2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 8-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431339Notes

Reaction equation

HRID 1431339 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]([Cl:65])[CH:61]=[CH:62][CH:63]=2)[N:58]=[C:57]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][N:67]=2)[C:56]=1[CH3:72].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:60]1[CH:61]=[CH:62][CH:63]=[C:64]2[C:59]=1[N:58]=[C:57]([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][N:67]=1)[C:56]([CH3:72])=[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 596310354,8-Dichloro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596310462,5-Dimorpholinopyridin-3-amine

Product 1

HCID 596314868-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

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 (0.026 g, 0.055 mmol), 2,5-dimorpholinopyridin-3-amine (0.110 g, 0.415 mmol), 4,8-dichloro-3-methyl-2-(pyridin-2-yl)quinoline (0.10 g, 0.35 mmol) and Pd2dba3 (0.013 g, 0.014 mmol) in toluene (3.46 mL) was added sodium t-butoxide (0.083 g, 0.865 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. After which the reaction was cooled to rt and diluted with water (25 mL). The mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 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 50% EtOAc/hexane) to give the desired product 8-chloro-N-(2,5-di-4-morpholinyl-3-pyridinyl)-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.71 (1H, d, J=4.3 Hz), 8.15 (1H, d, J=7.8 Hz), 7.93 (1H, m), 7.82 (1H, d, J=7.4 Hz), 7.76 (1H, br. s.), 7.60 (1H, d, J=2.5 Hz), 7.34-7.47 (2H, m), 6.79 (1H, br. s.), 6.21 (1H, br. s.), 3.93 (4H, br. s.), 3.67-3.79 (4H, m), 3.25 (4H, br. s.), 2.93 (4H, br. s.), 2.49 (3H, s). Mass Spectrum (ESI) m/e=517.2 (M+1).

Workup

  1. temperatureAfter which the reaction was cooled to rt
  2. extractionThe mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 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 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-164ea7213f6640a2b4e03a6b89c898c5
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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