Upadacitinib

Base Information

• Chemical Name: Upadacitinib
• CAS No.: 1310726-60-3
• Molecular Formula: C17H19F3N6O
• Molecular Weight: 380.373
• Mol file: 1310726-60-3.mol

Synonyms:Upadacitinib;ABT-494

Chemical Property of Upadacitinib

Chemical Property:

• PKA: 11.89±0.60(Predicted)
• PSA: 78.32000
• Density: 1.56±0.1 g/cm3(Predicted)
• LogP: 3.23670

Purity/Quality:

99% ^*data from raw suppliers

Upadacitinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Upadacitinib is a JAK1 inhibitor (IC50 = 47 nM). It is selective for JAK1 over JAK3 and tyrosine kinase 2 (Tyk2; IC50s = 2,304 and 4,690 nM, respectively), as well as a panel of 83 additional kinases at 1 μM, but does inhibit JAK2, Rho-associated kinase I (ROCK1), and ROCK2 (IC50s = 120, 920, and 430 nM, respectively). Upadacitinib decreases cytokine-induced STAT phosphorylation in a variety of human cells with IC50 values ranging from 1.6 to 649 nM. It reduces M. tuberculosis-induced paw swelling and bone erosion in a rat model of arthritis when administered at doses of 1, 3, and 10 mg/kg twice per day for 17 days. Formulations containing upadacitinib have been used in the treatment of rheumatoid arthritis. Upadacitinib (ABT-494) is a JAK1 selective inhibitor being investigated to treat rheumatoid arthritis, Crohn's disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, axial SpA Giant Cell Arteritis and Takayasu Arteritis.
• Uses: Upadacitinib also known as ABT-494, is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, Janus kinase inhibitors for rheumatoid arthritis.
• Clinical Use: Upadacitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate.

Technology Process of Upadacitinib

There total 100 articles about Upadacitinib 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: 95.0%

C22H27F3N6O3 → (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (1310726-60-3)

Guidance literature:

With butan-1-ol; at 85 - 90 ℃;

Reference yield: 92.0%

N-(2,2,2-trifluoroethyl)-1H-imidazole-1-carboxamide (1046861-47-5) + 8-((3R,4S)-4-ethylpyrrolidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine bishydrochloride → (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (1310726-60-3)

Guidance literature:

8-((3R,4S)-4-ethylpyrrolidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine bishydrochloride; With dipotassium hydrogenphosphate; potassium hydroxide; In 2-methyltetrahydrofuran; water; at 25 ℃; pH=9.0; Inert atmosphere; Large scale;

N-(2,2,2-trifluoroethyl)-1H-imidazole-1-carboxamide; In tetrahydrofuran; 2-methyltetrahydrofuran; water; at 25 ℃; for 2h; pH=9.0; Inert atmosphere; Large scale;

DOI:10.1021/acs.oprd.1c00287

Reference yield: 88.0%

trifluoroethylamine (753-90-2) + (3S,4R)-benzyl-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)pyrrolidine-1-carboxylate → (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (1310726-60-3)

Guidance literature:

(3S,4R)-benzyl-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)pyrrolidine-1-carboxylate; With 2,6-dichloropyridine; trifluoromethylsulfonic anhydride; In dichloromethane; at 0 - 20 ℃; Inert atmosphere;

trifluoroethylamine; In dichloromethane; at 20 ℃; Inert atmosphere;

upstream raw materials:

trifluoroethylamine

1,1'-carbonyldiimidazole

(3R,4S)-benzyl 3-(2-bromoacetyl)-4-ethylpyrrolidine-1-carboxylate

2-bromo-5-(p-toluenesulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Refernces

• 1、 Bhagavatula, Lakshmi,Christesen, Alan,Dunn, Travis B.,Ickes, Andrew,Kotecki, Brian J.,Marek, James C.,Morrill, Westin H.,Moschetta, Eric,Mulhern, Mathew,Rasmussen, Michael,Reynolds, Troy,Rozema, Michael J.,Yu, Su. "Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib". . . Retrieved 2021/10/21.
• 2、 -. "PYRROLIDINE COMPOUNDS, ITS SALT AND USE IN THE PREPARATION OF UPADACITINIB THEREOF". . . Retrieved 2021/01/29.