Tetrahydrofuran → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-7-fluoro-1H-quinolin-4-one

HRID 226967Notes

Reaction equation

HRID 226967 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][C:12]([F:18])=[CH:13][CH:14]=2)[NH:9][CH:8]=1)=[O:6].[CH3:23][Si](C)(C)[N-][Si](C)(C)C.[K+].[Br:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40]Br)[N:35]=1.O1[CH2:46][CH2:45][CH2:44][CH2:43]1>>[Br:33][C:34]1[N:35]=[C:36]([CH2:40][N:9]2[C:10]3[C:15](=[CH:14][CH:13]=[C:12]([F:18])[CH:11]=3)[C:16](=[O:17])[C:7]([C:5](=[O:6])[C:4]3[CH:19]=[CH:20][C:21]([CH3:22])=[C:2]([CH3:1])[CH:3]=3)=[CH:8]2)[CH:37]=[CH:38][CH:39]=1.[CH3:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][C:12]([F:18])=[CH:13][CH:14]=2)[N:9]([CH2:43][C:44]2[CH:40]=[CH:36][CH:37]=[C:46]([CH3:23])[CH:45]=2)[CH:8]=1)=[O:6]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 3251421Potassium bis(trimethylsilyl)amideHCID 129547962-Bromo-6-(bromomethyl)pyridineHCID 577547943-(3,4-dimethyl-benzoyl)-7-fluoro-1H-quinolin-4-one

Product 2

HCID 577546621-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-7-fluoro-1H-quinolin-4-oneHCID 866136483-(3,4-Dimethyl-benzoyl)-7-fluoro-1-(3-methyl-benzyl)-1H-quinolin-4-one

Conditions

Temperature
60 °C

Procedure

Compound 4vv was prepared following the procedure described in Step 3 of Example 1 using 0.050 g (0.169 mmol) of 3-(3,4-dimethyl-benzoyl)-7-fluoro-1H-quinolin-4-one 3k, 0.4 mL of potassium hexamethyldisilazide (0.5 M in toluene, 0.203 mmol) and 50.9 mg (0.203 mmol) of 2-bromo-6-bromomethyl-pyridine in 1.5 mL of tetrahydrofuran and heating the reaction solution at 60° C. for 24 h. The crude product was purified by flash chromatography using 10-80% ethyl acetate in hexane to yield 37.8 mg of 3-(3,4-Dimethyl-benzoyl)-7-fluoro-1-(3-methyl-benzyl)-1H-quinolin-4-one 4vv as a white solid: LC-MSD, m/z for C24H18BrFN2O2 [M+H]: 465.4, 466.5, 467.4, 468.4; Reverse phase HPLC gradient, 20-95% acetonitrile with 0.1% TFA in 4 minutes, retention time=2.8 min; 1H NMR (400 MHz, CDCl3): δ 8.47 (1H, m), 8.23 (1H, s), 7.64 (1H, s), 7.56 (1H, m), 7.53 (1H, m), 7.47 (1H, m), 7.18 (1H, m), 7.12 (1H, m), 7.05-7.02 (2H, m), 5.39 (2H, s), 2.32 (3H, s), 2.31 (3H, s).

Workup

  1. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-cda8ac65682f44b886f2531f2944b6cc
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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