Sodium hydride → 6-Bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]

HRID 1618490Notes

Reaction equation

HRID 1618490 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]2[NH:8][CH2:9][C:10]3([CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1.Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=2)[N:20]=[C:19]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[C:18]=1[CH3:34].[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[C:6]2[N:8]([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])[CH2:9][C:10]3([CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 582218836-Bromo-1,2-dihydrospiro(indole-3,4'-oxane)HCID 596310754-Chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 672857806-Bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

Prepared according to procedure M using 6-bromo-2′,3′,5′,6′-tetrahydrospiro-[indoline-3,4′-pyran] (98 mg, 367 μmol), 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (100 mg, 367 μmol) in DMF (4.5 mL) and sodium hydride (18 mg, 0.73 mmol) and heating the reaction mixture at 130° C. for 8 h. After purification 6-bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] was obtained as a yellow film. 1H NMR (400 MHz, chloroform-d) δ ppm 8.74 (1H, d, J=5.1 Hz), 7.89-7.98 (2H, m), 7.85 (1H, dd, J=10.0, 2.5 Hz), 7.75 (1H, dd, J=9.2, 6.1 Hz), 7.41 (1H, ddd, J=6.7, 4.5, 2.5 Hz), 7.28-7.33 (1H, m), 7.07 (1H, d, J=7.8 Hz), 6.89 (1H, dd, J=7.8, 2.0 Hz), 6.11 (1H, d, J=2.0 Hz), 3.93-4.10 (4H, m), 3.45-3.60 (2H, m), 2.38 (3H, s), 2.08-2.25 (2H, m), 1.91 (1H, dd, J=13.9, 2.5 Hz), 1.81 (1H, dd, J=13.7, 2.3 Hz). Mass Spectrum (ESI) m/e 504 [(M+1) (79Br)] and 506 [(M+1) (81Br)].

Workup

  1. customPrepared
  2. customAfter purification 6-bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran]
  3. customwas obtained as a yellow film

Sources & evidence

ORD record
ord-69c14360c79c48dcaf4420c26f67beac
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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