Morpholine → HCID 66723749, compound

HRID 1639530Notes

Reaction equation

HRID 1639530 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.O[C:9]1[C:10]([C:19]([NH2:21])=[O:20])=[CH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2.N1CCOCC1>C1(C)C=CC=CC=1.CO.C(OCC)(=O)C>[NH:1]1[CH2:6][CH2:5][C:4]2([NH:21][C:19](=[O:20])[C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][C:9]=3[O:7]2)[CH:16]=[CH:15][CH:14]=[CH:13]4)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 193172-Naphthalenecarboxamide, 3-hydroxy-HCID 337214-Piperidone

Product 1

HCID 66723749HCID 66723749, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 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), 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)+.

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-e18c9eaa04fa475abf3e7ca4c3afc891
Source dataset
uspto-grants-2012_02
Patent number
US08110570B2

Reaction notes

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