Toluene → HCID 59631369, compound

HRID 1431327Notes

Reaction equation

HRID 1431327 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][CH:61]=[C:62]([Cl:66])[C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=2)[C:56]=1[CH3:73].C1(C)C=CC=CC=1.CC(C)([O-])C.[Na+]>O.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]>[Cl:66][C:62]1[C:63]([F:65])=[C:64]2[C:59](=[CH:60][CH:61]=1)[N:58]=[C:57]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=1)[C:56]([CH3:73])=[C:55]2[NH:47][C:46]1[C:41]([N:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[N:42][CH:43]=[C:44]([N:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)[CH:45]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631414HCID 59631414, compound

Product 1

HCID 59631369HCID 59631369, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.018 g, 0.038 mmol), 2,5-dimorpholinopyridin-3-amine (0.074 g, 0.281 mmol), 4,6-dichloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.072 g, 0.234 mmol) and Pd2dba3 (8.59 mg, 9.38 μmol) in toluene (2.3 mL, 0.23 mmol) was added sodium t-butoxide (0.056 g, 0.59 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. The reaction was cooled to rt and diluted with water (25 mL). The mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL). The organic layers were combined and dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (0 to 100% EtOAc/DCM) to give the desired product 6-chloro-N-(2,5-di-4-morpholinyl-3-pyridinyl)-5-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.70 (1H, dd, J=4.7, 1.2 Hz), 7.90 (3H, m), 7.57-7.73 (3H, m), 7.39 (1H, m), 6.41 (1H, s), 3.94 (4H, br. s.), 3.80 (4H, br m), 3.22 (4H, br. s.), 3.06 (4H, br m), 2.26 (3H, s). Mass Spectrum (ESI) m/e=535.3 (M+1).

Workup

  1. temperatureThe reaction was cooled to rt
  2. extractionThe mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography on silica gel (0 to 100% EtOAc/DCM)

Sources & evidence

ORD record
ord-2cd94106295f40daadb3b75e89aae91d
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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