Triphenylphosphine → methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

Participants

Reaction Steps

DTAD (11.48 g, 49.9 mmol) was added portion-wise to an ice-cooled solution of 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol (7.36 g, 20 mmol), (S)-methyl lactate (2.29 ml, 24 mmol) and triphenylphosphine (13.1 g, 49.9 mmol) in DCM (200 ml). The mixture was stirred at room temperature for 1 hour. The mixture was extracted with 2N hydrochloric acid (2×50 ml). The hydrochloric layers were combined and washed with DCM. The pH of the solution was adjusted to pH 9 by slow addition of concentrated aqueous ammonia while cooling. This aqueous solution was extracted with DCM (2×100 ml). These DCM layers were combined, washed with water and brine and dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 4% methanol in DCM) to give methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate as a yellowish solid (7.35 g, 80%); NMR Spectrum (CDCl3) 1.80 (d, 3H), 3.85 (s, 3H), 5.15 (q, 1H), 5.76 (s, 2H), 6.79 (d, 1H), 6.85 (d, 1H), 7.18 (m, 1H), 7.43 (d, 1H), 7.50 (d, 1H), 7.63-7.54 (m, 2H), 7.70 (dd, 1H), 8.11 (s, 1H), 8.38 (s, 1H), 8.59 (br d, 1H), 8.63 (s, 1H); Mass spectrum MH+ 455.

Provenance & Evidence