تفاعل #753

معادلة التفاعل

Cc1cc(Cl)ncc1-c1ccc(

C[C@H]1CNCCN1C

→

Cc1cc(N2CCN(C)[C@@H]

المردود 34.7%

المذيبات

C1COCCO1

ظروف التفاعل

الإجراء التجريبي

A mixture of CHLORO(2-DICYCLOHEXYLPHOSPHINO-2',6'-DI-I- PROPOXY-1,1'-BIPHENYL)[2-(2-AMINOETHYLPHENYL)]PALLADIUM(II), METHYL-T- BUTYLETHER ADDUCT (Ru Phos Pd cycle) (69.2 mgs, 0.2eq), sodium tert-butoxide (244 mg, 2.54 mmol) ,2-(4-(6-chloro-4-methylpyridin-3-yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (200 mg, 0.42 mmol) , (S)-1,2-dimethylpiperazine (198 mg, 1.06 mmol) in dioxane (20ml) was stirred at 115°C for 1hr, LCMS indicated the completion of reaction. The solid was filtered off through a pad of celite, washed with DCM. The solvent of the filtrate was removed by concentration, taken into 2ml of DMSO, purified with reverse phase chromatography column (eluted with 5% to 50% 0.1%TFA in ACN/0.1%TFA in water), the fractions were combined and lyphlized, to yield 117mgs of product. LCMS indicated 9% of TFA coupled side product. The solid was taken into 10ml sat. NaHCO3 aq, sonicated, until the disapearance of the side product, filtered, washed with water, dried to yield (S)-2-(4-(6-(3,4-dimethylpiperazin-1-yl)-4-methylpyridin-3-yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (67.0 mg, 34.7 %) as a yellow solid.

المصدر