Morpholine → 6-Methylspiro[2H-1,3-benzoxazine-2,4′-piperidin]-4(3H)-one

HRID 1639529Notes

Reaction equation

HRID 1639529 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.O[C:9]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12].N1CCOCC1>CO.C(OCC)(=O)C>[CH3:18][C:15]1[CH:16]=[CH:17][C:9]2[O:7][C:4]3([CH2:5][CH2:6][NH:1][CH2:2][CH2:3]3)[NH:13][C:11](=[O:12])[C:10]=2[CH:14]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 337214-PiperidoneHCID 107019875-MethylSalicylamide

Product 1

HCID 667226666-Methylspiro[2H-1,3-benzoxazine-2,4′-piperidin]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

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), 12.5 mg (0.083 mmol) of 2-hydroxy-5-methylbenzamide, and 0.020 mL of morpholine in 2 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 20 mg (0.045 mmol, 54% yield) of 1′-[4,8-dimethoxyquinoline-2-yl)carbonyl]-6-methylspiro-[2H-1,3-benzoxazin-2,4′-piperidin]-4-(3H)-one (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 of d, 1H), 7.33 (d of d, 1H), 7.52 (d of d, 1H), 7.56 (d, 1H), 7.68 (d of d, 1H), and 8.77 ppm (s, 1H). MS m/z: 448.1 (M+H)+, 470.0 (M+Na)+.

Workup

  1. temperatureis refluxed for 20 hr
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. customAfter solvent removal by rotoevaporation
  5. customthe crude product is purified by preparative TLC

Sources & evidence

ORD record
ord-087b3c62b7454b1ba7e430bc3da69298
Source dataset
uspto-grants-2012_02
Patent number
US08110570B2

Reaction notes

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