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-methyl-3-pyridinyl)quinoline

HRID 1618528Notes

Reaction equation

HRID 1618528 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[C:23]([CH3:28])=[N:24][CH:25]=[CH:26][CH:27]=4)[C:12]=3[CH3:29])[CH2:9][C:8]([CH3:31])([CH3:30])[C:5]2=[N:6][CH:7]=1.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[CH3:31][C:8]1([CH3:30])[C:5]2=[N:6][CH:7]=[C:2]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]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[C:23]([CH3:28])=[N:24][CH:25]=[CH:26][CH:27]=3)[C:12]=2[CH3:29])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672848974-(6-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-methylpyridin-3-yl)quinoline

Product 1

HCID 509389524-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-methyl-3-pyridinyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °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-methylpyridin-3-yl)-quinoline (41 mg, 0.086 mmol), Pd2dba3 (7.86 mg, 8.59 μmol), morpholine (8.23 μL, 0.094 mmol), sodium tert-butoxide (16.5 mg, 0.172 mmol) and XPhos (8.19 mg, 0.017 mmol) in toluene (1.5 mL) and heating in the microwave for 1 h at 120° C. After purification 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-methyl-3-pyridinyl)quino line was obtained as a yellow film. 1H NMR (400 MHz, chloroform-d) δ ppm 8.66 (1H, dt, J=4.9, 1.7 Hz), 7.78-7.88 (2H, m), 7.67 (1H, d, J=7.6 Hz), 7.57-7.63 (1H, m), 7.30-7.40 (2H, m), 5.84 (1H, d, J=2.0 Hz), 3.70-3.92 (6H, m), 2.93-3.12 (4H, m), 2.42 (3H, s), 2.08 (3H, s), 1.66 (3H, m), 1.59 (3H, s). Mass Spectrum (ESI) m/e=484 (M+1).

Workup

  1. customPrepared
  2. customAfter purification 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-methyl-3-pyridinyl)quino line
  3. customwas obtained as a yellow film

Sources & evidence

ORD record
ord-7e2484e914984cfe96bfb90a472021fc
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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