N-bromobutanimide → 4-(5-bromo-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 1618770Notes

Reaction equation

HRID 1618770 reaction equation
[CH3:1][C:2]1([CH3:35])[C:6]2=[N:7][CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:10]=[C:5]2[N:4]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=3)[N:20]=[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[C:18]=2[CH3:34])[CH2:3]1.C1C(=O)N([Br:43])C(=O)C1>C(#N)C>[Br:43][C:8]1[N:7]=[C:6]2[C:2]([CH3:35])([CH3:1])[CH2:3][N:4]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]=[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:18]=3[CH3:34])[C:5]2=[CH:10][C:9]=1[N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 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

Product 1

HCID 866642814-(5-bromo-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 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of 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 (250 mg, 0.489 mmol) in acetonitrile (6 mL) at 0° C. was added dropwise via syringe over 5 min a solution of n-bromosuccinimide (76 mg, 0.426 mmol) in acetonitrile (4 mL). The reaction was stirred at this temperature for 15 min. After this time the reaction was partitioned between EtOAc (40 mL) and water (15 mL). The separated organic layer was washed with NaHCO3 (15 mL, saturated aqueous solution) and Na2S2O3 (15 mL, saturated aqueous solution) and dried over MgSO4, filtered and evaporated in vacuo to give 4-(5-bromo-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. 1H NMR (400 MHz, chloroform-d) δ ppm 8.64-8.82 (1H, m), 7.85-7.97 (3H, m), 7.75 (1H, dd, J=9.2, 5.9 Hz), 7.40-7.45 (1H, m), 7.31 (1H, ddd, J=9.3, 8.0, 2.6 Hz), 5.97 (1H, s), 3.71-3.90 (6H, m), 2.77-2.94 (4H, m), 2.38 (3H, s), 1.58 (3H, s), 1.52 (3H, s). Mass Spectrum (ESI) m/e=548.0 [(M+1) (79Br)] and 550.0 [(M+1) (81Br)]

Workup

  1. customAfter this time the reaction was partitioned between EtOAc (40 mL) and water (15 mL)
  2. washThe separated organic layer was washed with NaHCO3 (15 mL, saturated aqueous solution) and Na2S2O3 (15 mL, saturated aqueous solution)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-f825b2078bb9472e962cec21cd62b82d
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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