Sodium t-butoxide → HCID 59631267, compound

HRID 1431377Notes

Reaction equation

HRID 1431377 reaction equation
[F:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][N:3]=1.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([F:27])=[CH:23][C:24]=2[F:26])[N:19]=[C:18]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[C:17]=1[CH3:34].C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.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:26][C:24]1[CH:23]=[C:22]([F:27])[CH:21]=[C:20]2[C:25]=1[C:16]([NH:8][C:7]1[C:2]([F:1])=[N:3][CH:4]=[C:5]([N:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[CH:6]=1)=[C:17]([CH3:34])[C:18]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)=[N:19]2

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 59631315HCID 59631315, compoundHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 59631267HCID 59631267, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-fluoro-5-morpholinopyridin-3-amine (0.12 g, 0.60 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.261 g, 0.90 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.055 g, 0.060 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (0.058 g, 0.121 mmol), and sodium tert-butoxide (0.176 g, 1.83 mmol) in dry toluene (5.0 mL) was degassed by nitrogen. The mixture was heated to 90° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organics were combined and dried over anhydrous magnesium sulfate. After filtration and concentration the residue was purified on basic alumina (0-60% EtOAc in hexanes) to afford an light yellow solid as 5,7-difluoro-N-(2-fluoro-5-(4-morpholinyl)-3-pyridinyl)-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (500 MHz, CDCl3) δ ppm 8.71 (1H, d, J=4.6 Hz), 7.93 (2H, m), 7.70 (1H, m), 7.42 (1H, d, J=2.7 Hz), 7.32 (1H, m), 7.15 (1H, m), 7.01 (1H, m), 6.58 (1H, d, J=7.1 Hz), 3.88 (4H, m), 3.16 (4H, m), 2.23 (3H, s). Mass Spectrum ESI (pos.) m/e: 452.2 (M+H)+.

Workup

  1. customwas degassed by nitrogen
  2. temperaturethe reaction was cooled to rt
  3. additiontreated with water
  4. extractionAfter extracting twice with EtOAc
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration the residue
  7. customwas purified on basic alumina (0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-44927f8fc29842c1986a93d387082d92
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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