AVL-292

Base Information

• Chemical Name: AVL-292
• CAS No.: 1202757-89-8
• Molecular Formula: C22H22FN5O3
• Molecular Weight: 423.447
• Mol file: 1202757-89-8.mol

Synonyms:AVL-292;LMK-435;N-[3-[[5-Fluoro-2-[[4-(2-methoxyethoxy)phenyl]amino]-4-pyrimidinyl]amino]phenyl]-2-propenamide;2-Propenamide, N-[3-[[5-fluoro-2-[[4-(2-methoxyethoxy)phenyl]amino]-4-pyrimidinyl]amino]phenyl]-;CC-292 (AVL-292);CC-292,LMK-435;N-[3-[[5-Fluoro-2-[[4-(2-methoxyethoxy)phenyl]amino]-4-pyrimidinyl]amino]phenyl]-2-propenamide AVL292;CC-292

Chemical Property of AVL-292

Chemical Property:

• PKA: 13.22±0.70(Predicted)
• PSA: 97.40000
• Density: 1.322±0.06 g/cm3(Predicted)
• LogP: 4.47160
• Solubility.: ≥21.15 mg/mL in DMSO; insoluble in H2O; ≥4.9 mg/mL in EtOH with gentle warming and ultrasonic

Purity/Quality:

98%,99%, ^*data from raw suppliers

AVL-292 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase involved in signal transduction pathways regulating the proliferation, activation, and differentiation of B cells. AVL-292 is an orally available, selective, and irreversible inhibitor of BTK (IC50 = 0.5 nM in vitro in B cell lymphoma cell lines) that targets and covalently binds to BTK at cysteine-481, thereby preventing its activity. AVL-292 has been shown to inhibit osteoclast function and to reduce osteoclast-stimulated proliferation of multiple myeloma cells in animal models of rheumatoid arthritis and multiple sclerosis, both of which are diseases where B cells play an important role. In clinical trials, AVL-292 has demonstrated therapeutic significance in the treatment of both B cell-related cancers (e.g., non-Hodgkin’s lymphoma and B cell chronic lymphocytic leukemia) and autoimmune diseases (e.g., rheumatoid arthritis).[Cayman Chemical]

Technology Process of AVL-292

There total 10 articles about AVL-292 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: 80.0%

N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine (1202759-91-8) + acryloyl chloride (814-68-6,25189-84-8) → N-(3-{5-fluoro-2-[4-(2-methoxy-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-phenyl)-acrylamide (1202757-89-8)

Guidance literature:

N⁴-(3-aminophenyl)-5-fluoro-N²-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine; acryloyl chloride; In tetrahydrofuran; at -10 ℃;

With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 0.166667h;

Reference yield: 64.0%

C15H12F7N3O8S2 + Ν-(3-aminophenyl)prop-2-enamide (16230-24-3) → N-(3-{5-fluoro-2-[4-(2-methoxy-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-phenyl)-acrylamide (1202757-89-8)

Guidance literature:

With potassium hydrogencarbonate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 25 ℃; for 0.5h; Reagent/catalyst;

Reference yield:

tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (1202759-89-4) → N-(3-{5-fluoro-2-[4-(2-methoxy-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-phenyl)-acrylamide (1202757-89-8)

Guidance literature:

Multi-step reaction with 3 steps

1: toluene-4-sulfonic acid / ethanol / 24 h / Reflux

2: trifluoroacetic acid / dichloromethane / 0.75 h / 0 °C

3: dichloromethane / -30 °C

With toluene-4-sulfonic acid; trifluoroacetic acid; In ethanol; dichloromethane;

upstream raw materials:

N⁴-(3-aminophenyl)-5-fluoro-N²-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine

acryloyl chloride

4-(2-methoxyethoxy)aniline

tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino) pyrimidin-4-yl)amino)phenyl)carbamate

Downstream raw materials:

3-((3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate

N-(3-((5-fluoro-2-((4-(2-methoxyethoxyl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamide

N-(3-(5-fluoro-2-(4-(2-methoxyethoxyl)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide besylate

Refernces

• 1、 -. "HETEROARYL COMPOUNDS AND USES THEREOF". Paragraph 0629. . Retrieved 2015/07/02.
• 2、 -. "HETEROARYL COMPOUNDS AND USES THEREOF". Page/Page column 190; 192. . Retrieved 2010/01/30.