RN486

Base Information

• Chemical Name: RN486
• CAS No.: 1242156-23-5
• Molecular Formula: C35H35FN6O3
• Molecular Weight: 606.7
• Mol file: 1242156-23-5.mol

Synonyms:6-Cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one;RN 486;QCR-5;6-cyclopropyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoquinolin-1(2H)-one;

Chemical Property of RN486

Chemical Property:

• Boiling Point: 868.6±65.0 °C(Predicted)
• PKA: 13.95±0.10(Predicted)
• PSA: 95.63000
• Density: 1.378±0.06 g/cm3(Predicted)
• LogP: 4.83150
• Solubility.: ≥30.35 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH

Purity/Quality:

98%min ^*data from raw suppliers

RN486 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: RN 486 is a Bruton’s tyrosine kinase (Btk) inhibitor, blocking receptor cross-linking-induced degranulation in mast cells. May be used in the prevention of arthritis and other autoimmune diseases.

Technology Process of RN486

There total 16 articles about RN486 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: 83.0%

2-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinoline-1(2H)-one (1242156-55-3) + 1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (1242156-62-2) → 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (1242156-23-5)

Guidance literature:

With potassium carbonate; tricyclohexylphosphine; palladium diacetate; In 1,4-dioxane; water; at 70 - 88 ℃; Inert atmosphere of nitrogen; Reflux;

Reference yield:

6-bromo-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one (1242157-15-8) → 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (1242156-23-5)

Guidance literature:

Multi-step reaction with 5 steps

1: tricyclohexylphosphine; palladium diacetate; potassium phosphate / toluene; water / 4 h / 100 °C / Inert atmosphere

2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 1,4-dioxane / 18 h / 100 °C / Inert atmosphere; Sealed tube

3: caesium carbonate; copper(l) iodide / 1,4-dioxane / 18 h / Inert atmosphere; Sealed tube; Heating

4: alkali borohydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere

5: tricyclohexylphosphine; palladium diacetate; potassium carbonate / 1,4-dioxane / 3 h / 88 °C / Inert atmosphere

With potassium phosphate; copper(l) iodide; palladium diacetate; potassium carbonate; caesium carbonate; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tricyclohexylphosphine; In tetrahydrofuran; 1,4-dioxane; water; toluene; 1: |Suzuki Coupling / 5: |Suzuki Coupling;

DOI:10.1021/jm500305p

Reference yield:

6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one (1242157-16-9) → 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (1242156-23-5)

Guidance literature:

Multi-step reaction with 4 steps

1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 1,4-dioxane / 18 h / 100 °C / Inert atmosphere; Sealed tube

2: caesium carbonate; copper(l) iodide / 1,4-dioxane / 18 h / Inert atmosphere; Sealed tube; Heating

3: alkali borohydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere

4: tricyclohexylphosphine; palladium diacetate; potassium carbonate / 1,4-dioxane / 3 h / 88 °C / Inert atmosphere

With copper(l) iodide; palladium diacetate; potassium carbonate; caesium carbonate; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tricyclohexylphosphine; In tetrahydrofuran; 1,4-dioxane; 4: |Suzuki Coupling;

DOI:10.1021/jm500305p

upstream raw materials:

2-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinoline-1(2H)-one

1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one

6-bromo-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one

6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one

Refernces

• 1、 -. "Inhibitors of Bruton's Tyrosine Kinase". Page/Page column 59-60. . Retrieved 2010/09/07.