Development of a Scalable Synthesis for the Potent Kinase Inhibitor BMS-986236; 1-(5-(4-(3-Hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile

被引：6

作者：

Arunachalam, Pirama Nayagam ^{[1
]}

Kuppusamy, Prakasam ^{[1
]}

Ganesan, Sivakumar ^{[1
]}

Krishnamoorthy, Suresh ^{[1
]}

Nimje, Roshan Y. ^{[1
]}

Jarugu, Lokesh Babu ^{[1
]}

Chikkananjaiah, Nanjundaswamy Kanikahalli ^{[1
]}

Reddy, China Anki ^{[1
]}

Anjanappa, Prakash ^{[1
]}

Botlagunta, Murali ^{[1
]}

Vanteru, Sridhar ^{[1
]}

Maddala, Nageswararao ^{[1
]}

Shankar, Muniyappa ^{[1
]}

Nair, Satheesh ^{[1
]}

Hynes, John, Jr. ^{[2
]}

Santella, Joseph B., III ^{[2
]}

Carter, Percy H. ^{[2
]}

Rampulla, Richard ^{[2
]}

Vetrichelvan, Muthalagu ^{[1
]}

Gupta, Anuradha ^{[1
]}

Gupta, Arun Kumar ^{[1
]}

Mathur, Arvind ^{[2
]}

机构：

[1] Biocon Bristol Myers Squibb Res Ctr, Dept Discovery Synth, Biocon Pk,Bommasandra 4 Phase,Jigani Link Rd, Bangalore 560099, Karnataka, India

[2] Bristol Myers Squibb, Discovery Chem, POB 5400, Princeton, NJ 08543 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 05期

关键词：

kinase inhibitor; scalable synthesis; DSC studies; azide; triazole; 1H-pyrazolor[3,4-b]pyridine derivative; RATIONAL DESIGN; 1,2,3-TRIAZOLES; HYDRAZINE; REDUCTION;

D O I：

10.1021/acs.oprd.9b00023

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A scalable route to 1-(5-(4-(3-hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (1, BMS-986236) was developed by incorporating an alternate azide intermediate following safety-driven processes. The newly developed process involved mitigating safety hazards and eliminating the column chromatography purification. The issue of trace metal contamination in the final API observed in the first-generation synthesis has been overcome.

引用

页码：912 / 918

页数：7

共 27 条

[1] Efficient one-pot synthesis of 1-aryl 1,2,3-triazoles from aryl halides and terminal alkynes in the presence of sodium azide [J].