2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 67508005, compound

HRID 1431518Notes

Reaction equation

HRID 1431518 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]([O:73][CH2:74][CH3:75])=[CH:71][CH:72]=2)[C:56]=1[CH3:76].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:68]=[N:69][C:70]([O:73][CH2:74][CH3:75])=[CH:71][CH:72]=4)[C:56]=3[CH3:76])=[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 67508049HCID 67508049, compound

Product 1

HCID 67508005HCID 67508005, 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 (0.023 g, 0.048 mmol), 2,5-dimorpholinopyridin-3-amine (0.095 g, 0.36 mmol), 4-chloro-2-(6-ethoxypyridin-3-yl)-5,7-difluoro-3-methylquinoline (0.1 g, 0.30 mmol), Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.045 g, 0.47 mmol) in toluene (3.0 mL) at 100° C. for 2 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)-2-(6-ethoxypyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.46 (1H, d, J=2.0 Hz), 8.01 (1H, dd, J=8.6, 2.4 Hz), 7.79 (1H, d, J=5.6 Hz), 7.65 (1H, dd, J=9.8, 1.7 Hz), 7.56 (1H, d, J=2.4 Hz), 7.47 (1H, ddd, J=13.1, 9.4, 2.4 Hz), 6.96 (1H, d, J=8.6 Hz), 6.44 (1H, d, J=2.7 Hz), 4.40 (2H, q, J=6.9 Hz), 3.58-3.83 (9H, m), 3.16 (2H, br. s.), 2.94-3.06 (5H, m), 2.84 (2H, br. s.), 2.11 (3H, s), 1.37 (3H, t, J=7.1 Hz). Mass Spectrum (ESI) m/e=563.3 (M+1).

Workup

  1. customwas prepared
  2. customat 100° C.
  3. customfor 2 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-df15e1b1c71a49868f8a735f41eaea5f
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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