ChemicalBook CAS DataBase List Regorafenib

Regorafenib synthesis

12synthesis methods

Product Name:Regorafenib
CAS Number:755037-03-7
Molecular formula:C21H15ClF4N4O3
Molecular Weight:482.82

Regorafenib, also known as BAY 73-4506 ; is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

Du, Fangyu; Zhou, Qifan; Shi, Yajie; Yu, Miao; Sun, Wenjiao; Chen, Guoliang. A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib. Synthetic Communications. Volume 49. Issue 4. Pages 576-586. Journal; Online Computer File. (2019).

757251-39-1 Synthesis

4-(4-AMINO-3-FLUOROPHENOXY)-N-METHYLPICOLINAMIDE

757251-39-1
234 suppliers
$11.00/250mg

42558-54-3 Synthesis

42558-54-3
382 suppliers
$10.00/5g

320-51-4 Synthesis

4-Chloro-alpha,alpha,alpha-trifluoro-m-toluidine

320-51-4
457 suppliers
$6.00/10g

755037-03-7
451 suppliers
$25.00/5 mg

Yield:755037-03-7 96.8%

Reaction Conditions:

with dmap in N,N-dimethyl-formamide at 140; for 4 h;Green chemistry;Temperature;

Steps:

8 Preparation of regomafenib (I)
To the reaction flask, a compound IV 13.27 g, a compound V 9.93 g, a methyl isobutyryl acetate 7.32 g, a 4-dimethylaminopyridine 6.21 g, and 800 ml of DMF were sequentially added, and the mixture was stirred and dissolved, and the temperature was controlled at 140 ° C for 4 h. The TLC monitors the completion of the reaction. The reaction was stopped, the temperature was lowered to room temperature, and ethyl acetate was added for extraction. The organic layer was separated and concentrated under reduced pressure to give 25.55 g, product yield 96.8%, purity 99.93%.

References:

Shandong Luoxin Pharmaceutical Group Hengxin Pharmaceutical Co., Ltd.;Liu Zhenteng;Hou Junkai;Fan Xuezhen;Yang Taotao CN108329260, 2018, A Location in patent:Paragraph 0014; 0037; 0040; 0043-0046

FullText

757251-39-1 Synthesis

757251-39-1
234 suppliers
$11.00/250mg

327-78-6 Synthesis