2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 8-chloro-N-(5'-methoxy-5-morpholino-2,3'-bipyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

HRID 1431539Notes

Reaction equation

HRID 1431539 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:43]2[C:48]([NH2:49])=[CH:47][C:46]([N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[CH:45][N:44]=2)[CH:40]=[N:41][CH:42]=1.Cl[C:57]1[C:66]2[C:61](=[C:62]([Cl:67])[CH:63]=[CH:64][CH:65]=2)[N:60]=[C:59]([C:68]2[CH:73]=[C:72]([CH3:74])[CH:71]=[CH:70][N:69]=2)[C:58]=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]>[Cl:67][C:62]1[CH:63]=[CH:64][CH:65]=[C:66]2[C:61]=1[N:60]=[C:59]([C:68]1[CH:73]=[C:72]([CH3:74])[CH:71]=[CH:70][N:69]=1)[C:58]([CH3:75])=[C:57]2[NH:49][C:48]1[C:43]([C:39]2[CH:40]=[N:41][CH:42]=[C:37]([O:36][CH3:35])[CH:38]=2)=[N:44][CH:45]=[C:46]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[CH:47]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596311454,8-Dichloro-3-methyl-2-(4-methylpyridin-2-yl)quinolineHCID 596313095'-Methoxy-5-morpholino-2,3'-bipyridin-3-amine

Product 1

HCID 509080438-chloro-N-(5'-methoxy-5-morpholino-2,3'-bipyridin-3-yl)-3-methyl-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 (0.020 g, 0.042 mmol), 5′-methoxy-5-morpholino-2,3′-bipyridin-3-amine (0.091 g, 0.32 mmol), 4,8-dichloro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.08 g, 0.26 mmol) and Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.063 g, 0.66 mmol) in toluene (2.6 mL) at 100° C. for 48.3 h. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes) to give the desired product 8-chloro-N-(5′-methoxy-5-morpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (1H, d, J=4.9 Hz), 8.35 (1H, s), 8.12 (2H, dd, J=4.6, 2.2 Hz), 7.89 (2H, dd, J=8.0, 2.3 Hz), 7.85 (1H, s), 7.66 (1H, s), 7.53 (1H, t, J=7.6 Hz), 7.34 (1H, m), 7.29 (1H, dd, J=2.7, 1.8 Hz), 5.70-5.72 (1H, m), 3.76 (3H, s), 3.60 (4H, t, J=4.8 Hz), 3.23 (4H, m), 2.46 (3H, s), 2.27 (3H, s). Mass Spectrum (ESI) m/e=553.3 (M+1).

Workup

  1. customwas prepared
  2. customat 100° C.
  3. customfor 48.3 h
  4. customThe crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-af4c6845bb1f42b9b790ad35ced9b0a4
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…