2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631409, compound

HRID 1431718Notes

Reaction equation

HRID 1431718 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:68]=[CH:69][C:70]([N:73]3[CH2:78][CH2:77][O:76][CH2:75][CH2:74]3)=[N:71][CH:72]=2)[C:56]=1[CH3:79].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]=[N:71][C:70]([N:73]5[CH2:74][CH2:75][O:76][CH2:77][CH2:78]5)=[CH:69][CH:68]=4)[C:56]=3[CH3:79])=[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 59631102HCID 59631102, compound

Product 1

HCID 59631409HCID 59631409, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure S using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.020 g, 0.043 mmol), 2,5-dimorpholinopyridin-3-amine (0.084 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 (0.079 g, 0.82 mmol) in toluene (2.7 mL) at 120° C. for 1.9 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(6-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (1H, dd, J=2.4, 0.7 Hz), 7.90 (1H, dd, J=8.8, 2.5 Hz), 7.75 (1H, d, J=5.9 Hz), 7.60 (1H, ddd, J=10.0, 2.5, 1.0 Hz), 7.55 (1H, d, J=2.5 Hz), 7.42 (1H, dd, J=4.0, 2.6 Hz), 6.98 (1H, d, J=8.6 Hz), 6.41 (1H, d, J=2.5 Hz), 3.69-3.78 (6H, m), 3.61-3.69 (6H, m), 3.52-3.61 (4H, m), 3.14 (2H, br. s.), 2.95-3.05 (4H, m), 2.83 (2H, br. s.), 2.12 (3H, s). Mass Spectrum (ESI) m/e=604.3 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 1.9 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-eedfcae60c9f4bc0963adde911f3d762
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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