Triethylamine → 6-fluoro-2-[(1S,5S)-6-(4-methoxyphenyl)-3,6-diazabicyclo[3.2.2]non-3-yl]quinazoline

Participants

Reaction Conditions

Reaction Steps

To a solution of (1S,5S)-6-(4-methoxyphenyl)-3,6-diazabicyclo[3.2.2]-nonan-2-one (E-4, 0.108 g, 0.438 mmol, 1.0 equiv) in THF (3.0 mL) at ambient temperature was added a solution of lithium aluminum hydride in THF (1.31 mL, 1.31 mmol, 1.0M, 3.0 equiv) and the reaction mixture was heated to 65° C. for 2 h. The reaction was cooled to 0° C. and quenched with water (0.1 mL), 1M NaOH (0.2 mL), and water (0.3 mL). The reaction mixture was stirred a further 0.5 h, diluted with ethyl acetate (50 mL), dried over MgSO4, and concentrated to an oil. To a solution of the residual oil in dimethylacetamide (2.1 mL) was added triethylamine (0.24 mL, 1.72 mmol, ca. 4 equiv), and 2-chloro-6-fluoroquinazoline (0.094 g, 0.52 mmol, ca. 1.2 equiv) and the reaction was heated to 175° C. for 15 minutes in the microwave. The reaction was cooled and partitioned between ethyl acetate and water. The organic phase was dried over MgSO4 and concentrated. The residue was purified by column chromatography (0 to 60% ethyl acetate in hexanes) to afford E-5 as a yellow solid. ESI MS [M+H] for C22H23FN4O=379.2.

Provenance & Evidence