2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631491, compound

HRID 1431460Notes

Reaction equation

HRID 1431460 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](=[C:60]([F:66])[CH:61]=[C:62]([F:65])[CH:63]=2)[N:58]=[C:57]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=2)[C:56]=1[CH3:73].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](=[C:60]([F:66])[CH:61]=[C:62]([F:65])[CH:63]=4)[N:58]=[C:57]([C:67]4[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=4)[C:56]=3[CH3:73])=[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 59631157HCID 59631157, compound

Product 1

HCID 59631491HCID 59631491, 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 (0.026 g, 0.055 mmol), 2,5-dimorpholinopyridin-3-amine (0.109 g, 0.41 mmol), 4-chloro-6,8-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.1 g, 0.34 mmol), Pd2dba3 (0.013 g, 0.014 mmol) and sodium tert-butoxide (0.083 g, 0.86 mmol) in toluene (3.4 mL) at 120° C. for 3 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)-6,8-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3-d) δ ppm 8.73 (1H, dd, J=1.6, 1.2 Hz), 7.89-8.00 (2H, m), 7.62 (1H, d, J=2.5 Hz), 7.40 (1H, ddd, J=7.4, 4.9, 1.4 Hz), 7.21-7.26 (2H, m), 6.70 (1H, br. s.), 6.19 (1H, m), 3.95-3.93 (4H, br. s.), 3.77-3.75 (4H, br. s.), 3.25 (4H, br s), 2.9-2.95 (4H, m), 2.44 (3H, s). Mass Spectrum (ESI) m/e=519.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-84a04a6879f54e68b11003f93719979e
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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