Tipifarnib

Base Information

• Chemical Name: Tipifarnib
• CAS No.: 192185-72-1
• Molecular Formula: C₂₇H₂₂Cl₂N₄O
• Molecular Weight: 489.404
• Hs Code.: 2933790090
• European Community (EC) Number: 870-169-0
• UNII: MAT637500A
• DSSTox Substance ID: DTXSID5041140
• Nikkaji Number: J2.227.995E
• Wikipedia: Tipifarnib
• NCI Thesaurus Code: C1703
• Pharos Ligand ID: UPJHWDV1AA11
• Metabolomics Workbench ID: 149355
• ChEMBL ID: CHEMBL289228
• Mol file: 192185-72-1.mol

Synonyms:(R)-6-(amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone;2 (1H))-quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-,(+)-;R 115777;R-115777;R115777;tipifarnib;Zarnestra

Chemical Property of Tipifarnib

Chemical Property:

• Appearance/Colour: Off-white to pale beige solid
• Vapor Pressure: 1.94E-18mmHg at 25°C
• Melting Point: 211-213 °C (dec.)
• Refractive Index: 1.671
• Boiling Point: 681.725 °C at 760 mmHg
• PKA: 7.20±0.10(Predicted)
• Flash Point: 366.094 °C
• PSA: 65.84000
• Density: 1.334 g/cm³
• LogP: 6.19670
• Storage Temp.: -20?C Freezer
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 488.1170667
• Heavy Atom Count: 34
• Complexity: 785

Purity/Quality:

99% ^*data from raw suppliers

Tipifarnib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1C=NC=C1C(C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N
• Isomeric SMILES: CN1C=NC=C1[C@@](C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N
• Recent ClinicalTrials: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
• Recent EU Clinical Trials: The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)
• Uses: A farnesyltransferase inhibitor. Sensitizes human multiple myeloma cell to proteasome inhibition by blocking degradation of bortezomib(B675700)-induced aggresomes. Also shown to inhibit the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage when combined with rapamycin(R124000). A farnesyltransferase inhibitor. Sensitizes human multiple myeloma cell to proteasome inhibition by blocking degradation of bortezomib(B675700)-induced aggresomes. Also shown to inhibit the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage when combined with rapamycin(R124000).

Technology Process of Tipifarnib

There total 55 articles about Tipifarnib 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: 85.0%

(±)-4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy-(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone monohydrochloride → 6-[amino(4-chlorophenyl)-1-methyl-1H-imidazol-5-ylmethyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone (192185-68-5,192185-72-1)

Guidance literature:

(±)-4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy-(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone monohydrochloride; With thionyl chloride; at 20 - 45 ℃; for 3h;

With ammonia; In methanol; at 12 - 45 ℃; for 15h;

Reference yield: 83.0%

(S)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1H-quinolin-2-one (869217-40-3) + methyl iodide (74-88-4) → tiparfinib (192185-71-0,192185-72-1)

Guidance literature:

With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In tetrahydrofuran; water; at 20 ℃; for 2h;

Reference yield:

N-[(4-chlorophenyl)((4-(3-chlorophenyl)-1-methyl-1H-quinoline-2-one)-6-yl)(1-methyl-1H-imidazole-5-yl)methyl]-2-methyl-2-propanesulfinamide [S(R)] → tiparfinib (192185-71-0,192185-72-1) + tipifarnib (192185-72-1)

Guidance literature:

N-[(4-chlorophenyl)((4-(3-chlorophenyl)-1-methyl-1H-quinoline-2-one)-6-yl)(1-methyl-1H-imidazole-5-yl)methyl]-2-methyl-2-propanesulfinamide [S(R)]; With hydrogenchloride; methanol; water; isopropyl alcohol; at 20 ℃; for 0.5h;

With potassium carbonate; In methanol; water; isopropyl alcohol; at 0 ℃;

upstream raw materials:

3-chloro-benzeneacetonitrile

(4-Chlorophenyl)(4-nitrophenyl)methanone

(2-amino-5-bromo-phenyl)-(3-chloro-phenyl)-methanone

para-nitrophenyl bromide

Downstream raw materials:

4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone

Refernces

• 1、 -. "DIASTEREOSELECTIVE ADDITION OF LITHIATED N-METHYLIMIDAZOLE ON SULFINIMINES". Page/Page column 16. . Retrieved 2008/06/13.
• 2、 -. "DIASTEREOSELECTIVE SYNTHESIS PROCESS WITH 6-BROMO-4-(3-CHLOROPHENYL)-2-METHOXY-QUINOLINE". Page/Page column 18. . Retrieved 2008/06/13.