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

HRID 1618552Notes

Reaction equation

HRID 1618552 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[NH:27][C:26](=[O:28])[CH:25]=[CH:24][CH:23]=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.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([CH3:31])[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[NH:27][C:26](=[O:28])[CH:25]=[CH:24][CH:23]=3)[C:12]=2[CH3:29])[CH2:9]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 672846726-(4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methylquinolin-2-yl)pyridin-2(1H)-oneHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 509387216-(4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-quinolinyl)-2(1H)-pyridinone

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Prepared according to procedure N using 6-(4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methylquinolin-2-yl)pyridin-2(1H)-one (43.6 mg, 0.091 mmol), morpholine (0.016 mL, 0.18 mmol), Pd2dba3 (12.5 mg, 0.014 mmol), 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (13.0 mg, 0.027 mmol), and sodium tert-butoxide (17.5 mg, 0.18 mmol) in toluene (1.5 mL). The reaction mixture was stirred 100° C. for 18 h. Purification afforded 6-(4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-quinolinyl)-2(1H)-pyridinone as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.72-7.83 (2H, m), 7.65 (1H, d, J=2.7 Hz), 7.50-7.63 (1H, m), 7.29-7.36 (1H, m), 6.80 (2H, d, J=7.0 Hz), 5.68-5.82 (1H, m), 3.82 (2H, s), 3.64-3.78 (4H, m), 2.89-3.05 (4H, m), 2.51 (3H, s), 1.59 (3H, s), 1.55 (3H, s). Mass Spectrum (ESI) m/e=486 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-dd36ccf1d71d41b79b8c55eacc11842d
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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