AMG-3969

Base Information

• Chemical Name: AMG-3969
• CAS No.: 1361224-53-4
• Molecular Formula: C₂₁H₂₀F₆N₄O₃S
• Molecular Weight: 522.471
• Hs Code.: 2935909099
• Mol file: 1361224-53-4.mol

Synonyms:2-(4-((2S)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Chemical Property of AMG-3969

Chemical Property:

• Boiling Point: 648.8±65.0 °C(Predicted)
• PKA: 10.12±0.15(Predicted)
• Density: 1.56±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)

Purity/Quality:

99% ^*data from raw suppliers

AMG-3969 >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: AMG-3969is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor. Itcan strongly boost the dissociation of the GK-GKRP complex and promote GK translocation in-vivo. In rodent model of diabetes, AMG-3969 reduces blood glucose levels without affecting euglycemic animals. It is a promising drug for the treatment of type II diabetes through lowering blood glucose levels with reduced potential for hypoglycaemic risk.

Technology Process of AMG-3969

There total 22 articles about AMG-3969 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:

benzyl (2-((tert-butoxycarbonyl)amino)ethyl)(2-oxo-3-pentyn-1-yl)-carbamate (1361224-49-8) → 2-(4-((2R)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-54-5) + 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-53-4)

Guidance literature:

Multi-step reaction with 5 steps

1.1: trifluoroacetic acid / dichloromethane / -10 - 20 °C

1.2: 2 h

2.1: sodium t-butanolate / ruphos; chloro(2-dicyclohexylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct / toluene / 1.5 h / 100 °C / sealed vessel; Inert atmosphere

3.1: trifluoroacetic acid; trifluorormethanesulfonic acid / 0.25 h / 20 °C

3.2: pH ~ 7

4.1: triethylamine / dichloromethane / 0.33 h / 20 °C

5.1: Chiralpak^.(R). ADH column / carbon dioxide; methanol / Resolution of racemate

With trifluorormethanesulfonic acid; triethylamine; trifluoroacetic acid; sodium t-butanolate; chloro(2-dicyclohexylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct; ruphos; In methanol; dichloromethane; carbon dioxide; toluene;

Reference yield:

benzyl 3-(propan-1-yn-1-yl)piperazine-1-carboxylate (1361224-50-1) → 2-(4-((2R)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-54-5) + 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-53-4)

Guidance literature:

Multi-step reaction with 4 steps

1.1: sodium t-butanolate / ruphos; chloro(2-dicyclohexylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct / toluene / 1.5 h / 100 °C / sealed vessel; Inert atmosphere

2.1: trifluoroacetic acid; trifluorormethanesulfonic acid / 0.25 h / 20 °C

2.2: pH ~ 7

3.1: triethylamine / dichloromethane / 0.33 h / 20 °C

4.1: Chiralpak^.(R). ADH column / carbon dioxide; methanol / Resolution of racemate

With trifluorormethanesulfonic acid; triethylamine; trifluoroacetic acid; sodium t-butanolate; chloro(2-dicyclohexylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct; ruphos; In methanol; dichloromethane; carbon dioxide; toluene;

Reference yield:

2-(4-(4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-48-7) → 2-(4-((2R)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-54-5) + 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1361224-53-4)

Guidance literature:

With Chiralpak ADH column; In methanol; carbon dioxide; Purification / work up; Resolution of racemate;

upstream raw materials:

6-Amino-3-pyridinesulfonyl Chloride

1,1,1,3,3,3-hexafluoro-2-(4-(2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-2-propanol

2-aminopyridine

2-(4-(4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Downstream raw materials:

2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-((1Z)-1-propen-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Refernces

• 1、 Bourbeau, Matthew P.,Ashton, Kate S.,Yan, Jie,St. Jean, David J.. "Nonracemic synthesis of GK-GKRP disruptor AMG-3969". . p. 3684 - 3687. Retrieved 2014/05/06.
• 2、 Lloyd, David J.,St Jean, David J.,Kurzeja, Robert J. M.,Wahl, Robert C.,Michelsen, Klaus,Cupples, Rod,Chen, Michelle,Wu, John,Sivits, Glenn,Helmering, Joan,Komorowski, Renee,Ashton, Kate S.,Pennington, Lewis D.,Fotsch, Christopher,Vazir, Mukta,Chen, Kui,Chmait, Samer,Zhang, Jiandong,Liu, Longbin,Norman, Mark H.,Andrews, Kristin L.,Bartberger, Michael D.,Van, Gwyneth,Galbreath, Elizabeth J.,Vonderfecht, Steven L.,Wang, Minghan,Jordan, Steven R.,Veniant, Murielle M.,Hale, Clarence. "Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors". . p. 437 - 440. Retrieved 2014/01/06.