Morpholine → 1'-[7-Fluoro-3-Methyl-2-(Pyridin-2-Yl)quinolin-4-Yl]-6'-(Morpholin-4-Yl)-1',2,2',3,5,6-Hexahydrospiro[pyran-4,3'-Pyrrolo[3,2-B]pyridine]

HRID 1618524Notes

Reaction equation

HRID 1618524 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[CH2:9][C:8]3([CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:5]2=[N:6][CH:7]=1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.CC(C)([O-])C.[Na+].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]>[F:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([N:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH:3]=4)[C:8]4([CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)[CH2:9]3)=[C:12]([CH3:28])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[N:14]2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672853616'-Bromo-1'-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 509390781'-[7-Fluoro-3-Methyl-2-(Pyridin-2-Yl)quinolin-4-Yl]-6'-(Morpholin-4-Yl)-1',2,2',3,5,6-Hexahydrospiro[pyran-4,3'-Pyrrolo[3,2-B]pyridine]

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Prepared according to procedure N using 6′-bromo-1′-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (30 mg, 0.059 mmol), Pd2dba3 (5.4 mg, 5.94 μmol), morpholine (5.69 μL, 0.065 mmol), sodium tert-butoxide (11.4 mg, 0.119 mmol) and XPhos (5.66 mg, 0.012 mmol) in toluene (1.5 mL) and heating in the microwave for 1 h at 120° C. After purification 1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] was obtained as a yellow film. 1H NMR (400 MHz, chloroform-d) δ ppm 8.75 (1H, dd, J=3.3, 1.0 Hz), 7.83-7.97 (3H, m), 7.75 (1H, dd, J=9.2, 6.1 Hz), 7.62 (1H, d, J=2.3 Hz), 7.41 (1H, ddd, J=7.0, 5.1, 2.0 Hz), 7.28-7.34 (1H, m), 5.83 (1H, d, J=2.3 Hz), 4.09-4.23 (2H, m), 3.95-4.04 (2H, m), 3.71-3.80 (4H, m), 3.52-3.62 (2H, m), 3.01 (4H, q, J=4.4 Hz), 2.32-2.46 (5H, m), 1.74-1.91 (2H, m). Mass Spectrum (ESI) m/e=512 (M+1).

Workup

  1. customPrepared
  2. customAfter purification 1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]
  3. customwas obtained as a yellow film

Sources & evidence

ORD record
ord-9cfb2360901d41349a5b8cbe362f673e
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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