Tandutinib

Base Information

• Chemical Name: Tandutinib
• CAS No.: 387867-13-2
• Molecular Formula: C₃₁H₄₂N₆O₄
• Molecular Weight: 562.712
• Hs Code.: 29154000
• NSC Number: 759851,726292
• UNII: E1IO3ICJ9A
• DSSTox Substance ID: DTXSID8048947
• Nikkaji Number: J2.069.102F
• Wikidata: Q27095683
• NCI Thesaurus Code: C48404
• Pharos Ligand ID: NQH2355ZLX3Q
• Metabolomics Workbench ID: 149486
• ChEMBL ID: CHEMBL124660
• Mol file: 387867-13-2.mol

Synonyms:4-(6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl)piperazine-1-carboxylic acid (4-isopropoxyphenyl)amide;CT 53518;CT-53518;CT53518;MLN 518;MLN-518;MLN518;tandutinib

Chemical Property of Tandutinib

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 1.35E-23mmHg at 25°C
• Melting Point: 177-178 °C
• Refractive Index: 1.61
• Boiling Point: 769.5 °C at 760 mmHg
• PKA: 13.39±0.70(Predicted)
• Flash Point: 419.2 °C
• PSA: 92.29000
• Density: 1.213 g/cm³
• LogP: 5.04830
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 10
• Exact Mass: 562.32675384
• Heavy Atom Count: 41
• Complexity: 783

Purity/Quality:

99% ^*data from raw suppliers

Tandutinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,N,Xi,F
• Hazard Codes: T,N,Xi,F

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)OC1=CC=C(C=C1)NC(=O)N2CCN(CC2)C3=NC=NC4=CC(=C(C=C43)OC)OCCCN5CCCCC5
• Recent ClinicalTrials: Tandutinib in Treating Patients Who Have Undergone Surgery for Metastatic Kidney Cancer
• Description: Tandutinib is a potent antagonist of platelet-derived growth factor receptor β (PDGFRβ), FLT3, and c-Kit (IC50 = 200, 220, and 170 nM, respectively). It less potently inhibits macrophage colony-stimulating factor 1 receptor (IC50 = 3.4 μM) and does not significantly inhibit other tyrosine or serine/threonine kinases. Tandutinib blocks the growth of cells expressing an internal tandem duplication within the juxtamembrane domain of the FLT3 receptor, found in some acute myelogenous leukemia cells. It also impairs the growth of colon cancer cells through its actions on the c-Kit receptor. Tandutinib reverses multidrug resistance in vitro by impairing the efflux activity of the multidrug resistance protein 7.
• Uses: An oral, small-molecule inhibitor of FLT3 for the treatment of AML (acute myelogenous leukemia) and other cancer indications. The drug exhibited limited activity as a single agent in phase I and II clinical trials in patients with AML and myelody antipsoratic An oral, small-molecule inhibitor of FLT3 for the treatment of AML (acute myelogenous leukemia) clinical trials in patients with AML and myelodysplastic syndrome, but displayed promising antileukemic activity (90% complete remissions) in a phase I/II trial in patients with newly diagnosed AML w hen administered in combination with cytarabine and daunorubicin.

Technology Process of Tandutinib

There total 23 articles about Tandutinib 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: 90.0%

N-(4-isopropoxyphenyl)piperazine-1-carboxamide hydrochloride (399037-37-7) + 4-chloro-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazoline (288383-71-1) → Tandutinib (387867-13-2)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; In ethanol; for 21.9h; Industry scale;

Reference yield:

3-methoxy-4-hydroxybenzoic acid (121-34-6) → Tandutinib (387867-13-2)

Guidance literature:

Multi-step reaction with 11 steps

1.1: 96 percent / K₂CO₃ / dimethylformamide / 20 °C

2.1: 96.5 percent / HNO₃; AcOH / CH₂Cl₂ / 100 °C

3.1: 95 percent / SnCl₂*H₂O / ethyl acetate / 50 °C

4.1: 81 percent / HCOONH₄ / 4 h / 150 °C

5.1: 62 percent / SOCl₂ / dimethylformamide / 4 h / Heating

6.1: 81 percent / DIEA / tetrahydrofuran / 50 °C

7.1: 98 percent / H₂ / Pd(OH)2/C / ethanol / 2585.74 Torr

8.1: 81.9 percent / Cs₂CO₃ / dimethylformamide / 65 °C

9.1: 46.4 percent / Et₃N / dimethylformamide / 70 °C

10.1: HCl / dioxane / 1 h

11.1: Et₃N / tetrahydrofuran; CH₂Cl₂ / 0.5 h / 20 °C

11.2: 55 mg / Et₃N / tetrahydrofuran; CH₂Cl₂ / 20 °C

With hydrogenchloride; thionyl chloride; hydrogen; nitric acid; ammonium formate; potassium carbonate; caesium carbonate; acetic acid; triethylamine; N-ethyl-N,N-diisopropylamine; tin(ll) chloride; palladium dihydroxide; In tetrahydrofuran; 1,4-dioxane; ethanol; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;

DOI:10.1021/jm020143r

Reference yield:

4-benzyloxy-3-methoxybenzoic acid benzyl ester (91203-74-6) → Tandutinib (387867-13-2)

Guidance literature:

Multi-step reaction with 10 steps

1.1: 96.5 percent / HNO₃; AcOH / CH₂Cl₂ / 100 °C

2.1: 95 percent / SnCl₂*H₂O / ethyl acetate / 50 °C

3.1: 81 percent / HCOONH₄ / 4 h / 150 °C

4.1: 62 percent / SOCl₂ / dimethylformamide / 4 h / Heating

5.1: 81 percent / DIEA / tetrahydrofuran / 50 °C

6.1: 98 percent / H₂ / Pd(OH)2/C / ethanol / 2585.74 Torr

7.1: 81.9 percent / Cs₂CO₃ / dimethylformamide / 65 °C

8.1: 46.4 percent / Et₃N / dimethylformamide / 70 °C

9.1: HCl / dioxane / 1 h

10.1: Et₃N / tetrahydrofuran; CH₂Cl₂ / 0.5 h / 20 °C

10.2: 55 mg / Et₃N / tetrahydrofuran; CH₂Cl₂ / 20 °C

With hydrogenchloride; thionyl chloride; hydrogen; nitric acid; ammonium formate; caesium carbonate; acetic acid; triethylamine; N-ethyl-N,N-diisopropylamine; tin(ll) chloride; palladium dihydroxide; In tetrahydrofuran; 1,4-dioxane; ethanol; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;

DOI:10.1021/jm020143r

upstream raw materials:

di(succinimido) carbonate

4-(isopropoxy)aniline

6-methoxy-4-(piperazin-1-yl)-7-(3-(piperidin-1-yl)propoxy)quinazoline

N-(4-isopropoxyphenyl)piperazine-1-carboxamide

Refernces

• 1、 -. "LACTATE SALT OF 4-(6-METHOXY-7-(3-PIPERIDIN-1-YL-PROPOXY)QUINAZOLIN-4-YL]PIPERAZINE-1-CARBOXYLIC ACID(4-ISOPROPOXYPHENYL)-AMIDE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CANCER AND OTHER DISEASES OR DISORDERS". Page/Page column 43. . Retrieved 2010/07/10.
• 2、 Pandey, Anjali,Volkots, Deborah L.,Seroogy, Joseph M.,Rose, Jack W.,Yu, Jin-Chen,Lambing, Joseph L.,Hutchaleelaha, Athiwat,Hollenbach, Stanley J.,Abe, Keith,Giese, Neill A.,Scarborough, Robert M.. "Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family". . p. 3772 - 3793. Retrieved 2007/10/03.