ChemicalBook CAS DataBase List Toceranib

Toceranib synthesis

5synthesis methods

Product Name:Toceranib
CAS Number:356068-94-5
Molecular formula:C22H25FN4O2
Molecular Weight:396.46

7154-73-6

5-((Z)-(5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

356068-93-4

356068-94-5

General procedure: 5-((Z)-(5-fluoro-2-oxoindolidine-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 g) was dissolved in dimethylformamide (500 ml), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (221 g), N-(2-aminoethyl)pyrrole (45.6 g) and triethylamine (93 ml). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solid product was collected by vacuum filtration and washed with ethanol. The resulting solid was slurried in ethanol (500 ml) by stirring at 64 °C for 1 h and subsequently cooled to room temperature. The solid was again collected by vacuum filtration, washed with ethanol and dried under vacuum to afford (Z)-5-((5-fluoro-2-oxoindol-3-ylidene)methyl)-2,4-dimethyl-N-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrrole-3-carboxamide (101.5 g, 77% yield). The product was characterized by 1H-NMR (dimethylsulfoxide-d6): δ 1.60 (m, 4H, 2xCH2), 2.40,2.44 (2xs, 6H, 2xCH3), 2.50 (m, 4H, 2xCH2), 2.57,3.35 (2xm, 4H, 2xCH2), 7.53,7.70,7.73,7.76 (4 xm. 4H, aromatic and vinyl), 10.88 (s, 1H, CONH), 13.67 (s, 1H, pyrrole NH). Mass spectral analysis showed m/z 396 [M + 1].

7154-73-6 Synthesis

7154-73-6
225 suppliers
$15.00/1g

356068-93-4 Synthesis

356068-93-4
142 suppliers
$45.00/25mg

356068-94-5
121 suppliers
$28.00/1mg

Yield: 77%

Reaction Conditions:

with (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate;triethylamine in DMF (N,N-dimethyl-formamide) at 20; for 2 h;

Steps:

5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 g) and dimethylformamide (500 ml) were stirred and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (221 g), 1-(2-aminoethyl) pyrrolidine (45.6 g) and triethylamine (93 ml) were added. The mixture was stirred for 2 hours at ambient temperature. The solid product was collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by stirring in ethanol (500 ml) for one hour at 64 C and cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol, and dried under vacuum to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol- (3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (101.5 g, 77 % yield). 1H-NMR (dimethylsulfoxide-d6) δ 1.60 (m, 4H, 2xCH2), 2.40, 2.44 (2xs, 6H, 2xCH3), 2.50 (m, 4H, 2xCH2), 2.57, 3.35 (2xm, 4H, 2XCH2), 7.53, 7.70, 7.73, 7.76 (4xm, 4H, aromatic and vinyl), 10.88 (s, 1H, CONH), 13.67 (s, 1H, pyrrole NH). MS m/z 396 [M+1].

References:

PHARMACIA & UPJOHN COMPANY WO2004/76410, 2004, A2 Location in patent:Page 12

253870-02-9 Synthesis