(2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine

Base Information

• Chemical Name: (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine
• CAS No.: 767340-03-4
• Molecular Formula: C16H13F6N5O
• Molecular Weight: 405.303
• Hs Code.: 2933990090
• Mol file: 767340-03-4.mol

Synonyms:1,2,4-Triazolo[4,3-a]pyrazine,7-[(2Z)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)-2-butenyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-(9CI);(2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine;(2Z)-3-Amino-1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)-2-buten-1-one;

Chemical Property of (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine

Chemical Property:

• Melting Point: 178-180°C
• Refractive Index: 1.59
• Boiling Point: 555.1 °C at 760 mmHg
• PKA: 4.11±0.70(Predicted)
• Flash Point: 289.5 °C
• PSA: 77.04000
• Density: 1.6 g/cm³
• LogP: 2.77990
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

99% ^*data from raw suppliers

(2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Sitagliptin intermediate. A dipeptidyl peptidase-4 inhibitor and an anti-hypertensive agent for the treatment of diabetes and hypertension.

Technology Process of (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine

There total 12 articles about (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine 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: 92.0%

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) → (Z)-3-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 (767340-03-4)

Guidance literature:

With ammonium hydroxide; ammonium acetate; In methanol; at 58 ℃; for 0.5h;

DOI:10.1039/d0ra10273c

Reference yield:

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → (Z)-3-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 (767340-03-4)

Guidance literature:

Multi-step reaction with 3 steps

1.1: dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine / ISOPROPYLAMIDE / 2 - 3 h / 0 - 40 °C

2.1: ISOPROPYLAMIDE / 40 - 70 °C

2.2: 20 - 45 °C

3.1: ammonium acetate; ammonia / methanol; water / 2 h / 30 °C / Heating / reflux

With dmap; ammonium acetate; ammonia; pivaloyl chloride; N-ethyl-N,N-diisopropylamine; In methanol; ISOPROPYLAMIDE; water;

Reference yield:

5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (764667-64-3) → (Z)-3-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 (767340-03-4)

Guidance literature:

Multi-step reaction with 2 steps

1.1: ISOPROPYLAMIDE / 40 - 70 °C

1.2: 20 - 45 °C

2.1: ammonium acetate; ammonia / methanol; water / 2 h / 30 °C / Heating / reflux

With ammonium acetate; ammonia; In methanol; ISOPROPYLAMIDE; water;

upstream raw materials:

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

2,2,2-trifluoro-N’-[(2Z)-piperazin-2-ylidene]acetohydrazide

(2,4,5-trifluorophenyl)acetic acid

5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione

Downstream raw materials:

(Z)-tert-butyl-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)-but-2-en-2-ylcarbamate

sitagliptin phosphate monohydrate

sitagliptin phosphate

(R/S)-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

Refernces

• 1、 -. "NEW EFFICIENT PROCESS FOR THE PREPARATION OF SITAGLIPTIN.". Paragraph 0174. . Retrieved 2019/09/06.
• 2、 -. "PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES". Page/Page column 53. . Retrieved 2010/11/05.