2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 67507807, compound

HRID 1431528Notes

Reaction equation

HRID 1431528 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:66]=[CH:65][N:64]=[C:63]([O:67][CH3:68])[CH:62]=2)[C:50]=1[CH3:69].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]([CH3:69])[C:51]([C:61]1[CH:66]=[CH:65][N:64]=[C:63]([O:67][CH3:68])[CH:62]=1)=[N:52]2

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 59631439HCID 59631439, compound

Product 1

HCID 67507807HCID 67507807, 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 (0.024 g, 0.050 mmol), 5-morpholinopyridin-3-amine (0.067 g, 0.37 mmol), 4-chloro-5,7-difluoro-2-(2-methoxypyridin-4-yl)-3-methylquinoline (0.1 g, 0.31 mmol), Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.075 g, 0.78 mmol) in toluene (3.1 mL) at 100° C. for 46.5 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 5,7-difluoro-2-(2-methoxypyridin-4-yl)-3-methyl-N-(5-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (1H, d, J=1.6 Hz), 8.30-8.34 (1H, dd, J=5.1, 0.6 Hz), 7.80 (1H, d, J=2.3 Hz), 7.64 (1H, m), 7.58 (1H, d, J=2.3 Hz), 7.43-7.51 (1H, m), 7.21 (1H, dd, J=5.2, 1.5 Hz), 7.03 (1H, s), 6.59 (1H, t, J=2.3 Hz), 3.92 (3H, s), 3.70 (4H, m), 3.08 (4H, m), 2.08 (3H, s). Mass Spectrum (ESI) m/e=464.1 (M+1).

Workup

  1. customwas prepared
  2. customat 100° C.
  3. customfor 46.5 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-006bb058907c45d49d9620aceea9b299
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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