2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine

HRID 1431485Notes

Reaction equation

HRID 1431485 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:65])=[CH:62][CH:63]=2)[N:58]=[C:57]([C:66]2[CH:71]=[C:70]([CH3:72])[CH:69]=[CH:68][N:67]=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](=[CH:60][C:61]([F:65])=[CH:62][CH:63]=4)[N:58]=[C:57]([C:66]4[CH:71]=[C:70]([CH3:72])[CH:69]=[CH:68][N:67]=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 596310864-Chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline

Product 1

HCID 59631352N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine

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, 0.31 mmol), 4-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.075 g, 0.26 mmol), Pd2dba3 (9.58 mg, 10.46 μmol) and sodium tert-butoxide (0.063 g, 0.65 mmol) in toluene (2.6 mL) at 120° C. for 4.6 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)-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.58 (2H, d, J=5.1 Hz), 7.81 (2H, m), 7.69 (1H, s), 7.59 (1H, m), 7.32-7.25 (1H, m), 7.22 (1H, d, J=4.9 Hz), 6.74 (1H, s), 6.21 (1H, m), 3.92 (4H, t, J=4.7 Hz), 3.74 (4H, app t, J=5.0, 4.7 Hz), 3.23 (4H, br. s.), 2.92 (6H, app t, J=4.7 Hz), 2.49 (3H, s), 2.36 (3H, s). Mass Spectrum (ESI) m/e=515.2 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 4.6 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-bf85d41baa1a4d45bbec62f3020d90da
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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