Morpholine → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline

HRID 1618550Notes

Reaction equation

HRID 1618550 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[S:28]([CH3:31])(=[O:30])=[O:29])[C:12]=3[CH3:32])[CH2:9][C:8]([CH3:34])([CH3:33])[C:5]2=[N:6][CH:7]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C1(P(C2CCCCC2)C2(CCC)CC(CCC)=CC(CCC)=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:8]1([CH3:33])[C:5]2=[N:6][CH:7]=[C:2]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:3]=[C:4]2[N:10]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[S:28]([CH3:31])(=[O:29])=[O:30])[C:12]=2[CH3:32])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 67284726HCID 67284726, compoundHCID 866642752-(Dicyclohexylphosphino)-2,4,6-tri-1-propyl-1,1-biphenyl

Product 1

HCID 509388264-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Prepared according to procedure N using 4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-quinoline (42 mg, 0.078 mmol) (described herein), morpholine (14 μL, 0.16 mmol), Pd2dba3 (5.0 mg, 5.4 μmol), 2-(dicyclohexylphosphino)-2,4,6-tri-1-propyl-1,1-biphenyl (5.6 mg, 0.012 mmol), and sodium tert-butoxide (15 mg, 0.155 mmol) in toluene (1.3 mL), and heating at 105° C. for 18 h. Purification afforded 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline as a yellow powder. Compound is rotameric. 1H NMR (400 MHz, chloroform-d) δ ppm 8.15-8.29 (1H, m), 7.84-8.09 (1H, m), 7.77-7.83 (1H, m), 7.69-7.77 (2H, m), 7.55-7.69 (1H, m), 7.43-7.54 (1H, m), 7.31-7.43 (1H, m), 5.86 and 6.10 (1H, m), 4.05 (1H, m), 3.67-3.87 (5H, m), 3.14 (1H, m), 2.90-3.12 (6H, m), 2.00-2.16 (1H, m), 1.92 (2H, s), 1.46-1.68 (6H, m). Mass Spectrum (ESI) m/e=547 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-29c07ddc5be7431bb67ecf22ac9f9b06
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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