2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631554, compound

HRID 1431496Notes

Reaction equation

HRID 1431496 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:72]=[CH:71][C:70]([CH3:73])=[CH:69][C:68]=2[CH3:74])[C:56]=1[CH3:75].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]>[CH3:74][C:68]1[CH:69]=[C:70]([CH3:73])[CH:71]=[CH:72][C:67]=1[C:57]1[C:56]([CH3:75])=[C:55]([NH:47][C:46]2[C:41]([N:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)=[N:42][CH:43]=[C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)[CH:45]=2)[C:64]2[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631063HCID 59631063, compound

Product 1

HCID 59631554HCID 59631554, 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 (0.022 g, 0.045 mmol), 2,5-dimorpholinopyridin-3-amine (0.090 g, 0.34 mmol), 4-chloro-2-(2,4-dimethylphenyl)-5,7-difluoro-3-methylquinoline (0.090 g, 0.28 mmol), Pd2dba3 (10.4 mg, 0.011 mmol) and sodium tert-butoxide (0.068 g, 0.71 mmol) in toluene (2.8 mL) at 120° C. for 3.3 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 2-(2,4-dimethylphenyl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.46 (1H, s), 8.70 (1H, d, J=4.8 Hz), 8.02 (1H, td, J=7.8, 1.8 Hz), 7.98 (1H, d, J=5.7 Hz), 7.89 (1H, dt, J=7.8, 1.2 Hz), 7.67 (1H, br. dd, J=2.2, 1.8 Hz), 7.65 (2H, dt, J=8.4, 1.6 Hz), 7.52 (1H, ddd, J=7.6, 4.9, 1.4 Hz), 7.47 (1H, ddd, J=12.1, 9.2, 2.5 Hz), 6.10 (1H, br. s), 3.48 (4H, br s), 3.40-3.30 (8H, m), 2.27 (3H, s). Mass Spectrum (ESI) m/e=546.3 (M+1).

Workup

  1. customwas prepared
  2. customat 120° C.
  3. customfor 3.3 h
  4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)

Sources & evidence

ORD record
ord-0cf94f0bdbd0413ebb47a9c3cbfc8206
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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