Morpholine → 4-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline

HRID 1618545Notes

Reaction equation

HRID 1618545 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[C:29](I)[CH:30]=4)[C:25]([CH3:34])([CH3:33])[CH2:24]3)=[C:7]([CH3:22])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])=[N:9]2)=[CH:4][CH:3]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.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]>[CH3:34][C:25]1([CH3:33])[C:26]2[C:31](=[CH:30][C:29]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:28][CH:27]=2)[N:23]([C:6]2[C:5]3[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])[C:7]=2[CH3:22])[CH2:24]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 672849377-Fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methyl-2-(2-(methylsulfonyl)phenyl)quinolineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 509394764-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Prepared according to procedure N using 7-fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (68 mg, 0.12 mmol) (described herein), morpholine (20 μL, 0.23 mmol), Pd2dba3 (7.4 mg, 8.1 μmol), 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (8.2 mg, 0.017 mmol), and sodium tert-butoxide (22.1 mg, 0.23 mmol) in toluene (2.2 mL), and heated at 95° C. for 15 h. After purification 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline was obtained as a yellow glass. 1H NMR (400 MHz, chloroform-d) δ ppm 8.17-8.28 (1H, m), 7.94 and 8.08 (1H, m), 7.74-7.84 (1H, m), 7.63-7.74 (2H, m), 7.42-7.53 (1H, m), 7.29-7.40 (1H, m), 6.98-7.13 (1H, m), 6.21-6.39 (1H, m), 5.65 and 5.82 (1H, m), 3.94 and 3.66 (1H, m), 3.69-3.82 (5H, m), 3.15 (1H, m), 3.05-3.12 (3H, m), 2.84-3.05 (4H, m), 1.94 (2H, s), 1.47-1.55 (3H, m), 1.40-1.47 (3H, m). Mass Spectrum (ESI) m/e=546 (M+1).

Workup

  1. customPrepared
  2. customAfter purification 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline
  3. customwas obtained as a yellow glass

Sources & evidence

ORD record
ord-569823a75a444c31832429a0beb92804
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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