Morpholine → 2-(2,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methylquinoline

HRID 1618564Notes

Reaction equation

HRID 1618564 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[C:18]([CH3:19])=[C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26](I)[CH:27]=3)[C:22]([CH3:31])([CH3:30])[CH2:21]2)[C:16]2[C:11](=[CH:12][C:13]([F:32])=[CH:14][CH:15]=2)[N:10]=1.[NH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC([O-])(C)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]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[C:18]([CH3:19])=[C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH:27]=3)[C:22]([CH3:31])([CH3:30])[CH2:21]2)[C:16]2[C:11](=[CH:12][C:13]([F:32])=[CH:14][CH:15]=2)[N:10]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672848032-(2,5-Difluorophenyl)-7-fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methylquinoline

Product 1

HCID 509387172-(2,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methylquinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Prepared according to procedure N using 2-(2,5-difluorophenyl)-7-fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methylquinoline (166 mg, 0.31 mmol) (described herein), morpholine (53.1 μL, 0.61 mmol), Pd2dba3 (41.9 mg, 0.046 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (43.6 mg, 0.091 mmol), and sodium 2-methylpropan-2-olate (88 mg, 0.915 mmol) in toluene (3.0 mL). The reaction mixture was stirred at 105° C. for 1 h. Purification afforded 2-(2,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methylquinoline as a yellow oil. 1H NMR (500 MHz, chloroform-d) δ ppm 7.88-7.99 (1H, m), 7.76-7.84 (1H, m), 7.27-7.35 (2H, m), 7.16 (2H, m), 7.09 (1H, d, J=8.1 Hz), 6.30-6.38 (1H, d), 5.57-5.69 (1H, s), 3.75 (6H, m), 2.98 (4H, d, J=2.4 Hz), 2.18 (3H, s), 1.52 (3H, s), 1.46 (3H, s). Mass Spectrum (ESI) m/e=504 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-54b27cfefc814b0782bc0245ebe92eab
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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