2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631442, compound

HRID 1431731Notes

Reaction equation

HRID 1431731 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](=[CH:54][C:55]([F:60])=[CH:56][C:57]=2[F:59])[N:52]=[C:51]([C:61]2[CH:62]=[N:63][C:64]([N:67]3[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]3)=[CH:65][CH:66]=2)[C:50]=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]>[F:59][C:57]1[CH:56]=[C:55]([F:60])[CH:54]=[C:53]2[C:58]=1[C:49]([NH:47][C:43]1[CH:44]=[N:45][CH:46]=[C:41]([N:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)[CH:42]=1)=[C:50]([CH3:73])[C:51]([C:61]1[CH:62]=[N:63][C:64]([N:67]3[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]3)=[CH:65][CH:66]=1)=[N:52]2

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 59631316HCID 59631316, compound

Product 1

HCID 59631442HCID 59631442, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure S using of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.020 g, 0.043 mmol), 5-morpholinopyridin-3-amine (0.057 g, 0.320 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(6-(piperazin-1-yl)pyridin-3-yl)quinoline (0.1 g, 0.27 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.049 g, 0.51 mmol) in toluene (2.7 mL) at 100° C. for 2.5 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(6-(piperazin-1-yl)pyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.45 (2H, dd, J=4.9, 2.2 Hz), 7.89 (1H, dd, J=8.9, 2.4 Hz), 7.79 (1H, d, J=2.5 Hz), 7.56-7.60 (2H, m), 7.35-7.41 (1H, m), 6.93 (1H, d, J=8.8 Hz), 6.55 (1H, t, J=2.3 Hz), 3.70 (4H, m), 3.55 (4H, m), 3.08 (4H, m), 2.85 (4H, m), 2.19 (3H, s). Mass Spectrum (ESI) m/e=518.2 (M+1).

Workup

  1. customwas prepared
  2. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-ed514611c08c485d95a549e63205f0ba
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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