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

HRID 1431483Notes

Reaction equation

HRID 1431483 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[CH:73]([CH3:75])[CH3:74].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[CH:73]([CH3:75])[CH3:74])=[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 596313654-Chloro-7-fluoro-3-isopropyl-2-(4-methylpyridin-2-yl)quinoline

Product 1

HCID 59631333N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-isopropyl-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 (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.106 g, 0.40 mmol), 4-chloro-7-fluoro-3-isopropyl-2-(4-methylpyridin-2-yl)quinoline (0.105 g, 0.33 mmol), Pd2dba3 (0.012 g, 0.013 mmol) and sodium tert-butoxide (0.080 g, 0.83 mmol) in toluene (3.3 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-isopropyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.58 (1H, dd, J=5.1, 0.6 Hz), 7.96 (1H, br s), 7.55-7.62 (2H, m), 7.52 (1H, m), 7.22 (1H, m), 7.13 (1H, br s), 7.07 (2H, dd, J=4.6, 1.1 Hz), 6.19 (1H, s), 3.96-3.91 (4H, m), 3.71 (4H, m), 3.50 (2H, br. s.), 3.40 (1H, m), 3.00 (1H, br s), 2.86 (4H, t, J=4.8 Hz), 2.48 (3H, s), 1.52 (3H, d, J=7.4 Hz), 1.13 (3H, d, J=7.4 Hz). Mass Spectrum (ESI) m/e=543.2 (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-1b6617bfc50e45dfa608f73a6f98d8a7
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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