Nitrogen → [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(5-phenylsulfanylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-amine

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Reaction Steps

A solution of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine 1D (1.0 g, 4.1 mmol) in DCM (60 ml) was sparged with N2 for 0.5 hr and then placed in a −20° C. bath. Thiophenol (0.42 ml, 4.1 mmol) and diisopropylethylamine (0.713 ml, 4.1 mmol) were added and the reaction was kept at −20° C. for 3 hr. After warming to rt, the reaction mixture was washed with water, dried (Na2SO4), and the solvent was removed. 1,2-Dichloroethane (20 ml), n-butanol (20 ml) and 3-chloro-4-(3-fluoro-benzyloxy)-phenylamine 3A (900 mg, 3.6 mmol) were added to the residue and the mixture was heated at 85° C. for 2.5 hr. The solvents were removed and the residue was taken up in DCM, washed with sat. aq. NaHCO3 solution and dried (Na2SO4). Removal of the solvent followed by chromatography on silica gel using DCM containing 0 to 5% MeOH as eluent afforded 7A (0.90 g, 50%) as a foam. LC/MS M++1=491; 1H-NMR (CDCl3):δ 4.51 (s, 2H), 5.15 (s, 2H), 6.52 (d, 1H, J=3 Hz), 6.93 (d, 1H, J=9 Hz), 7.02–7.49 (m, 11H), 7.80 (m, 1H, J=3 Hz), 8.18 (s, 1H), 8.74 (s, 1H).

Provenance & Evidence