Phosgene → HCID 58659451, compound

Participants

Reaction Steps

To an ice-cold solution of 4-(6-chloro-pyrimidin-4-yl-oxy)-aniline (Stage 21.1; 0.926 g, 4.18 mmol) and NEt3 (0.64 ml, 4.6 mmol) in CH2Cl2 (30 ml) under N2-atmosphere, phosgene (2.32 ml of a 20% solution in toluene, 4.39 mmol) in CH2Cl2 (10 ml) is added dropwise. The resulting suspension is stirred for 1 h, then filtered under exclusion of moisture and the filtrate concentrated in vacuo. THF (20 ml) and NEt3 (0.64 ml, 4.6 mmol) is then added to the residue. After cooling in an ice bath, 3-(4-ethyl-piperazin-1-ylmethyl)-5-trifluoromethyl-phenylamine (1.00 g, 3.48 mmol) dissolved in THF (20 ml) is added dropwise and the reaction mixture stirred for 30 min at 0° C. and 2 h at rt. Then it is diluted with water and AcOEt, the aqueous layer separated off and extracted twice with AcOEt. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; AcOEt/EtOH/Et3N 90:10:2→80:20:2) and crystallization from ether affords the title compound: m.p.: 168-169° C.; MS: [M+1]+=535; 1H-NMR (CD3OD): 8.54 (s, 1H), 7.82 (s, 1H), 7.60 (s, 1H), 7.54 (d, 2H), 7.30 (s, 1H), 7.14 (d, 2H), 7.09 (s, 1H), 3.60 (s, 2H), 2.57 (m, 8H), 2.47 (q, 2H), 1.12 (t, 3H).

Provenance & Evidence