2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631343, compound

HRID 1431477Notes

Reaction equation

HRID 1431477 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:72]=[CH:71][C:70]([CH3:73])=[C:69]([CH3:74])[CH:68]=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]>[CH3:74][C:69]1[CH:68]=[C:67]([C:57]2[C:56]([CH3:75])=[C:55]([NH:47][C:46]3[C:41]([N:38]4[CH2:39][CH2:40][O:35][CH2:36][CH2:37]4)=[N:42][CH:43]=[C:44]([N:48]4[CH2:49][CH2:50][O:51][CH2:52][CH2:53]4)[CH:45]=3)[C:64]3[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=3[F:65])[N:58]=2)[CH:72]=[CH:71][C:70]=1[CH3:73]

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631278HCID 59631278, compound

Product 1

HCID 59631343HCID 59631343, 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 (0.022 g, 0.045 mmol), 2,5-dimorpholinopyridin-3-amine (0.090 g, 0.34 mmol), 4-chloro-2-(3,4-dimethylphenyl)-5,7-difluoro-3-methylquinoline (0.090 g, 0.283 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.068 g, 0.71 mmol) in toluene (2.8 mL) at 120° C. for 1 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 2-(3,4-dimethylphenyl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.71-7.68 (1H, br d, J=10.0 Hz), 7.63 (2H, m), 7.37 (1H, br s), 7.28 (2H, m), 6.98 (1H, ddd, J=13.3, 8.6, 2.5 Hz), 6.36 (1H, d, J=2.2 Hz), 3.92 (4H, m), 3.83 (4H, app t, J=4.3 Hz), 3.25 (4H, br. s), 3.06 (4H, app t, J=4.3 Hz), 2.36 (6H, s), 2.15 (3H, s). Mass Spectrum (ESI) m/e=546.3 (M+1)

Workup

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

Sources & evidence

ORD record
ord-3fe01bdeb620459abbf5e7626b30d90c
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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