Volasertib

Base Information

• Chemical Name: Volasertib
• CAS No.: 755038-65-4
• Molecular Formula: C₃₄H₅₀N₈O₃
• Molecular Weight: 618.823
• European Community (EC) Number: 813-258-1
• UNII: 6EM57086EA
• DSSTox Substance ID: DTXSID901025694,DTXSID801099395
• Nikkaji Number: J2.963.994I
• Wikipedia: Volasertib
• Wikidata: Q7939986
• NCI Thesaurus Code: C79844
• Pharos Ligand ID: YPVS3GFVNJGB
• ChEMBL ID: CHEMBL1233528,CHEMBL4284151
• Mol file: 755038-65-4.mol

Synonyms:BI 6727;BI-6727;volasertib

Chemical Property of Volasertib

Chemical Property:

• PKA: 14.26±0.40(Predicted)
• PSA: 106.17000
• Density: 1.26
• LogP: 4.73690
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml).
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 10
• Exact Mass: 618.40058749
• Heavy Atom Count: 45
• Complexity: 996

Purity/Quality:

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

Volasertib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C
• Isomeric SMILES: CC[C@@H]1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C
• Recent ClinicalTrials: Volasertib in Combination With Low-dose Cytarabine in Patients Aged 65 Years and Above With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy (POLO-AML-2)
• Recent EU Clinical Trials: Open-label, dose-escalating trial to evaluate the tolerability, toxicity, safety, pharmacokinetics, pharmacodynamics and activity of volasertib added to the standard intensive salvage chemotherapy regimen with liposomal daunorubicine, fludarabine and cytarabine (DNX-FLA) followed by fludarabine and cytarabine (FLA) in children from 3 months to less than 18 years of age with acute myeloid leukaemia after failure of the front-line therapy
• Description: Volasertib (BI 6727) is a highly potent Plk1 inhibitor with IC50 of 0.87 nM in a cell-free assay. It shows 6-and 65-fold greater selectivity against Plk2 and Plk3. Phase 3. Volasertib (755038-65-4) is an extremely potent and selective inhibitor (IC50’s: Plk1= 0.87 nM, Plk2 = 5 nM, Plk3 = 56 nM) of Polo-like kinase 1, a critical controller of multiple essential steps of mitosis.1?It has shown efficacy in multiple solid xenograft tumors models1?and in clinical studies in patients with acute myeloid leukemia2. Volasertib has also been shown to potently inhibit BRD43?(Kd = 79 nM3, IC50’s bromodomains 1 and 2 of BRD4 = 300 and 770 nM respectively2).
• Uses: Volasertib (BI 6727) is a highly potent Polo-like kinase (PLK) inhibitor.

Technology Process of Volasertib

There total 17 articles about Volasertib 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: 66.0%

2-chloro-7-ethyl-7,8-dihydro-5-methyl-8-(1-methylethyl)-(7R)-6(5H)-pteridinone (877676-50-1) + 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide → N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide (755038-65-4)

Guidance literature:

2-chloro-7-ethyl-7,8-dihydro-5-methyl-8-(1-methylethyl)-(7R)-6(5H)-pteridinone; 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide; With toluene-4-sulfonic acid; In Methyl isobutyl carbinol; water; for 24h; Heating / reflux;

With sodium hydroxide; In Methyl isobutyl carbinol; dichloromethane; water; at 60 ℃; pH=9;

Reference yield:

N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)-6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide trihydrochloride trihydrate → N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide (755038-65-4)

Guidance literature:

With water; potassium carbonate; In Isopropyl acetate; at 50 ℃; for 1h; Product distribution / selectivity;

Reference yield:

N-(4-oxocyclohexyl)acetamide (27514-08-5) → N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide (755038-65-4)

Guidance literature:

Multi-step reaction with 5 steps

1.1: toluene / Reflux

1.2: 50 °C / 2585.81 Torr

2.1: water / 6 h / 120 °C / sealed tube

3.1: pyridine / toluene / Reflux

3.2: 1.5 h / Reflux

3.3: 2 h / 20 - 60 °C

4.1: hydrogen / Raney-Nickel / tetrahydrofuran; methanol / 60 °C / 2585.81 Torr

5.1: toluene-4-sulfonic acid / Methyl isobutyl carbinol / 22 h / Reflux

5.2: 2 h / Reflux

5.3: pH 9

With pyridine; hydrogen; toluene-4-sulfonic acid; Raney-Nickel; In tetrahydrofuran; methanol; Methyl isobutyl carbinol; water; toluene;

upstream raw materials:

2-chloro-7-ethyl-7,8-dihydro-5-methyl-8-(1-methylethyl)-(7R)-6(5H)-pteridinone

N-(4-oxocyclohexyl)acetamide

1-cyclopropylmethylpiperazine

(x)C₇H₈O₃S*C₁₄H₂₇N₃

Refernces

• 1、 -. "Process for manufacturing dihydropteridinones and intermediates thereof". . . Retrieved 2013/03/26.
• 2、 -. "Process for the manufacture of dihydropteridinones". Page/Page column 67. . Retrieved 2008/12/07.