2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631579, compound

HRID 1431416Notes

Reaction equation

HRID 1431416 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.[C:54]([C:58]1[CH:63]=[CH:62][C:61]([C:64]2[C:73]([CH3:74])=[C:72](Cl)[C:71]3[C:66](=[CH:67][C:68]([F:77])=[CH:69][C:70]=3[F:76])[N:65]=2)=[CH:60][CH:59]=1)([CH3:57])([CH3:56])[CH3:55].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:72]3[C:71]4[C:66](=[CH:67][C:68]([F:77])=[CH:69][C:70]=4[F:76])[N:65]=[C:64]([C:61]4[CH:62]=[CH:63][C:58]([C:54]([CH3:56])([CH3:55])[CH3:57])=[CH:59][CH:60]=4)[C:73]=3[CH3:74])=[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 59631246HCID 59631246, compound

Product 1

HCID 59631579HCID 59631579, 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 (0.022 g, 0.046 mmol), 2,5-dimorpholinopyridin-3-amine (0.092 g, 0.35 mmol), 2-(4-tert-butylphenyl)-4-chloro-5,7-difluoro-3-methylquinoline (0.1 g, 0.29 mmol) and Pd2dba3 (10.6 mg, 0.012 mmol) in toluene (2.89 mL) was added sodium t-butoxide (0.069 g, 0.72 mmol). The reaction mixture was heated to 120° C. and stirring continued for 1.5 h. The reaction was cooled to rt and diluted with water (15 mL). The mixture was extracted with EtOAc (2×15 mL) and DCM (1×15 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(4-(2-methyl-2-propanyl)phenyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 7.59-7.73 (3H, m), 7.50-7.57 (4H, m), 6.98 (1H, m), 6.37 (1H, br. s.), 3.92 (4H, br. s.), 3.79-3.87 (4H, m), 3.25 (4H, br. s.), 2.99-3.09 (4H, m), 2.18 (3H, s), 1.36-1.45 (9H, s). Mass Spectrum (ESI) m/e=574.3 (M+1).

Workup

  1. temperatureThe reaction was cooled to rt
  2. extractionThe mixture was extracted with EtOAc (2×15 mL) and DCM (1×15 mL)
  3. washwashed with brine (1×20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-89b4cda4cbd14178ba24772f7ab5bc45
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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