ChemicalBook CAS DataBase List CEP-32496 (free base)

CEP-32496 (free base) synthesis

8synthesis methods

Product Name:CEP-32496 (free base)
CAS Number:1188910-76-0
Molecular formula:C24H22F3N5O5
Molecular Weight:517.46

3-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline

1188908-37-3

[5-(2,2,2-TRIFLUORO-1,1-DIMETHYL-ETHYL)-ISOXAZOL-3-YL]-CARBAMIC ACID PHENYL ESTER

1188911-77-4

1188910-76-0

A 10L Chemglass jacketed reactor, equipped with an N2 inlet/outlet, was charged with 3-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (Compound 2, 200.0 g, 637 mmol) and phenyl (5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)carbamate (Compound 3, 177.0 g, 596 mmol). equipped with N2 inlet/outlet, 4-dimethylaminopyridine (DMAP, 2.88 g) and 4.0 L of isopropylacetic acid were added. The internal temperature of the reaction mixture was raised to 70 °C and maintained at this temperature for 9 hours. The slurry was maintained during the reaction and HPLC monitoring showed that compound 2 was completely consumed after a period of heating. Subsequently, 2.0 L of heptane was added at 70 °C and the reaction mixture was cooled to 20 °C. Stirring was continued for 1 h to precipitate the solid, filtered, and the filter cake was washed with 2.0 L of a 1:1 (v/v) isopropyl acetate/heptane solvent mixture. The resulting white solid was dried under vacuum at 55 °C and 75 mbar by N2 exhaust to give 295 g (96% yield) of form A0 product with 99.3% HPLC purity.

1188908-37-3
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1188911-77-4 Synthesis

1188911-77-4
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1188910-76-0
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Yield: 96%

Reaction Conditions:

with dmap in Isopropyl acetate at 70; for 9 h;Inert atmosphere;

Steps:

Preparation from Form A₀
To a 10 L Chemglass jacketed reactor with N2 inlet/outlet was added compound 2 (200.0 g, 637 mmol), compound 3 (177.0 g, 596 mmol) and 4-Dimethylaminopyridine (DMAP) (2.88 g) followed by 4.0 L of isopropyl acetate. The internal temperature was raised to 70°C and heated for 9 hours. The reaction remained a slurry throughout there action and HPLC showed no compound 2 remaining after heating for that period. Next,2.0 L of heptane were added at 70°C and the reaction cooled to 20°C. The solids were stirred for lhour, filtered and the cake washed with 2.0 L of 1:1 isopropyl acetate/ heptanes. The white solids were placed in an oven with N2 bleed at 55°C under 75 mbar vacuum. The resulting solids weighed 295 g (96% yield) of Form A0 with 99.3 % purity by HPLC.

References:

CEPHALON, INC.;BIERLMAIER, Stephen J.;HALTIWANGER, Ralph C.;JACOBS, Martin J. WO2014/164648, 2014, A2 Location in patent:Paragraph 23

1188908-37-3
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