2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631509, compound

HRID 1431726Notes

Reaction equation

HRID 1431726 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]=[CH:63][C:64]([N:67]3[CH2:72][CH2:71][O:70][CH2:69][CH2:68]3)=[N: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:66]=[N:65][C:64]([N:67]3[CH2:72][CH2:71][O:70][CH2:69][CH2:68]3)=[CH:63][CH:62]=1)=[N:52]2

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 59631102HCID 59631102, compound

Product 1

HCID 59631509HCID 59631509, 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, 0.32 mmol), 4-(5-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)pyridin-2-yl)morpholine (0.1 g, 0.27 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.064 g, 0.67 mmol) in toluene (2.7 mL) at 100° C. for 2.5 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1)) to give the desired product 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(6-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (1H, dd, J=2.5, 0.6 Hz), 8.45 (1H, d, J=1.6 Hz), 7.92 (1H, dd, J=8.9, 2.4 Hz), 7.79 (1H, d, J=2.5 Hz), 7.57-7.62 (2H, m), 7.35-7.42 (1H, m), 6.96 (1H, d, J=8.6 Hz), 6.56 (1H, t, J=2.3 Hz), 3.71 (8H, dt, J=12.1, 4.8 Hz), 3.53-3.59 (4H, m), 3.05-3.11 (4H, m), 2.18 (3H, s). Mass Spectrum (ESI) m/e=519.2 (M+1).

Workup

  1. customwas prepared
  2. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1))

Sources & evidence

ORD record
ord-a710e63f275b48b9aae0bda35a9bed4d
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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