2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631303, compound

HRID 1431741Notes

Reaction equation

HRID 1431741 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](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:72]=[CH:71][N:70]=[C:69]([N:73]3[CH2:77][CH2:76][CH2:75][CH2:74]3)[CH:68]=2)[C:56]=1[CH3:78].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]>[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:72]=[CH:71][N:70]=[C:69]([N:73]5[CH2:74][CH2:75][CH2:76][CH2:77]5)[CH:68]=4)[C:56]=3[CH3:78])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631468HCID 59631468, compound

Product 1

HCID 59631303HCID 59631303, 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 (0.021 g, 0.044 mmol), 2,5-dimorpholinopyridin-3-amine (0.088 g, 0.33 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(2-(pyrrolidin-1-yl)pyridin-4-yl)quinoline (0.1 g, 0.28 mmol) and Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.067 g, 0.70 mmol) in toluene (2.8 mL) at 100° C. for 1.0 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 N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(2-(pyrrolidin-1-yl)pyridin-4-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.42 (1H, dd, J=2.3, 0.6 Hz), 7.84 (1H, dd, J=8.8, 2.5 Hz), 7.73 (1H, d, J=5.5 Hz), 7.59 (1H, dd, J=9.9, 1.7 Hz), 7.55 (1H, d, J=2.7 Hz), 7.35-7.43 (1H, m), 6.58 (1H, d, J=8.6 Hz), 6.39 (1H, d, J=2.5 Hz), 3.59-3.81 (8H, m), 3.47 (4H, t, J=6.5 Hz), 3.15 (2H, br. s.), 2.94-3.05 (4H, m), 2.83 (2H, br. s.), 2.13 (3H, s), 1.93-2.04 (4H, m). Mass Spectrum (ESI) m/e=588.2 (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-9af9172d00fa43af83ea8f789f1183cb
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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