Crenolanib

Base Information

• Chemical Name: Crenolanib
• CAS No.: 670220-88-9
• Molecular Formula: C26H29N5O2
• Molecular Weight: 443.549
• UNII: LQF7I567TQ
• DSSTox Substance ID: DTXSID50985873
• Nikkaji Number: J3.198.440H
• Wikipedia: Crenolanib
• Wikidata: Q5184160
• NCI Thesaurus Code: C64639
• Pharos Ligand ID: BG4M6C68MQDH
• Metabolomics Workbench ID: 152926
• ChEMBL ID: CHEMBL2105728
• Mol file: 670220-88-9.mol

Synonyms:CP-868,596;crenolanib

Chemical Property of Crenolanib

Chemical Property:

• Boiling Point: 676.6±65.0 °C(Predicted)
• PKA: 9.84±0.20(Predicted)
• PSA: 78.43000
• Density: 1.36
• LogP: 4.68180
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 15 mg/ml) or in Ethanol (up to 10 mg/ml).
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 443.23212518
• Heavy Atom Count: 33
• Complexity: 667

Purity/Quality:

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

Crenolanib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
• Recent ClinicalTrials: Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations
• Recent EU Clinical Trials: Phase III Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy of the Addition of Crenolanib to Salvage Chemotherapy Versus Salvage Chemotherapy Alone in Subjects ≤ 75 Years of Age with Relapsed/Refractory FLT3 Mutated Acute Myeloid Leukemia
• Description: Crenolanib (670220-88-9) is a potent inhibitor of PDGFR (Kd?for α = 2.1 nM; β = 3.2 nM) and FLT3 (Kd?= 0.74 nM).1?Crenolanib is a type I inhibitor binding only to the active kinase conformation. It showed potent activity against imatinib-resistant PDGFRα mutations D842I, D842V, D842Y, DI842-843M, and deletion I8432?as well as FLT3/ITD and FLT3/D835 mutants3. Crenolanib acted synergistically with FLT3-CAR T-cells in a FLT3-ITD+?AML murine xenograft model.4
• Uses: Crenolanib (CP-868569) is a highly selective and potent PDGFR-α inhibitor with IC50 of 0.9 and 1.8 nM against PDGFRα and PDGFRβ, respectively. Crenolanib (CP-868569) is a tyrosine kinase inhibitor that acts by specifically inhibiting the receptor tyrosine kinases PDGFRα and PDGFRβ. Crenolanib (CP-868569) inhibits the activity of PDGFRα D842V kinase and prevented the phosphorylation of wild type PDGFRα. Crenolanib (CP-868569) possesses potential antineoplastic activity. Crenolanib is believed to suppress PDGFR-related signal transduction pathways leading to the inhibition of tumor angiogenesis and tumor cell proliferation. Crenolanib is an orally bioavailable, selective inhibitor of type III tyrosine kinases with nanomolar potencies against platelet-derived growth factor receptor α (PDGFRα) and PDGFRβ and Fms-related tyrosine kinase 3 (FLT3; IC50s = 11, 3.2, and 4 nM, respectively). It also inhibits medically-relevant mutant forms of these kinases, including the D842V-containing form of PDGFR and D835Y and internal tandem duplication mutations of FLT3, at nanomolar concentrations. Crenolanib is more than 100-fold selective for these kinases over other tyrosine and serine/threonine kinases. It is effective when used in cells and in vivo.[Cayman Chemical]

Technology Process of Crenolanib

There total 10 articles about Crenolanib 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: 98.77%

tert-butyl N-[1-(2-{5-[(3-methyloxetan-3-yl)methoxy]-1H-1,3-benzodiazol-1-yl}quinolin-8-yl)piperidin-4-yl]carbamate (816463-40-8) → 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine (670220-88-9)

Guidance literature:

With 2-methyltetrahydrofuran; sodium ethanolate; In water; Reflux;

Reference yield: 86.0%

1-{2-[5-(3-methyloxetan-3-ylmethoxy)benzoimidazol-1-yl]quinolin-8-yl}piperidin-4-ylamine citrate → 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine (670220-88-9)

Guidance literature:

With sodium hydroxide; pH=10 - 12;

Reference yield:

3-hydroxymethyl-3-methyloxethane (3143-02-0) → 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine (670220-88-9)

Guidance literature:

Multi-step reaction with 6 steps

1.1: sodium / tetrahydrofuran / 4 h / 66 °C

1.2: 24 h / 50 - 60 °C

2.1: potassium carbonate; 1,2-bis-(diphenylphosphino)ethane; palladium diacetate / toluene / 98 - 100 °C

3.1: triethylamine; palladium on activated charcoal / ethanol / 0.67 h / 45 °C

3.2: 50 - 55 °C

4.1: pyridine / N,N-dimethyl-formamide / 25 - 30 °C

5.1: potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / toluene / 20 - 85 °C

6.1: sodium ethanolate; 2-methyltetrahydrofuran / water / Reflux

With 2-methyltetrahydrofuran; pyridine; palladium on activated charcoal; sodium ethanolate; palladium diacetate; sodium; potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; triethylamine; 1,2-bis-(diphenylphosphino)ethane; In tetrahydrofuran; ethanol; water; N,N-dimethyl-formamide; toluene;

upstream raw materials:

tert-butyl N-[1-(2-{5-[(3-methyloxetan-3-yl)methoxy]-1H-1,3-benzodiazol-1-yl}quinolin-8-yl)piperidin-4-yl]carbamate

3-hydroxymethyl-3-methyloxethane

4-Chloro-2-nitroaniline

5-hydroxy-1H-benzimidazole

Downstream raw materials:

crenolanib besylate

Refernces

• 1、 -. "Synthesis method of drug for treating leukemia". Paragraph 0017. . Retrieved 2018/03/01.
• 2、 -. "PROCESSES FOR THE PREPARATION OF 1-[(BENZOIMIDAZOLE-1YL) QUINOLIN-8-YL] PIPERIDIN-4-YLAMINE DERIVATIVES". Page 16. . Retrieved 2008/06/13.