Morpholine → 2-((7-Fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)-4-(4-morpholinyl)benzonitrile

HRID 1431266Notes

Reaction equation

HRID 1431266 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:12]=2[CH3:28])[CH:3]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:63]1[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1.CC(C)([O-])C.[Na+]>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]([O:10][C:4]3[CH:3]=[C:2]([N:63]4[CH2:68][CH2:67][O:66][CH2:65][CH2:64]4)[CH:9]=[CH:8][C:5]=3[C:6]#[N:7])=[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 596310624-Bromo-2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)benzonitrile

Product 1

HCID 596315372-((7-Fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)-4-(4-morpholinyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to general Procedure H using 4-bromo-2-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yloxy)benzonitrile (70 mg, 0.16 mmol), tris(dibenzylideneacetone)dipalladium(0) (7.4 mg, 0.008 mmol), X-Phos (7.7 mg, 0.016 mmol), morpholine (28 mg, 0.32 mmol) and sodium tert-butoxide (31 mg, 0.32 mmol) in toluene (6.9 mL) and heating at reflux for 2 h. After purification 2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)-4-(4-morpholinyl)benzonitrile was obtained. 1H NMR (400 MHz, chloroform-d) δ ppm 8.68-8.78 (1H, m), 7.86-7.95 (3H, m), 7.82 (1H, dd, J=10.0, 2.5 Hz), 7.57 (1H, d, J=8.6 Hz), 7.41 (1H, ddd, J=6.7, 4.6, 2.3 Hz), 7.30-7.36 (1H, m), 6.56 (1H, dd, J=9.0, 2.3 Hz), 5.83 (1H, d, J=2.3 Hz), 3.69 (4H, dd, J=6.1, 3.7 Hz), 2.90-3.10 (4H, m), 2.30-2.46 (3H, s). Mass Spectrum (ESI) m/e=441.0 (M+1).

Workup

  1. customPrepared
  2. temperatureheating
  3. temperatureat reflux for 2 h
  4. customAfter purification 2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)-4-(4-morpholinyl)benzonitrile
  5. customwas obtained

Sources & evidence

ORD record
ord-220183b6a2624691b348b2f2e518f19c
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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