Morpholine → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5-fluoro-3-methyl-2-(2-pyridinyl)quinoline

HRID 1618561Notes

Reaction equation

HRID 1618561 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][C:19]=4[F:21])[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[CH2:9][C:8]([CH3:30])([CH3:29])[C:5]2=[N:6][CH:7]=1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]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]>[CH3:30][C:8]1([CH3:29])[C:5]2=[N:6][CH:7]=[C:2]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:3]=[C:4]2[N:10]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[F:21])[N:14]=[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:12]=2[CH3:28])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 672851004-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 509387184-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5-fluoro-3-methyl-2-(2-pyridinyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °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)-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (98.2 mg, 0.21 mmol) (described herein), morpholine (37 mg, 0.42 mmol), Pd2dba3 (29.1 mg, 0.032 mmol), 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (30.3 mg, 0.064 mmol), and sodium tert-butoxide (50.9 mg, 0.53 mmol) in toluene (2.1 mL). The reaction mixture was stirred at 100° C. for 14 h. Purification afforded 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5-fluoro-3-methyl-2-(2-pyridinyl)quinoline as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.75 (1H, dt, J=4.8, 1.5 Hz), 8.03 (1H, dd, J=8.5, 1.3 Hz), 7.85-7.97 (2H, m), 7.58-7.68 (1H, m), 7.50-7.57 (1H, m), 7.36-7.45 (1H, m), 7.10-7.22 (1H, m), 5.70-5.80 (1H, m), 3.86 (1H, dd, J=8.8, 1.6 Hz), 3.66-3.78 (5H, m), 2.92-3.05 (4H, m), 2.40-2.50 (3H, m), 1.54-1.65 (3H, m), 1.45-1.54 (3H, m). Mass Spectrum (ESI) m/e=470 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-204a067fc4ad49ad9620c99b8834ee78
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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