Sodium Bicarbonate → 2-[(4-(5-Fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl]-2,3-dihydro[1,4]dioxino[2,3-f]quinazoline

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Reaction Steps

(2R)-2,3-Dihydro-1,4-dioxino[2,3-f]quinazolin-2-ylmethyl-4-methylbenzenesulfonate (800 mg, 3.7 mmole) was dissolved in a mixture of DMF/THF 1:1 v/v (30 mL) and 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (800 mg, 4 mmole) added, followed by the addition of sodium bicarbonate (1.0 gm, 9.4 mmole) and the mixture was refluxed under nitrogen for 18 hours. The solvent was evaporated under vacuum and the residue partitioned between methylene chloride and water. The organic phase was separated, washed with water and saturated sodium chloride solution, dried over magnesium sulfate and evaporated to a foam. Treatment of this foam with 3% methanol in chloroform yielded 320 mg (35%) of the (S)-enantiomer of the title compound as a yellow crystalline hemihydrate, m.p. 233-235° C.

Provenance & Evidence