N-bromobutanimide → 5'-Bromo-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618767Notes

Reaction equation

HRID 1618767 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([N:28]5[CH2:33][CH2:32][O:31][CH2:30][CH2:29]5)[CH:26]=4)[C:21]4([CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH2:20]3)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[Br:39]N1C(=O)CCC1=O>C(#N)C>[Br:39][C:24]1[N:23]=[C:22]2[C:21]3([CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[CH2:20][N:19]([C:6]3[C:5]4[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=4)[N:9]=[C:8]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=4)[C:7]=3[CH3:18])[C:27]2=[CH:26][C:25]=1[N:28]1[CH2:29][CH2:30][O:31][CH2:32][CH2:33]1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 509390781'-[7-Fluoro-3-Methyl-2-(Pyridin-2-Yl)quinolin-4-Yl]-6'-(Morpholin-4-Yl)-1',2,2',3,5,6-Hexahydrospiro[pyran-4,3'-Pyrrolo[3,2-B]pyridine]

Product 1

HCID 866642805'-Bromo-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of 1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (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 (87 mg, 0.489 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 then it was dried over MgSO4, filtered and evaporated in vacuo to give 5′-bromo-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 8.74 (1H, dt, J=4.8, 1.4 Hz), 7.83-7.99 (3H, m), 7.70 (1H, dd, J=9.2, 5.9 Hz), 7.42 (1H, ddd, J=6.8, 4.7, 2.2 Hz), 7.28-7.34 (1H, m), 5.97 (1H, s), 4.10-4.20 (2H, m), 3.94-4.06 (2H, m), 3.74-3.84 (4H, m), 3.49-3.64 (2H, m), 2.78-2.94 (4H, m), 2.28-2.46 (5H, m), 1.72-1.88 (2H, m). Mass Spectrum (ESI) m/e=590.0 [(M+1) (79Br)] and 592.0 [(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 materialit was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-6c33958e5192496b9df3cd18c213a45a
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…