Siponimod

Base Information

• Chemical Name: Siponimod
• CAS No.: 1230487-00-9
• Deprecated CAS: 1220909-40-9
• Molecular Formula: C29H35F3N2O3
• Molecular Weight: 516.604
• UNII: RR6P8L282I
• DSSTox Substance ID: DTXSID40153847
• Wikipedia: Siponimod
• NCI Thesaurus Code: C152368
• RXCUI: 2121085
• Pharos Ligand ID: MNH4Z54W3PQH
• Metabolomics Workbench ID: 153369
• ChEMBL ID: CHEMBL2336071
• Mol file: 1230487-00-9.mol

Synonyms:1-(4-(1-((E)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino)-ethyl)-2-ethylbenzyl)-azetidine-3-carboxylic acid;BAF-312;BAF312;Mayzent;siponimod

Chemical Property of Siponimod

Chemical Property:

• Boiling Point: 602.0±65.0 °C(Predicted)
• PKA: 2.69±0.20(Predicted)
• PSA: 62.13000
• Density: 1.24±0.1 g/cm3(Predicted)
• LogP: 6.71060
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 4.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 9
• Exact Mass: 516.25997747
• Heavy Atom Count: 37
• Complexity: 777

Purity/Quality:

99% ^*data from raw suppliers

Siponimod ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Multiple Sclerosis Agents
• Canonical SMILES: CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
• Isomeric SMILES: CCC1=C(C=CC(=C1)/C(=N/OCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)/C)CN4CC(C4)C(=O)O
• Recent ClinicalTrials: Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients
• Recent EU Clinical Trials: Effect of siponimod on relevant imaging and immunological hallmarks of progressive multiple sclerosis
• Recent NIPH Clinical Trials: Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
• Description: S1p signaling is important for immune, cardiovascular, and CNS function.Like its FDA approved predecessor fingolimod, siponimod is an oral S1p signaling modulator.While fin- golimod binds four out of five known S1p receptors, siponimod is selective for receptor sub- types 1 and 5. This selectivity may allow for an improved adverse event profile.
• Uses: Siponimod is a functional sphingosine -1 phosphate (SIP) antagonist used in the treatment of multiple sclerosis and other central nervous system-related diseases in human subjects. .

Technology Process of Siponimod

There total 43 articles about Siponimod 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: 89.0%

4-[(1E)-1-([[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino)ethyl]-2-ethylbenzaldehyde (1230487-01-0) + 3-azetidinecarboxylic acid (36476-78-5) → Siponimod (1230487-00-9)

Guidance literature:

4-[(1E)-1-([[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino)ethyl]-2-ethylbenzaldehyde; 3-azetidinecarboxylic acid; In methanol; at 20 - 25 ℃; for 0.5h;

With methanol; sodium tris(acetoxy)borohydride;

Reference yield: 70.0%

(E)-1-(3-ethyl-4-(hydroxymethyl)phenyl)ethan-1-one-O-(4-cyclohexyl-3-(trifluoromethyl)benzyl)-oxime (1418144-66-7) + 3-azetidinecarboxylic acid (36476-78-5) → Siponimod (1230487-00-9)

Guidance literature:

(E)-1-(3-ethyl-4-(hydroxymethyl)phenyl)ethan-1-one-O-(4-cyclohexyl-3-(trifluoromethyl)benzyl)-oxime; With manganese(IV) oxide; In 1,4-dioxane; for 0.5h; Reflux;

3-azetidinecarboxylic acid; With acetic acid; In methanol; at 20 ℃; for 0.333333h;

With sodium cyanoborohydride; In methanol; at 20 ℃; for 1h;

DOI:10.1021/ml300396r

Reference yield:

1-bromo-4-methyl-2-(trifluoromethyl)benzene (261952-20-9) → Siponimod (1230487-00-9)

Guidance literature:

Multi-step reaction with 10 steps

1.1: bis-triphenylphosphine-palladium(II) chloride; sodium methylate / methanol / 100 °C

2.1: hydrogen; 5%-palladium/activated carbon / methanol / 16 h / 60 °C / 3750.38 Torr

3.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / n-heptane; acetonitrile / 80 °C

4.1: isopropylmagnesium chloride / tetrahydrofuran / Inert atmosphere

4.2: -5 - 5 °C / Inert atmosphere

4.3: -5 - 5 °C / Inert atmosphere

5.1: lithium aluminium tetrahydride / tetrahydrofuran; toluene / 20 - 25 °C

6.1: hydrogen bromide; acetic acid / 20 - 30 °C

6.2: 20 - 25 °C

7.1: dmap; potassium carbonate / dichloromethane; acetone / 50 - 52 °C

8.1: hydrogenchloride / methanol / 20 - 25 °C

8.2: 20 - 25 °C / pH 0 - 4.5

9.1: manganese(IV) oxide / n-heptane / 50 - 55 °C

10.1: methanol / 0.5 h / 20 - 25 °C

10.2: 20 - 25 °C

With hydrogenchloride; dmap; manganese(IV) oxide; bis-triphenylphosphine-palladium(II) chloride; N-Bromosuccinimide; lithium aluminium tetrahydride; 2,2'-azobis(isobutyronitrile); 5%-palladium/activated carbon; hydrogen bromide; hydrogen; isopropylmagnesium chloride; sodium methylate; potassium carbonate; acetic acid; In tetrahydrofuran; methanol; n-heptane; dichloromethane; acetone; toluene; acetonitrile; 1.1: |Suzuki Coupling;

upstream raw materials:

4-[(1E)-1-([[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino)ethyl]-2-ethylbenzaldehyde

3-azetidinecarboxylic acid

3-bromo-4-methylacetophenone

1-[3-bromo-4-(hydroxymethyl)phenyl]ethan-1-one

Refernces

• 1、 -. "SOLID FORMS OF SIPONIMOD". Page/Page column 14; 15. . Retrieved 2020/10/21.
• 2、 -. "SOLID STATE FORMS OF SIPONIMOD". Page/Page column 14. . Retrieved 2020/09/12.