5-Methylsalicylamide

Synthesis

22717-57-3

39506-61-1

General Steps: 1. 500 mg (3.01 mmol) of methyl 2-hydroxy-5-methylbenzoate was dissolved in 2 mL of dioxane and 2 mL of 28% aqueous ammonium hydroxide was added. The reaction mixture was heated at 80°C for 20 hours and subsequently concentrated to dryness by rotary evaporation. The resulting light brown solid was ground with ether to remove the unreacted ester to give 480 mg (2.89 mmol, 96% yield) of pure 2-hydroxy-5-methylbenzamide. 2. 26 mg (0.083 mmol) of N-[4,8-dimethoxyquinolin-2-yl]carbonyl]-4-piperidinone (prepared as described in Example 44), 12.5 mg (0.083 mmol) of 2-hydroxy-5-methylbenzamide, and 0.020 mL of morpholine were dissolved in 2 mL of methanol and the reaction was carried out at reflux for 20 hours. After completion of the reaction, the mixture was diluted with ethyl acetate, washed sequentially with water and brine, and the organic layer was dried over anhydrous sodium sulfate. After the solvent was removed by rotary evaporation, the crude product was purified by preparative thin layer chromatography (TLC) to afford 20 mg (0.045 mmol, 54% yield) of 1'-[4,8-dimethoxyquinolin-2-yl)carbonyl]-6-methylspiro[2H-1,3-benzoxazin-2,4'-piperidin]-4-(3H)-one (compound 137). Identification data of compound 137: 1H NMR (DMSO-d6): δ 2.28 (s, 3H), 3.95 (s, 3H), 4.06 (s, 3H), 6.98 (d, 1H), 7.19 (s, 1H), 7.23 (d, 1H), 7.33 (d, 1H), 7.52 (d, 1H), 7.56 (d, 1H), 7.68 (d, 1H), 8.77 (s, 1H). MS m/z: 448.1 (M + H)+, 470.0 (M + Na)+.

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