Applicants: Novo Nordisk A/S
- Inventors: Niels Krogsgaard-Larsen; Michael Raunkjaer; Christian Walter Risinger; Rolf Hejle Taaning; Vitaly Komnatnyy
- Web page: https://patentgrep.com/patent/US20240199533A1

## CPC

- C07C 231/02: from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to a chemical process for the synthesis of the compound 8-[(2-hydroxybenzoyl)amino]octanoic acid or a derivative thereof useful in the process of making sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC), a delivery agent used in solid pharmaceutical compositions. The invention provides an efficient synthesis using less hazardous chemicals and/or a reproducible process that is easier to handle on production scale.

## Claims

### Claim 1

A method for producing a compound of formula (I),
wherein R1 is selected from hydrogen, C1-C6-alkyl, phenyl, benzyl, Mg2+, Ca2+, Li+, Na+ and K+,
comprising a step of reacting a compound of formula (II),
wherein R2 is selected from hydrogen, C1-C6-alkyl, phenyl, benzyl, Mg2+, Ca2+, Li+, Na+ and K+,
and a compound of formula (III),
wherein X is selected from O-alkyl, O-phenyl, O-benzyl and N-hydroxysuccimide (NHS).

### Claim 2 (depends on 1)

The method according to claim 1, wherein R1 is hydrogen or K+.

### Claim 3 (depends on 1)

The method according to claim 1, wherein R2 is hydrogen or K+.

### Claim 4 (depends on 1)

The method according to claim 1, wherein X is O-alkyl.

### Claim 5 (depends on 4)

The method according to claim 4, wherein X is selected from O-methyl or O-ethyl.

### Claim 6 (depends on 1)

The method according to claim 1 for producing a compound of formula (I-a),
comprising the step of reacting a compound of formula (II-a),
and the compound of formula (III-a),

### Claim 7 (depends on 1)

The method according to claim 1, wherein the compound of formula (I) is potassium 8-[(2-hydroxybenzoyl)amino]octanoate of formula (I-b),

### Claim 8

A method for producing a compound of formula (I-a),
comprising the steps of
a) reacting the compound of formula (II-a),
and the compound of formula (III-a),
obtaining the compound of formula (I-b),
as an intermediate, and
b) obtaining the compound of formula (I-a) by precipitation.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the method is performed in batch mode.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the method is performed as a continuous process.

### Claim 11 (depends on 1)

A method for producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC), comprising a step of producing a compound of formula (I) [(2-hydroxybenzoyl)amino]octanoic acid, according to claim 1.

### Claim 12 (depends on 1)

A method for producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC), comprising the steps of
a) producing a compound of formula (I) 8-[(2-hydroxybenzoyl)amino]octanoic acid, according to claim 1, and
b) producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC), using the compound of formula (I) obtained in a).

### Claim 13 (depends on 1)

A method for producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC), comprising the steps of
a) producing a compound of formula (I) 8-[(2-hydroxybenzoyl)amino]octanoic acid, according to claim 1,
b) mixing a compound of formula (I) obtained in a) with 2-propanol and aqueous sodium hydroxide, and
c) precipitating sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC) from the mixture of b).

### Claim 14 (depends on 1)

A method of producing a solid pharmaceutical composition, comprising the steps of
a) producing a compound of formula (I) 8-[(2-hydroxybenzoyl)amino]octanoic acid, according to claim 1,
b) producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC) using the compound of formula (I) obtained in a), and
c) preparing said solid pharmaceutical compositions using the sodium N-(8[2-hydroxybenzoyl]-amino)caprylate obtained in step b).

### Claim 15 (depends on 11)

A method of producing a solid pharmaceutical composition comprising sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC), comprising the steps of
a) producing sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC) according to claim 11, and
b) preparing said solid pharmaceutical compositions using the sodium N-(8[2-hydroxybenzoyl]-amino)caprylate (SNAC) obtained in step a).

### Claim 16 (depends on 2)

The method according to claim 2, wherein R2 is hydrogen or K+.

### Claim 17 (depends on 5)

The method according to claim 5, wherein X is O-methyl.

### Claim 18 (depends on 13)

The method according to claim 13, wherein the method is performed in batch mode.

### Claim 19 (depends on 13)

The method according to claim 13, wherein the method is performed as a continuous process.