Triethylamine → 6-(6-Amino-pyrimidin-4-yloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid [3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-phenyl]-amide

Participants

Reaction Conditions

Reaction Steps

A solution of 83 mg (0.28 mMol) of triphosgene in 10 ml of CH2Cl2 is cooled to 2° C. Then a solution of 260 mg (0.86 mMol) of 3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-aniline and 171 μl (1-23 mMol) Et3N in 4 ml CH2Cl2 is added during 5 min. The mixture is stirred for 3 min at 2° C. and then warmed up to rt in a water bath. A solution of 200 mg (0.82 mMol) of 6-amino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine (Step 1.3) and 114 μl (0.82 mMol) Et3N in 4 ml of CH2Cl2 is added during 5 min and stirring continued for 2 h at rt. EtOAc and a diluted solution of Na2CO3 is added to the reaction mixture. The aqueous phase is separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; EtOAc/EtOH/Et3N 90:10:0→90:10:1) gives the title compound: TLC(EtOAc/EtOH/Et3N 90:10:1): Rf=0.15; MS: [M+1]+=570; Anal.: C,H,N,F.

Provenance & Evidence