2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631398, compound

HRID 1431735Notes

Reaction equation

HRID 1431735 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]=[N:69][C:70]([N:73]3[CH2:78][CH2:77][C:76]([F:80])([F:79])[CH2:75][CH2:74]3)=[CH:71][CH:72]=2)[C:56]=1[CH3:81].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:80][C:76]1([F:79])[CH2:75][CH2:74][N:73]([C:70]2[N:69]=[CH:68][C:67]([C:57]3[C:56]([CH3:81])=[C:55]([NH:47][C:46]4[C:41]([N:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)=[N:42][CH:43]=[C:44]([N:48]5[CH2:49][CH2:50][O:51][CH2:52][CH2:53]5)[CH:45]=4)[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=3)=[CH:72][CH:71]=2)[CH2:78][CH2:77]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631160HCID 59631160, compound

Product 1

HCID 59631398HCID 59631398, 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 (0.015 g, 0.031 mmol), 2,5-dimorpholinopyridin-3-amine (0.062 g, 0.23 mmol), 4-chloro-2-(6-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)-5,7-difluoro-3-methylquinoline (0.08 g, 0.20 mmol) and Pd2dba3 (0.007 g, 0.008 mmol) and sodium tert-butoxide (0.047 g, 0.49 mmol) in toluene (2.0 mL) at 100° C. for 73 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 2-(6-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (1H, d, J=2.2 Hz), 7.90 (1H, dd, J=8.9, 2.4 Hz), 7.76 (1H, d, J=5.9 Hz), 7.57-7.63 (1H, m), 7.55 (1H, d, J=2.7 Hz), 7.38-7.46 (1H, m), 7.10 (1H, d, J=8.8 Hz), 6.41 (1H, d, J=2.3 Hz), 3.80 (4H, m), 3.60-3.77 (8H, m), 3.13 (2H, br. s.), 2.94-3.04 (4H, m), 2.82 (2H, br. s.), 2.13 (3H, s), 2.03 (4H, m). Mass Spectrum (ESI) m/e=638.2 (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-ec6a5b80dad04ec093d2af739559f0c8
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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