Dimethylformamide → HCID 50939344, compound

HRID 1618649Notes

Reaction equation

HRID 1618649 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]3[NH:13][CH2:14][C:15]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:10]3=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.CN(C=O)C.[H-].[Na+].Cl[C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:32]=[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:30]=1[CH3:45].ClC1C=CC2C(=CC=CC=2)N=1>CCOC(C)=O>[CH3:45][C:30]1[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[N:32][C:33]2[C:38]([C:29]=1[N:13]1[C:11]3[C:10](=[CH:9][CH:8]=[C:7]([N:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)[CH:12]=3)[C:15]3([CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:14]1)=[CH:37][CH:36]=[CH:35][CH:34]=2

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 119282-ChloroquinolineHCID 24758Sodium hydrideHCID 12378945HCID 12378945, compoundHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]

Product 1

HCID 50939344HCID 50939344, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Under a N2 atmosphere, 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (0.216 g, 0.788 mmol) was dissolved in DMF (2.00 mL, 26.0 mmol) and treated with sodium hydride (0.0208 g, 0.867 mmol). The reaction was allowed to stir at rt for 10 minutes and 4-chloro-3-methyl-2-phenylquinoline (0.100 g, 0.394 mmol) was added. The reaction was placed in a preheated oil bath at 140° C. for 6 h. LCMS showed no starting chloroquinoline remained. The reaction was diluted with EtOAc and washed with 2% sodium bicarbonate followed by brine. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography eluting with 40% to 60% EtOAc in hexane. The fractions that contained product were further purified by preparative reverse phase chromatography to afford 1-(3-methyl-2-phenyl-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]. Mass Spectrum (ESI) m/e=492.3 (M+1) 1H NMR (500 MHz, DMSO-d6) δ ppm 8.06-8.10 (1H, m), 7.80-7.84 (1H, m), 7.74 (1H, ddd, J=8.4, 6.8, 1.5 Hz), 7.64-7.69 (2H, m), 7.48-7.59 (4H, m), 7.11 (1H, d, J=8.3 Hz), 6.27 (1H, dd, J=8.3, 2.2 Hz), 5.58 (1H, d, J=2.2 Hz), 4.01 (1H, d, J=9.8 Hz), 3.83-3.97 (3H, m), 3.56-3.63 (4H, m), 3.48 (2H, tt, J=12.0, 2.1 Hz), 2.82-2.91 (4H, m), 2.22 (3H, s), 1.93-2.05 (2H, m), 1.82-1.88 (1H, m), 1.65-1.73 (1H, m)

Workup

  1. waitThe reaction was placed in a preheated oil bath at 140° C. for 6 h
  2. washwashed with 2% sodium bicarbonate
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by flash column chromatography
  7. washeluting with 40% to 60% EtOAc in hexane
  8. customwere further purified by preparative reverse phase chromatography

Sources & evidence

ORD record
ord-9004fc287b8047cc9a1b47626d4dcd79
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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