Sitagliptin phosphate monohydrate

Base Information

• Chemical Name: Sitagliptin phosphate monohydrate
• CAS No.: 654671-77-9
• Molecular Formula: C16H15F6N5O^.H3PO4^.H2O
• Molecular Weight: 523.329
• Hs Code.: 29335990
• European Community (EC) Number: 682-492-2
• UNII: TS63EW8X6F
• ChEMBL ID: CHEMBL1201174
• DSSTox Substance ID: DTXSID50904746
• NCI Thesaurus Code: C73811
• RXCUI: 621590
• Mol file: 654671-77-9.mol

Synonyms:0431, MK;4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine;Anhydrous, Sitagliptin Phosphate;Januvia;MK 0431;MK-0431;MK0431;Monohydrate, Sitagliptin Monophosphate;Monohydrate, Sitagliptin Phosphate;Monophosphate Monohydrate, Sitagliptin;Phosphate Anhydrous, Sitagliptin;Phosphate Monohydrate, Sitagliptin;Phosphate, Sitagliptin;sitagliptin;sitagliptin monophosphate monohydrate;sitagliptin phosphate;sitagliptin phosphate anhydrous;sitagliptin phosphate monohydrate

Chemical Property of Sitagliptin phosphate monohydrate

Chemical Property:

• Appearance/Colour: White or almost white crystalline powder
• Vapor Pressure: 2.59E-11mmHg at 25°C
• Boiling Point: 529.9 °C at 760 mmHg
• Flash Point: 274.3 °C
• PSA: 173.84000
• LogP: 1.66180
• Storage Temp.: 2-8°C
• Solubility.: ≥23.8 mg/mL in DMSO; insoluble in EtOH; ≥30.6 mg/mL in H2O with ultrasonic
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 15
• Rotatable Bond Count: 4
• Exact Mass: 523.10553934
• Heavy Atom Count: 34
• Complexity: 616

Purity/Quality:

99%min ^*data from raw suppliers

Sitagliptin phosphate monohydrate European Pharmacopoeia (EP) Reference Standard ^*data from reagent suppliers

Safty Information:

• Statements: 28-38-41-48-62-63
• Safety Statements: 24/25-26-28-36/37/39

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N.O.OP(=O)(O)O
• Isomeric SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N.O.OP(=O)(O)O
• Recent ClinicalTrials: Treatment of Hypoglycemia Following Gastric Bypass Surgery
• Recent EU Clinical Trials: PIONEER 12 China multi-regional clinical trial: Efficacy and safety of oral semaglutide versus sitagliptin in subjects with type 2 diabetes mellitus treated with metformin
• Recent NIPH Clinical Trials: Long-term comparison of luseogliflozin vs sitagliptin for Type 2 diabetes mellitus patients with NASH/NAFLD
• Chemical Composition and Structure: It's structure consists of a triazolopyrazine core with trifluoromethyl and phenyl groups.
• Uses: Sitagliptin phosphate monohydrate is categorized as a dipeptidyl peptidase-4 (DPP-4) inhibitor and is used in the treatment of type 2 diabetes mellitus.
• Mechanism of Action: Sitagliptin is a β-amino acid-derived inhibitor of dipeptidyl peptidase 4 (DPP-4), which regulates insulin and blood glucose concentration by inhibiting the degradation of incretins such as GLP-1.^[2]
• Approved Indications: Sitagliptin phosphate monohydrate was the first DPP-4 inhibitor to receive marketing authorization. Sitagliptin phosphate monohydrate is approved by regulatory agencies such as the FDA and EMA for the treatment of type 2 diabetes mellitus.^[1]
• References: [1] A highly sensitive LC-MS/MS method for the determination and quantification of a recently identified N-nitrosamine impurity in the sitagliptin phosphate monohydrate active pharmaceutical ingredient; DOI 10.1039/D2AY01821G; [2] Sitagliptin Phosphate Monohydrate. In: Signposts to Chiral Drugs.; DOI 10.1007/978-3-0348-0125-6_4

Technology Process of Sitagliptin phosphate monohydrate

There total 16 articles about Sitagliptin phosphate monohydrate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.7%

sitagliptin (486460-32-6,823817-55-6) → sitagliptin phosphate monohydrate (654671-77-9)

Guidance literature:

With phosphoric acid; In water; isopropyl alcohol; at 70 - 80 ℃; for 2h; Temperature;

Reference yield:

1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione (764667-65-4) → sitagliptin phosphate monohydrate (654671-77-9)

Guidance literature:

Multi-step reaction with 4 steps

1: isopropyl alcohol; acetic acid / 18 h / 50 °C

2: sodium tetrahydroborate; formic acid / tetrahydrofuran / -30 °C

3: 20% palladium hydroxide-activated charcoal; hydrogen; acetic acid / methanol; water / 14 h / 50 °C / 7500.75 Torr

4: phosphoric acid; water / isopropyl alcohol / 20 - 75 °C

With sodium tetrahydroborate; formic acid; phosphoric acid; 20% palladium hydroxide-activated charcoal; water; hydrogen; acetic acid; In tetrahydrofuran; methanol; water; acetic acid; isopropyl alcohol;

DOI:10.1080/00397911.2013.773353

Reference yield:

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → sitagliptin phosphate monohydrate (654671-77-9)

Guidance literature:

Multi-step reaction with 7 steps

1.1: triethylamine; magnesium chloride / acetonitrile / 30 - 50 °C / Inert atmosphere

1.2: 5.5 h / 30 °C / Inert atmosphere

2.1: hydrogen; dichloro[(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]ruthenium(II) / methanol; acetic acid / 70 °C / 3620.13 Torr / Inert atmosphere; Autoclave

3.1: lithium hydroxide; dicyclohexyl-carbodiimide / tetrahydrofuran; water; cis-1,2-Dichloroethylene / 3 h / 20 - 22 °C

3.2: 18.5 h / 10 - 20 °C

4.1: lithium hydroxide / tetrahydrofuran; water / 2.33 h / 20 - 25 °C / pH 3

4.2: 3 h / 0 - 5 °C

5.1: phosphoric acid / isopropyl alcohol / 16 h / 30 °C

6.1: sodium hydroxide / water / 1 h / 0 - 5 °C

7.1: phosphoric acid; water / water; isopropyl alcohol / 0.25 h

With dichloro[(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]ruthenium(II); phosphoric acid; water; hydrogen; triethylamine; dicyclohexyl-carbodiimide; sodium hydroxide; magnesium chloride; lithium hydroxide; In tetrahydrofuran; cis-1,2-Dichloroethylene; methanol; water; acetic acid; isopropyl alcohol; acetonitrile;

upstream raw materials:

sitagliptin

1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione

(R,Z)-3-[(1-phenylethyl)amino]-1-{3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)but-2-en-1-one

(3R)-3-[[(1R)-1-phenylethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one

Downstream raw materials:

sitagliptin phosphate

Refernces

• 1、 -. "A phosphoric acid west geleg sandbank crystal and its preparation and use". Paragraph 0070; 0077; 0080; 0083; 0086; 0089; 0092; 0095. . Retrieved 2018/11/03.
• 2、 -. "SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF". Paragraph 0204. . Retrieved 2013/06/28.