Reaction #1726712

Reaction equation

4-piperidone

3-hydroxy-2-naphthalenecarboxamide

morpholine

→

Compound 159

spiro[2H-naphtho[2,3-e]-1,3-oxazin-2,4′-piperidin]-4-(3H)-one

Solvents

ethyl acetate

toluene

methanol

Conditions

Workup

1. 1
   Temperatureis refluxed for 20 hr
2. 2
   Washwashed with water, brine
3. 3
   Dryingdried over Na2SO4
4. 4
   OtherAfter solvent removal by rotoevaporation
5. 5
   Otherthe crude product is purified by preparative TLC

Procedure

A mixture of 26 mg (0.083 mmol) of N-[4,8-dimethoxyquinoline-2-yl)carbonyl]-4-piperidone (prepared as described in Example 44), 15.5 mg (0.083 mmol) of 3-hydroxy-2-naphthalenecarboxamide, and 0.020 mL of morpholine in a mixture of 0.2 mL of toluene and 0.6 mL of methanol is refluxed for 20 hr. The reaction mixture is diluted with ethyl acetate, and washed with water, brine, and dried over Na2SO4. After solvent removal by rotoevaporation, the crude product is purified by preparative TLC to give 11 mg (0.023 mmol, 27% yield) of 1′-[4,8-dimethoxyquinoline-2-yl)carbonyl]spiro[2H-naphtho[2,3-e]-1,3-oxazin-2,4′-piperidin]-4-(3H)-one (Compound 159): 1H NMR (DMSO-d6): δ 3.95 (s, 3H), 4.07 (s, 3H), 7.20 (s, 1H), 7.23 (d, 1H), 7.44 (d of d, 1H), 7.55 (m, 3H), 7.67 (d, 1H), 8.04 (d, 1H), 8.46 (s, 1H), and 9.09 ppm (s, 1H). MS m/z: 484.0 (M+H)+, 506.0 (M+Na)+.

Source