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

HRID 1431508Notes

Reaction equation

HRID 1431508 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[CH:42]=[C:43]([NH2:47])[CH:44]=[N:45][CH:46]=2)[CH2:37][CH2:36]1.Cl[C:49]1[C:58]2[C:53](=[CH:54][C:55]([F:60])=[CH:56][C:57]=2[F:59])[N:52]=[C:51]([C:61]2[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][N:62]=2)[C:50]=1[CH3:68].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[F:59][C:57]1[CH:56]=[C:55]([F:60])[CH:54]=[C:53]2[C:58]=1[C:49]([NH:47][C:43]1[CH:44]=[N:45][CH:46]=[C:41]([N:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)[CH:42]=1)=[C:50]([CH3:68])[C:51]([C:61]1[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][N:62]=1)=[N:52]2

Participants

6

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 596312074-Chloro-5,7-difluoro-3-methyl-2-(5-methylpyridin-2-yl)quinoline

Product 1

HCID 596314895,7-difluoro-3-methyl-2-(5-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.023 g, 0.047 mmol), 5-morpholinopyridin-3-amine (0.064 g, 0.35 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(5-methylpyridin-2-yl)quinoline (0.09 g, 0.30 mmol) Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.071 g, 0.74 mmol) in toluene (2.7 mL) at 120° C. for 10 days. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 5,7-difluoro-3-methyl-2-(5-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.55 (1H, d, J=4.9 Hz), 7.95 (1H, d, J=2.5 Hz), 7.81 (1H, d, J=2.3 Hz), 7.63 (2H, m), 7.19 (1H, m), 6.98-7.07 (2H, m), 6.62 (1H, app t, J=2.4 Hz), 3.86 (4H, app t, J=4.9 Hz), 3.19 (9H, app t, J=4.9 Hz), 2.48 (3H, s), 2.15 (3H, s). Mass Spectrum (ESI) m/e=448.1 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 10 days
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-4fb2514658cb44068a13571e0fbc4976
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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