2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631533, compound

HRID 1431504Notes

Reaction equation

HRID 1431504 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]=[C:71]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[CH:70]=[CH:69][N:68]=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]=[C:71]([C:73]5[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=5)[CH:70]=[CH:69][N: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 59631051HCID 59631051, compound

Product 1

HCID 59631533HCID 59631533, 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 (0.021 g, 0.044 mmol), 2,5-dimorpholinopyridin-3-amine (0.086 g, 0.33 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-phenylpyridin-2-yl)quinoline (0.1 g, 0.27 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.066 g, 0.68 mmol) in toluene (2.7 mL) at 120° C. for 3.25 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-(4-phenylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.75 (1H, d, J=5.1 Hz), 8.10 (1H, s), 7.76 (3H, m), 7.64-7.61 (3H, m), 7.57-7.49 (3H, m), 7.03 (1H, ddd, J=13.5, 8.4, 2.5 Hz), 6.48 (1H, br. s.), 3.93 (4H, app t, J=4.8 Hz), 3.81 (4H, app t, J=4.5 Hz), 3.25 (4H, br. s), 3.09 (11H, app t, J=4.9 Hz), 2.25 (3H, s). Mass Spectrum (ESI) m/e=595.3 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 3.25 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-f14ba29d6d844a5fad32bf2e161644f9
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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