Carbon tetrabromide → (2S)-4-Bromo-2-hydroxy-N-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)butanamide

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Reaction Steps

Triphenylphosphine (650 mg, 2.5 mmol) was added portion wise over 30 minutes to a solution of (2S)-2,4-dihydroxy-N-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)butanamide (856 mg, 1.65 mmol, obtained as described in Example 112) and carbon tetrabromide (658 mg, 2 mmol) in DCM (10 ml). The mixture was stirred overnight at room temperature. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 2% to 5% 7N ammonia-methanol in DCM) to give the title compound (712 mg, 74%) as a solid; NMR Spectrum: (CDCl3) 1.53 (d, 3H), 2.07 (m, 1H), 2.28 (s, 3H), 2.38 (m, 1H), 2.52 (s, 3H), 3.51 (t, 2H), 3.80-3.65 (m, 2H), 4.34 (dd, 1H), 4.95 (m, 1H), 6.90 (m, 2H), 7.09 (d, 1H), 7.14 (dd, 1H), 7.28 (m, 1H), 7.50 (m, 3H), 7.63 (s, 1H), 8.23 (s, 1H), 8.44 (s, 1H); Mass spectrum: MH+ 580, 582.

Provenance & Evidence