Morpholine → 1'-(8-Chloro-2,3-dimethyl-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618709Notes

Reaction equation

HRID 1618709 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[C:16]([Cl:21])[CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([CH3:22])[C:12]=3[CH3:23])[CH2:9][C:8]3([CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:5]2=[N:6][CH:7]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:21][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:15]=1[N:14]=[C:13]([CH3:22])[C:12]([CH3:23])=[C:11]2[N:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[CH:3]=2)[C:8]2([CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH2:9]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672845186'-Bromo-1'-(8-chloro-2,3-dimethylquinolin-4-yl)-1',2,2',3,5,6-hexahydrospiro-[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672857241'-(8-Chloro-2,3-dimethyl-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure N by stirring 6′-bromo-1′-(8-chloro-2,3-dimethylquinolin-4-yl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]-pyridine] (25 mg, 0.054 mmol), morpholine (4.75 μL, 0.054 mmol), Pd2dba3 (5 mg, 5.4 μmol) and XPhos (5.2 mg, 10.9 μmol) in toluene (2.0 mL) at reflux for 14 h. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(8-chloro-2,3-dimethyl-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 7.78 (1H, dd, J=7.4, 1.4 Hz), 7.58-7.62 (2H, m), 7.32-7.36 (1H, m), 5.68 (1H, d, J=2.3 Hz), 4.11-4.20 (2H, m), 3.95-4.00 (1H, m), 3.85-3.91 (1H, m), 3.74 (4H, dd, J=5.3, 4.5 Hz), 3.52-3.62 (2H, m), 2.92-3.05 (4H, m), 2.84 (3H, s), 2.33-2.42 (2H, m), 2.31 (3H, s), 1.73-1.87 (2H, m). Mass Spectrum (ESI) m/e=465.2 (M+1).

Workup

  1. customPrepared
  2. temperatureat reflux for 14 h
  3. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-4211f054b6144ddabc3d4424f177c5ef
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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