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-pyridinyl)quinoline

HRID 1618510Notes

Reaction equation

HRID 1618510 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[CH3:28])[CH2:9][C:8]([CH3:30])([CH3:29])[C:5]2=[N:6][CH:7]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1.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]>[CH3:29][C:8]1([CH3:30])[C:5]2=[N:6][CH:7]=[C:2]([N:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]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[CH3:28])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672855904-(6-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 509393384-(3,3-Dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

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-(pyridin-2-yl)quinoline (75 mg, 0.162 mmol), Pd2dba3 (3.8 mg, 0.016 mmol), XPhos (15.4 mg, 0.032 mmol), morpholine (1.6.9 mL, 0.194 mmol) and sodium tert-butoxide (31.1 mg, 0.324 mmol) in toluene (6 mL). 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-pyridinyl)quinoline was obtained as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.70-8.77 (1H, m), 7.75-7.96 (4H, m), 7.60 (1H, d, J=2.7 Hz), 7.41 (1H, ddd, J=7.1, 5.0, 1.6 Hz), 7.30 (1H, ddd, J=9.1, 8.1, 2.7 Hz), 5.83 (1H, d, J=2.3 Hz), 3.82 (2H, s), 3.69-3.77 (4H, m), 2.91-3.06 (4H, m), 2.38 (3H, s), 1.57-1.64 (3H, m), 1.50-1.56 (3H, m). Mass Spectrum (ESI) m/e=470 (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-pyridinyl)quinoline
  3. customwas obtained as a yellow solid

Sources & evidence

ORD record
ord-d7c201895c694d3a9d12cd655b58b94a
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…