2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(3-chloro-5-morpholinophenyl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431746Notes

Reaction equation

HRID 1431746 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[Cl:35][C:36]1[CH:37]=[C:38]([CH:40]=[C:41]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[CH:42]=1)[NH2:39].Cl[C:50]1[C:59]2[C:54](=[CH:55][C:56]([F:61])=[CH:57][C:58]=2[F:60])[N:53]=[C:52]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=2)[C:51]=1[CH3:68].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]>[Cl:35][C:36]1[CH:37]=[C:38]([NH:39][C:50]2[C:59]3[C:54](=[CH:55][C:56]([F:61])=[CH:57][C:58]=3[F:60])[N:53]=[C:52]([C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=3)[C:51]=2[CH3:68])[CH:40]=[C:41]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[CH:42]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596314003-Chloro-5-morpholinoaniline

Product 1

HCID 59631163N-(3-chloro-5-morpholinophenyl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled products were prepared according to Procedure S using of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.026 g, 0.055 mmol), 3-chloro-5-morpholinoaniline (0.088 g, 0.413 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.1 g, 0.344 mmol) and Pd2dba3 (0.013 g, 0.014 mmol) and sodium tert-butoxide (0.063 g, 0.66 mmol) in toluene (3.4 mL) at 100° C. for 45 mins. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes) to give the desired product N-(3-chloro-5-morpholinophenyl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.72 (1H, ddd, J=4.9, 1.8, 1.0 Hz), 7.89 (1H, td, J=7.4, 1.8 Hz), 7.80-7.85 (1H, m), 7.67 (1H, br. s.), 7.38 (1H, ddd, J=7.5, 4.8, 1.2 Hz), 7.02 (2H, ddd, J=13.7, 8.6, 2.5 Hz), 6.51 (1H, s), 6.36 (1H, s), 6.27 (1H, s), 3.83 (4H, app t, J=4.9 Hz), 3.15 (4H, app t, J=4.9 Hz), 2.17 (3H, s). Mass Spectrum (ESI) m/e=467.2 (M+1).

Workup

  1. customwere prepared
  2. customThe crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fcb70c8e318e4dee94cc73097e5ca0df
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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