Diisopropylamine → 3-(2-chloro-phenyl)-6-fluoro-2-(2-hydroxy-2-pyridin-2-yl-vinyl)-3H-quinazolin-4-one

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (0.061 mL, 0.47 mmol) in tetrahydrofuran (2.7 mL) was chilled to -78° C. and butyllithium (0.134 mL, 0.34 mmol, 2.5 N in hexanes) was added dropwise. The solution was stirred 20 min and then a solution 3-(2-chloro-phenyl)-6-fluoro-2-methyl-3H-quinazolin-4-one (0.10 g, 0.35 mmol) in tetrahydrofuran (0.7 mL) was added dropwise. The solution became intense red and was stirred 30 min. In a separate vessel a solution of ethyl picolinate (0.491 mL, 3.6 mmol) in tetrahydrofuran (2 mL) was prepared and chilled to -78° C. The cold red anion solution was added to the cold ethyl picolinate solution via canula over a two minute period. The resulting mixture was stirred 30 minutes at -78° C. and then was allowed to warm to ambient temperature. The reaction was quenched with water. The mixture was repeatedly extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over magnesium sulfate and concentrated. The residue was triturated with ether/hexane and the yellow solid which formed was collected and dried to yield 0.054 g (40%) of 3-(2-chloro-phenyl)-6-fluoro-2-(2-hydroxy-2-pyridin-2-yl-vinyl)-3H-quinazolin-4-one which had: mp>250° C. 1H NMR (DMSOd) δ8.45 (d, J=5 Hz, 1 H), 7.97 (d, J=7 Hz, 1 H), 7.90 (dt, J=1, 8 Hz, 1 H), 7.88-7.58 (m, 7 H), 7.35 (sym m, 1 H), 5.80 (s, 1 H). Analysis calculated for C21H13ClFN3O2 : C, 64.05; H, 3.33; N, 10.67. Found: C, 64.16; H, 3.71; N, 10.72.

Provenance & Evidence