Brivanib

Base Information

• Chemical Name: Brivanib
• CAS No.: 649735-46-6
• Molecular Formula: C19H19FN4O3
• Molecular Weight: 370.383
• Hs Code.: 2933990090
• European Community (EC) Number: 639-685-1
• UNII: DDU33B674I
• DSSTox Substance ID: DTXSID60215294
• Nikkaji Number: J2.765.119D
• Wikidata: Q27075503
• NCI Thesaurus Code: C67040
• Pharos Ligand ID: DU79TW278D4T
• Metabolomics Workbench ID: 153031
• ChEMBL ID: CHEMBL377300
• Mol file: 649735-46-6.mol

Synonyms:BMS 540215;BMS 582664;BMS-540215;BMS-582664;BMS540215;BMS582664;brivanib;brivanib alaninate

Chemical Property of Brivanib

Chemical Property:

• Refractive Index: 1.66
• PKA: 14.18±0.20(Predicted)
• PSA: 84.67000
• Density: 1.42 g/cm³
• LogP: 3.51840
• Solubility.: insoluble in H2O; ≥18.5 mg/mL in DMSO; ≥3.39 mg/mL in EtOH with ultrasonic
• XLogP3: 3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 370.14411864
• Heavy Atom Count: 27
• Complexity: 515

Purity/Quality:

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

Brivanib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OCC(C)O)C
• Isomeric SMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OC[C@@H](C)O)C
• Recent ClinicalTrials: Irinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF
• Recent EU Clinical Trials: A Blinded, Randomized, Phase 1/2 Study of Brivanib Alaninate vs. Placebo in Combination with Erbitux and Irinotecan in K-Ras wild type Subjects with Metastatic Colorectal Cancer.
• Uses: Brivanib is an ATP-competitive inhibitor against human VEGFR2 and FGFR with IC50 of 25 nM and 148 nM, respectively.

Technology Process of Brivanib

There total 10 articles about Brivanib 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: 81.0%

4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-ol (649735-41-1) + (R)-propylene oxide (15448-47-2) → Brivanib (649735-46-6)

Guidance literature:

With triethylamine; lithium chloride; In ethanol; at 70 ℃; for 3h;

DOI:10.1021/jm7013309

Reference yield:

C16H12FN4O2(1-)*Na(1+) + (R)-propylene oxide (15448-47-2) → Brivanib (649735-46-6)

Guidance literature:

In water; acetonitrile; at 28 ℃; for 20 - 24h;

Reference yield:

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) → Brivanib (649735-46-6)

Guidance literature:

Multi-step reaction with 3 steps

1.1: NaH / dimethylformamide / -78 - 20 °C

1.2: dimethylformamide / 1 h / 20 °C

2.1: 86 percent / HCOONH₄ / Pd/C / dimethylformamide / 1.5 h / 20 °C

3.1: 53 percent / Et₃N / ethanol / 2 h / 70 °C

With ammonium formate; sodium hydride; triethylamine; palladium on activated charcoal; In ethanol; N,N-dimethyl-formamide;

DOI:10.1021/jm051106d

upstream raw materials:

4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-ol

(R)-propylene oxide

4-fluoro-2-methyl-1H-indol-5-ol

4-Phenoxy-5-methyl-6-hydroxypyrrolo[2,1-f][1,2,4]triazine

Downstream raw materials:

(S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl) 2-(benzyloxycarbonylamino)propanoate

C₂₉H₂₈FN₅O₆

C₃₁H₃₂FN₅O₅

C₃₃H₃₆FN₅O₆

Refernces

• 1、 Cai, Zhen-Wei,Zhang, Yongzheng,Borzilleri, Robert M.,Qian, Ligang,Barbosa, Stephanie,Wei, Donna,Zheng, Xiaoping,Wu, Lawrence,Fan, Junying,Shi, Zhongping,Wautlet, Barri S.,Mortillo, Steve,Jeyaseelan Sr., Robert,Kukral, Daniel W.,Kamath, Amrita,Marathe, Punit,D'Arienzo, Celia,Derbin, George,Barrish, Joel C.,Robl, Jeffrey A.,Hunt, John T.,Lombardo, Louis J.,Fargnoli, Joseph,Bhide, Rajeev S.. "Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol- 5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl) 2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth ". . p. 1976 - 1980. Retrieved 2008/12/22.
• 2、 Bhide, Rajeev S.,Cai, Zhen-Wei,Zhang, Yong-Zheng,Qian, Ligang,Wei, Donna,Barbosa, Stephanie,Lombarde, Louis J.,Borzilleri, Robert M.,Zheng, Xiaoping,Wu, Laurence I.,Barrish, Joel C.,Kim, Soong-Hoon,Leavitt, Kenneth,Mathur, Arvind,Leith, Leslie,Chao, Sam,Wautlet, Barri,Mortillo, Steven,Jeyaseelan Sr., Robert,Kukral, Daniel,Hunt, John T.,Kamath, Amrita,Fura, Aberra,Vyas, Viral,Marathe, Punit,D'Arienzo, Celia,Derbin, George,Fargnoli, Joseph. "Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol- 5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor". . p. 2143 - 2146. Retrieved 2007/10/03.