2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631565, compound

HRID 1431481Notes

Reaction equation

HRID 1431481 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:75]=[CH:74][CH:73]=[C:72]3[C:68]=2[CH:69]=[N:70][N:71]3[CH3:76])[C:56]=1[CH3:77].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:75]=[CH:74][CH:73]=[C:72]5[C:68]=4[CH:69]=[N:70][N:71]5[CH3:76])[C:56]=3[CH3:77])=[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 59631032HCID 59631032, compoundHCID 596310462,5-Dimorpholinopyridin-3-amine

Product 1

HCID 59631565HCID 59631565, 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 (0.020 g, 0.042 mmol), 2,5-dimorpholinopyridin-3-amine (0.083 g, 0.32 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(1-methyl-1H-indazol-4-yl)quinoline (0.090 g, 0.26 mmol), Pd2dba3 (9.6 mg, 10.50 μmol) and sodium tert-butoxide (0.063 g, 0.66 mmol) in toluene (2.6 mL) at 120° C. for 3.3 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)-5,7-difluoro-3-methyl-2-(1-methyl-1H-indazol-4-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.84 (1H, s), 7.80 (1H, br m), 7.65 (1H, d, J=2.5 Hz), 7.63 (1H, br. s.), 7.53 (4H, s), 7.54 (2H, m), 7.25 (1H, m), 7.05 (1H, ddd, J=13.4, 8.5, 2.7 Hz), 6.41 (1H, br. s.), 4.16 (3H, s), 3.92 (4H, app t, J=4.8 Hz), 3.85 (4H, app dd, J=5.7, 3.9 Hz), 3.25 (4H, br s.), 3.08 (11H, app dd, J=4.3, 2.3 Hz), 2.06 (3H, s). Mass Spectrum (ESI) m/e=572.2 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 3.3 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-d157eb47da3b4c108e46a3991d0584a7
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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