Triethylamine → 6-(6-Methylamino-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 41 mg (0.138 mMol) of triphosgene in 5 ml of CH2Cl2 is cooled to 2° C. Then a solution of 123 mg (0.41 mMol) of 3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-aniline and 82 μl (0.59 mMol) Et3N in 2 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 100 mg (0.39 mMol) of 6-methylamino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine (Step 3.2) and 54 μl (0.39 mMol) Et3N in 2 ml of CH2Cl2 is added during 5 min and stirring continued for 2 h at rt. EtOAc and a sat. 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 (Combi Flash; EtOAc/EtOH/Et3N 95:5:0→90:10→90:10:1) gives the title compound: MS: [M+1]+=584; TLC(EtOAc/EtOH/NH3conc. 90:10:1): Rf=0.11; HPLC: AtRet=10.1.

Provenance & Evidence