2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(3-(trifluoromethyl)benzyl)quinoline

HRID 1618685Notes

Reaction equation

HRID 1618685 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:3]=1[CH3:25].[CH3:26][C:27]1([CH3:42])[C:31]2=[N:32][CH:33]=[C:34]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH:35]=[C:30]2[NH:29][CH2:28]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[CH3:26][C:27]1([CH3:42])[C:31]2=[N:32][CH:33]=[C:34]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH:35]=[C:30]2[N:29]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=3[F:12])[N:5]=[C:4]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[C:3]=2[CH3:25])[CH2:28]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 866642794-Chloro-5,7-difluoro-3-methyl-2-(3-(trifluoromethyl)benzyl)quinoline

Product 1

HCID 509394714-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(3-(trifluoromethyl)benzyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-5,7-difluoro-3-methyl-2-(3-(trifluoromethyl)benzyl)quinoline (50 mg, 0.135 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (31.4 mg, 0.135 mmol), Pd2dba3 (12 mg, 0.013 mmol), XPhos (13 mg, 0.027 mmol), sodium tert-butoxide (39 mg, 0.404 mmol), and toluene (1.3 mL) at 100° C. for 30 min. Purification by reverse-phase HPLC (0-90% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(3-(trifluoromethyl)benzyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 7.60-7.66 (1H, m), 7.40-7.55 (5H, m), 6.94-7.01 (1H, m), 5.53-5.56 (1H, m), 4.47 (2H, s), 3.78-3.85 (1H, m), 3.67-3.78 (4H, m), 3.57 (1H, d, J=8.8 Hz), 2.86-2.97 (4H, m), 2.22 (3H, s), 1.48-1.58 (3H, m), 1.46 (3H, s). Mass Spectrum (ESI) m/e=569.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC (0-90% acetonitrile in water)

Sources & evidence

ORD record
ord-81cb4911d22e4de7b97ff0fc94c39a7f
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…