2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631350, compound

HRID 1431500Notes

Reaction equation

HRID 1431500 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](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:68]=[N:69][C:70]([O:73][CH3:74])=[CH:71][CH:72]=2)[C:56]=1[CH3:75].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]>[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:68]=[N:69][C:70]([O:73][CH3:74])=[CH:71][CH:72]=4)[C:56]=3[CH3:75])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631313HCID 59631313, compound

Product 1

HCID 59631350HCID 59631350, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.024 g, 0.050 mmol), 2,5-dimorpholinopyridin-3-amine (0.099 g, 0.37 mmol), 4-chloro-5,7-difluoro-2-(6-methoxypyridin-3-yl)-3-methylquinoline (0.1 g, 0.31 mmol), Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.075 g, 0.78 mmol) in toluene (3.1 mL) at 120° C. for 3.2 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-2-(6-methoxypyridin-3-yl)-3-methylquinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.45 (1H, d, J=2.4 Hz), 7.92 (1H, dd, J=8.5, 2.4 Hz), 7.72 (1H, br d, J=11.2 Hz), 7.66 (1H, d, J=2.5 Hz), 7.60 (1H, br d, J=8.0 Hz), 7.00 (1H, ddd, J=8.5, 0.7 Hz), 6.92 (1H, d, J=13.5, 8.6, 2.7 Hz), 6.35 (3H, d, J=2.3 Hz), 4.03 (3H, s), 3.91 (4H, t, J=4.7 Hz), 3.82 (4H, app t, J=4.7 Hz), 3.25 (4H, br. s.), 3.04 (4H, app t, J=4.9 Hz), 2.21 (3H, s). Mass Spectrum (ESI) m/e=549.3 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 3.2 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-525e2b6990b4409aa2070fd084a5616d
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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