Sodium hydride → 3-(5,6-Dimethyl-pyridine-3-carbonyl)-1-(2-fluoro-benzyl)-1H-quinolin-4-one

HRID 226929Notes

Reaction equation

HRID 226929 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][CH:12]=2)=[O:10])[CH:5]=[N:6][C:7]=1[CH3:8].[H-].[Na+].[F:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27]Br>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:27][C:26]3[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=3[F:24])[CH:12]=2)=[O:10])[CH:5]=[N:6][C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 577545393-(5,6-Dimethyl-pyridine-3-carbonyl)-1H-quinolin-4-one

Product 1

HCID 577547803-(5,6-Dimethyl-pyridine-3-carbonyl)-1-(2-fluoro-benzyl)-1H-quinolin-4-oneYield 92.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 4g was prepared following the procedure described in Step 3 of Example 1. 63 mg (0.23 mmol) of 3-(5,6-dimethyl-pyridine-3-carbonyl)-1H-quinolin-4-one 3c, 11 mg (0.27 mmol) of 60% sodium hydride and 51 mg (0.27 mmol) of 2-fluorobenzyl bromide were combined in 1 mL N,N-dimethylformamide at rt for 1 h. The product was purified using reverse phase HPLC, mobile phase with a gradient 10-70% acetonitrile in 50 min. The HPLC fractions containing pure product were combined and the combined solutions was lyophilized with 1 mL of 1 M HCl to give 82 mg of a pale yellow solid 4g as its HCl salt: LC-MSD, m/z for C24H19FN2O2 [M+H]+=387.5, HPLC retention time: 1.2 min; 1H NMR (400 MHz, CDCl3): δ 2.55 (s, 3H), 2.9 (s, 3H), 5.55 (s, 2H), 7.05-7.2 (m, 3H), 7.3-7.4 (m, 1H), 7.45-7.55 (m, 2H), 7.65-7.75 (m, 1H), 8.35-8.45 (m, 2H), 8.6 (s, 1H), 8.85 (s, 1H).

Workup

  1. customCompound 4g was prepared
  2. customThe product was purified
  3. customin 50 min
  4. additionThe HPLC fractions containing pure product

Sources & evidence

ORD record
ord-bf9b0c8017394d3090a4cf0ad71b54ca
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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