2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 50906990, compound

HRID 1431355Notes

Reaction equation

HRID 1431355 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH2:47])=[CH:45][C:44]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1.Cl[C:55]1[C:64]2[C:59](=[CH:60][C:61]([O:66][CH3:67])=[C:62]([Cl:65])[CH:63]=2)[N:58]=[C:57]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][N:69]=2)[C:56]=1[CH3:74].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.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:65][C:62]1[CH:63]=[C:64]2[C:59](=[CH:60][C:61]=1[O:66][CH3:67])[N:58]=[C:57]([C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][N:69]=1)[C:56]([CH3:74])=[C:55]2[NH:47][C:46]1[C:41]([N:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[N:42][CH:43]=[C:44]([N:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)[CH:45]=1

Participants

8

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631212HCID 59631212, compound

Product 1

HCID 50906990HCID 50906990, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of X-Phos (0.024 g, 0.050 mmol), 2,5-dimorpholinopyridin-3-amine (0.099 g, 0.38 mmol), 4,6-dichloro-7-methoxy-3-methyl-2-(pyridin-2-yl)-quinoline (0.10 g, 0.31 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.011 g, 0.013 mmol) in toluene (3.13 mL) was added sodium t-butoxide (0.075 g, 0.78 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. The reaction was then cooled to rt and diluted with water (25 mL). The mixture was extracted with EtOAc (2×10 mL) and DCM (10 mL). The organic layers were combined and washed with brine (20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc) to give the desired product 6-chloro-N-(2,5-di-4-morpholinyl-3-pyridinyl)-7-methoxy-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.72-8.79 (1H, m), 7.80-7.96 (3H, m), 7.63 (2H, br s), 7.37-7.45 (1H, m), 7.27 (1H, m), 6.79 (1H, br. s.), 6.27 (1H, m), 4.06 (3H, s), 3.93 (4H, t, J=4.6 Hz), 3.71-3.81 (4H, m), 3.24 (4H, br. s.), 2.92-3.00 (4H, m), 2.35 (3H, s). Mass Spectrum (ESI) m/e=547.2 (M+1).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. extractionThe mixture was extracted with EtOAc (2×10 mL) and DCM (10 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc)

Sources & evidence

ORD record
ord-1eeb7ea4688c4caa8f2ca41acf5c1ed9
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…