ChemicalBook CAS DataBase List Nintedanib

Nintedanib synthesis

7synthesis methods

Product Name:Nintedanib
CAS Number:656247-17-5
Molecular formula:C31H33N5O4
Molecular Weight:539.64

Nintedanib, also known as BIBF 1120, is an orally bioavailable inhibitor of vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet derived growth factor receptor (PDGFR). Intedanib selectively binds to and inhibits vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, which may result in the induction of endothelial cell apoptosis; a reduction in tumor vasculature; and the inhibition of tumor cell proliferation and migration.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

ROUTE 7

ROUTE 8

Roth, Gerald J.; Heckel, Armin; Colbatzky, Florian; Handschuh, Sandra; Kley, Jorg; Lehmann-Lintz, Thorsten; Lotz, Ralf; Tontsch-Grunt, Ulrike; Walter, Rainer; Hilberg, Frank. Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120). Journal of Medicinal Chemistry. Volume 52. Issue 14. Pages 4466-4480. Journal. (2009).

656247-18-6 Synthesis

656247-18-6
302 suppliers
$7.00/100mg

656247-17-5
368 suppliers
$5.00/10mg

Yield:656247-17-5 98.7%

Reaction Conditions:

with sodium hydrogencarbonate in water;ethyl acetate at 40; for 1 h;

Steps:

21 Example 21
A nintedanib dilauryl sulfate salt was prepared by the following general procedure: a. 15 g of nintedanib esylate was added to a co-solvent of ethyl acetate/l0% aqueous NaHC0₃ (450 ml/l50 ml) (30V/10V) and stirred at 40°C for 1 hour; (0326) b. The organic layer of the reaction mixture of step (a) was separated and washed twice with 150 mL of purified water (10V x 2); (0327) c. The organic extracts of step (b) were combined and concentrated to obtain nintedanib free base as a yellow powder (12.3 g, 98.7% yield)

References:

HANDA PHARMACEUTICALS, LLC;LIU, Fang-Yu;SUNG, K.C.;YANG, Chin-Yao;LIN, Chi-Cheng;LIN, Yi-Hsin;QIAO, Li WO2019/241504, 2019, A1 Location in patent:Page/Page column 74-75

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262368-30-9 Synthesis