2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 67284623, compound

HRID 1618687Notes

Reaction equation

HRID 1618687 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]([C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=2)[C:3]=1[CH3:21].[CH3:22][C:23]1([CH3:38])[C:27]2=[N:28][CH:29]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:31]=[C:26]2[NH:25][CH2:24]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>[CH3:22][C:23]1([CH3:38])[C:27]2=[N:28][CH:29]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:31]=[C:26]2[N:25]([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]([C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=3)[C:3]=2[CH3:21])[CH2:24]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596311504-Chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

Product 1

HCID 67284623HCID 67284623, compound

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-(4-methylpyridin-2-yl)quinoline (65 mg, 0.213 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (54.7 mg, 0.235 mmol), Pd2dba3 (29.3 mg, 0.032 mmol), XPhos (30.5 mg, 0.064 mmol), sodium tert-butoxide (51 mg, 0.533 mmol), and toluene (2.1 mL) at 100° C. for 2 h. 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-(4-methyl-2-pyridinyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 8.59 (1H, s), 7.75 (1H, d), 7.71 (2H, m), 7.55 (1H, br. s.), 7.00 (1H, m), 5.76 (1H, s), 3.67-3.92 (6H, m), 3.00 (4H, br. s.), 2.46 (3H, s), 2.41 (3H, s), 1.57 (3H, br. s.), 1.51 (3H, br. s.). Mass Spectrum (ESI) m/e=502.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-d71cc73fde414d6b9f65083d9c24d8c5
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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