2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 50906787, compound

HRID 1431335Notes

Reaction equation

HRID 1431335 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[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](=[C:60]([C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][N:66]=3)[CH:61]=[CH:62][CH:63]=2)[N:58]=[C:57]([C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][N:72]=2)[C:56]=1[CH3:77].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]>[N:38]1([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[C:60]([C:65]5[CH:70]=[CH:69][CH:68]=[CH:67][N:66]=5)[CH:61]=[CH:62][CH:63]=4)[N:58]=[C:57]([C:71]4[CH:76]=[CH:75][CH:74]=[CH:73][N:72]=4)[C:56]=3[CH3:77])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:39][CH2:40][O:35][CH2:36][CH2:37]1

Participants

8

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631221HCID 59631221, compound

Product 1

HCID 50906787HCID 50906787, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.019 g, 0.040 mmol), 2,5-dimorpholinopyridin-3-amine (0.078 g, 0.30 mmol), 4-chloro-3-methyl-2,8-di(pyridin-2-yl)quinoline (0.082 g, 0.25 mmol) and Pd2dba3 (9.05 mg, 9.89 μmol) in toluene (2.5 mL) was added sodium t-butoxide (0.059 g, 0.62 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 (10 mL). The mixture was extracted with EtOAc (3×10 mL) and DCM (10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on basic alumina (0 to 100% EtOAc/DCM) to give the desired product N-(2,5-di-4-morpholinyl-3-pyridinyl)-3-methyl-2,8-di-2-pyridinyl-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.75-8.84 (1H, m), 8.69 (1H, br m), 8.28 (1H, d, J=7.6 Hz), 8.21 (1H, d, J=7.6 Hz), 7.97 (1H, d, J=7.6 Hz), 7.84 (2H, br. m.), 7.78 (1 h, m), 7.62 (2H, dd, J=16.0, 7.8 Hz), 7.28-7.35 (2H, br. m.), 6.82 (1H, br. s.), 6.25 (1H, br. s.), 3.95 (4H, br. s.), 3.73 (4H, br. s.), 3.27 (4H, br. s.), 2.93 (4H, br. s.), 2.52 (3H, s). Mass Spectrum (ESI) m/e=560.2 (M+1).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. extractionThe mixture was extracted with EtOAc (3×10 mL) and DCM (10 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography on basic alumina (0 to 100% EtOAc/DCM)

Sources & evidence

ORD record
ord-49dca8e5b6ed42dbab3bc0e2fd5e6131
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…