2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 8-chloro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431534Notes

Reaction equation

HRID 1431534 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[CH:42]=[C:43]([NH2:47])[CH:44]=[N:45][CH:46]=2)[CH2:37][CH2:36]1.Cl[C:49]1[C:58]2[C:53](=[C:54]([Cl:59])[CH:55]=[CH:56][CH:57]=2)[N:52]=[C:51]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][N:61]=2)[C:50]=1[CH3:66].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:59][C:54]1[CH:55]=[CH:56][CH:57]=[C:58]2[C:53]=1[N:52]=[C:51]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][N:61]=1)[C:50]([CH3:66])=[C:49]2[NH:47][C:43]1[CH:44]=[N:45][CH:46]=[C:41]([N:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)[CH:42]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 596310354,8-Dichloro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 509080468-chloro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine

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 (0.026 g, 0.055 mmol), 5-morpholinopyridin-3-amine (0.074 g, 0.42 mmol), 4,8-dichloro-3-methyl-2-(pyridin-2-yl)quinoline (0.1 g, 0.35 mmol) and Pd2dba3 (0.013 g, 0.014 mmol) and sodium tert-butoxide (0.083 g, 0.87 mmol) in toluene (3.5 mL) at 100° C. for 1.1 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1)) to give the desired product 8-chloro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69-8.73 (2H, m), 7.95-8.06 (3H, m), 7.92 (1H, dd, J=7.4, 1.2 Hz), 7.81 (1H, d, J=2.3 Hz), 7.50-7.56 (3H, m), 6.56 (1H, t, J=2.4 Hz), 3.70 (4H, m), 3.06 (4H, m), 2.25 (3H, s). Mass Spectrum (ESI) m/e=432.1 (M+1).

Workup

  1. customwas prepared
  2. customat 100° C.
  3. customfor 1.1 h
  4. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1))

Sources & evidence

ORD record
ord-8e5183cad26a4f24bad65da6372c7129
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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