# US 9,006,436 B2 · Preparation method of intermediate of sitagliptin

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,006,436 B2
- Document ID: US9006436B2
- Status: Granted
- Kind: B2
- Application number: 13/977,919
- Filed: 2012-01-18
- Published: 2014-01-02
- Granted: 2015-04-14
- Earliest claimed: 2011-01-20
- Assignees: St Pharm Co., Ltd.
- Applicants: Geun Gho Lim; Sun Ki Chang; Chang Ho Byeon
- Inventors: Geun Gho Lim; Sun Ki Chang; Chang Ho Byeon
- Web page: https://patentgrep.com/patent/US9006436B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides a method which enables the simple, economical and high-yield production which is a key intermediate of antidiabetic drug Januvia.

## Claims

### Claim 1

A method for preparing a compound of Formula 2:
wherein R is t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethyloxycarbonyl (Fmoc), acetyl or benzoyl, comprising:
reacting a compound of Formula 3:
wherein R is t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethyloxycarbonyl (Fmoc), acetyl or benzoyl, with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine or a salt thereof in an organic solvent in the presence of 2-chloro-4,6-dimethoxy-1,3,5-triazine and a tertiary organic amine to produce a compound of Formula 2.

### Claim 2 (depends on 1)

The method of claim 1, wherein R in Formula 2 and Formula 3 is Boc or Cbz.

### Claim 3 (depends on 1)

The method of claim 1, wherein the tertiary organic amine is N-methylmorpholine, pyridine, triethylamine, trimethylamine, triisopropylamine or quinoline.

### Claim 4 (depends on 3)

The method of claim 3, wherein the tertiary organic amine is N-methylmorpholine.

### Claim 5 (depends on 1)

The of claim 1, wherein the organic solvent is selected from the group consisting of tetrahydrofuran, N,N-dimethylformamide, toluene and dichloromethane.

### Claim 6 (depends on 1)

The method of claim 1, wherein the reaction is carried out at a temperature of 0 to 30° C.

### Claim 7 (depends on 1)

The method of claim 1, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 8 (depends on 2)

The method of claim 2, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 9 (depends on 3)

The method of claim 3, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 10 (depends on 4)

The method of claim 4, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 11 (depends on 5)

The method of claim 5, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 12 (depends on 6)

The method of claim 6, further comprising adding ethyl acetate and isopropyl alcohol to form a crystallized compound of Formula 2.

### Claim 13 (depends on 1)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 1; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.

### Claim 14 (depends on 2)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 2; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.

### Claim 15 (depends on 3)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 3; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.

### Claim 16 (depends on 4)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 4; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.

### Claim 17 (depends on 5)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 5; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.

### Claim 18 (depends on 6)

A method for preparing a sitagliptin phosphate monohydrate, comprising:
preparing a compound of Formula 2 according to the method of claim 6; and
treating the compound of Formula 2 to yield sitagliptin phosphate monohydrate.