2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631093, compound

HRID 1431469Notes

Reaction equation

HRID 1431469 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](=[C:60]([Cl:66])[CH:61]=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=2)[C:56]=1[CH3:73].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:66][C:60]1[CH:61]=[CH:62][C:63]([F:65])=[C:64]2[C:59]=1[N:58]=[C:57]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=1)[C:56]([CH3:73])=[C:55]2[NH:47][C:46]1[C:41]([N:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[N:42][CH:43]=[C:44]([N:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)[CH:45]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631137HCID 59631137, compound

Product 1

HCID 59631093HCID 59631093, 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, 0.052 mmol), 2,5-dimorpholinopyridin-3-amine (0.103 g, 0.39 mmol), 4,8-dichloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.1 g, 0.33 mmol), Pd2dba3 (0.012 g, 0.013 mmol) and sodium tert-butoxide (0.078 g, 0.812 mmol) in toluene (3.3 mL) at 120° C. for 3 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 8-chloro-N-(2,5-dimorpholinopyridin-3-yl)-5-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.67 (1H, m), 8.19 (1H, dt, J=7.8, 1.1 Hz), 7.90-7.92 (1H, td, J=7.7, 1.8 Hz), 7.86 (1H, d, J=12.0 Hz), 7.73 (1H, dd, J=8.4, 5.1 Hz), 7.63 (1H, d, J=2.7 Hz), 7.38 (1H, ddd, J=7.6, 4.8, 1.3 Hz), 7.12 (1H, dd, J=12.9, 8.4 Hz), 6.45 (1H, d, J=2.2 Hz), 3.94 (4H, br. s.), 3.81 (4H, m), 3.18 (4H, br. s.), 3.09 (4H, m), 2.34 (3H, s). Mass Spectrum (ESI) m/e=535.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-fdf1376dad024744b28fa24dc6c26537
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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