2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631272, compound

HRID 1431514Notes

Reaction equation

HRID 1431514 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][CH:70]=[CH:71][C:72]=2[CH3:73])[C:56]=1[CH3:74].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][CH:70]=[CH:71][C:72]=4[CH3:73])[C:56]=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)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631331HCID 59631331, compound

Product 1

HCID 59631272HCID 59631272, 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 (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.104 g, 0.39 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-3-yl)quinoline (0.1 g, 0.33 mmol), Pd2dba3 (0.012 g, 0.013 mmol) and sodium tert-butoxide (0.079 g, 0.82 mmol) in toluene (3.3 mL) at 120° C. for 19 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-3-methyl-2-(4-methylpyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (1H, d, J=5.1 Hz), 8.48 (1H, br. s), 7.78 (1H, d, J=5.7 Hz), 7.65 (1H, m), 7.55 (1H, d, J=2.5 Hz), 7.51 (1H, ddd, J=13.3, 9.2, 2.5 Hz), 7.41 (1H, d, J=5.1 Hz), 6.34 (1H, s), 3.74 (1H, br. s), 3.65 (4H, app t, J=4.3 Hz), br. s.), 3.19 (2H, br. s), 2.96 (4H, app t, J=5.0 Hz), 2.2 (2H, br. s), 2.15 (3H, s), 1.87 (3H, s). Mass Spectrum (ESI) m/e=533.2 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 19 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-3d6997a657974551add7d07c37b62c4a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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