2-Chloroethyl isocyanate → N-(2-Chloroethyl)-N'-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)urea

Participants

Reaction Conditions

Reaction Steps

Chloroethylisocyanate (116 μl, 1.36 mmol) was added drop wise to an ice-cooled solution of 5-[(1R)-2-amino-1-methylethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (516 mg, 1.24 mmol, obtained as described in Example 112, preparation of starting materials) in DCM (10 ml). The mixture was stirred at 0° C. for 30 minutes and at room temperature for 1 hour. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 3% to 5% 7N ammonia-methanol in DCM) to give the title compound (584 mg, 74%); NMR Spectrum: (CDCl3) 1.46 (d, 3H), 2.28 (s, 3H), 2.52 (s, 3H), 3.46 (m, 1H), 3.57 (m, 4H), 4.00 (m, 1H), 4.76 (m, 1H), 6.40 (m, 1H), 6.62 (m, 1H), 6.67 (d, 1H), 6.91 (d, 1H), 7.08 (d, 1H), 7.12 (dd, 1H), 7.18 (d, 1H), 7.34 (t, 1H), 7.53 (dd, 1H), 7.67 (s, 1H), 8.27 (s, 1H), 8.34 (s, 1H), 9.82 (s, 1H); Mass spectrum: MH+ 521.

Provenance & Evidence