2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631460, compound

HRID 1431744Notes

Reaction equation

HRID 1431744 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:68]=[N:69][C:70]([N:73]3[CH2:77][CH2:76][CH2:75][CH2:74]3)=[CH:71][CH:72]=2)[C:56]=1[CH3:78].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:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:68]=[N:69][C:70]([N:73]5[CH2:74][CH2:75][CH2:76][CH2:77]5)=[CH:71][CH:72]=4)[C:56]=3[CH3:78])=[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 59631456Quinoline, 4-chloro-5,7-difluoro-3-methyl-2-[6-(1-pyrrolidinyl)-3-pyridinyl]-

Product 1

HCID 59631460HCID 59631460, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure S using of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.018 g, 0.037 mmol), 2,5-dimorpholinopyridin-3-amine (0.074 g, 0.28 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(6-(pyrrolidin-1-yl)pyridin-3-yl)quinoline (0.084 g, 0.23 mmol) and Pd2dba3 (0.009 g, 0.009 mmol) and sodium tert-butoxide (0.056 g, 0.58 mmol) in toluene (2.3 mL) at 100° C. for 2.5 h. The crude product was purified by column chromatography on alumina (0-60% EtOAc/hexanes) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(6-(pyrrolidin-1-yl)-pyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.42 (1H, dd, J=2.4, 0.5 Hz), 7.84 (1H, dd, J=8.7, 2.4 Hz), 7.73 (1H, d, J=5.7 Hz), 7.56-7.62 (1H, m), 7.55 (1H, d, J=2.5 Hz), 7.39 (1H, ddd, J=13.2, 9.4, 2.4 Hz), 6.58 (1H, d, J=8.6 Hz), 6.39 (1H, d, J=2.7 Hz), 3.61-3.82 (8H, m), 3.47 (4H, t, J=6.6 Hz), 3.15 (2H, br. s.), 2.94-3.05 (4H, m), 2.84 (2H, br. s.), 2.13 (3H, s), 1.95-2.03 (4H, m). Mass Spectrum (ESI) m/e=588.2 (M+1).

Workup

  1. customwas prepared
  2. customThe crude product was purified by column chromatography on alumina (0-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2d8f2eba6a6745bfb559bbd90710ae08
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…