Morpholine → 4-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-(1-methylethyl)-2-(2-pyridinyl)quinoline

HRID 1618519Notes

Reaction equation

HRID 1618519 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][N:23]=4)[C:12]=3[CH:28]([CH3:30])[CH3:29])[CH2:9][C:8]([CH3:32])([CH3:31])[C:5]2=[N:6][CH:7]=1.CC(C)([O-])C.[Na+].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.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]>[CH3:32][C:8]1([CH3:31])[C:5]2=[N:6][CH:7]=[C:2]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]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][N:23]=3)[C:12]=2[CH:28]([CH3:29])[CH3:30])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672855824-(6-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-isopropyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 509390794-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-(1-methylethyl)-2-(2-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-isopropyl-2-(pyridin-2-yl)quinoline (30 mg, 0.061 mmol), sodium tert-butoxide (11.73 mg, 0.122 mmol), morpholine (5.85 μL, 0.067 mmol), XPhos (5.82 mg, 0.012 mmol) and Pd2(dba)3 (5.6 mg, 6.11 μmol) in toluene (2.0 mL) and heating at 120° C. in the microwave for 90 min. After purification 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-(1-methylethyl)-2-(2-pyridinyl)quinoline was obtained as a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 8.74 (1H, dd, J=4.9, 2.2 Hz), 7.86-7.93 (1H, m), 7.82 (1H, dd, J=9.8, 2.7 Hz), 7.66 (1H, d, J=7.4 Hz), 7.62 (1H, d, J=2.3 Hz), 7.53 (1H, dd, J=9.4, 5.9 Hz), 7.42 (1H, dd, J=7.4, 3.9 Hz), 7.17-7.25 (1H, m), 5.75 (1H, d, J=2.3 Hz), 3.80-3.93 (2H, m), 3.70-3.78 (4H, m), 3.34-3.48 (1H, m), 2.88-3.04 (4H, m), 1.62 (3H, s), 1.51 (3H, s), 1.29 (3H, d, J=7.0 Hz), 1.23 (3H, d, J=7.0 Hz). Mass Spectrum (ESI) m/e=498 (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-(1-methylethyl)-2-(2-pyridinyl)quinoline
  3. customwas obtained as a yellow oil

Sources & evidence

ORD record
ord-57717dddbfd34342958aafb2e54682a5
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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