Sodium hydride → 1-(6-bromo-pyridin-2-ylmethyl)-3-(5,6-dimethyl-pyridine-2-carbonyl)-1H-quinolin-4-one

HRID 226968Notes

Reaction equation

HRID 226968 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([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])=[N:6][C:7]=1[CH3:8].[H-].[Na+].[Br:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31]Br)[N:26]=1>CN(C)C=O>[Br:24][C:25]1[N:26]=[C:27]([CH2:31][N:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20](=[O:21])[C:11]([C:9]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[C:7]([CH3:8])[N:6]=3)=[O:10])=[CH:12]2)[CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 129547962-Bromo-6-(bromomethyl)pyridineHCID 577545223-(5,6-Dimethyl-pyridine-2-carbonyl)-1H-quinolin-4-one

Product 1

HCID 577546441-(6-bromo-pyridin-2-ylmethyl)-3-(5,6-dimethyl-pyridine-2-carbonyl)-1H-quinolin-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 4ww was prepared following the procedure described in Step 3 of Example using 45 mg (0.16 mmol) of 3-(5,6-dimethyl-pyridine-2-carbonyl)-1H-quinolin-4-one 3d, 8 mg (0.21 mmol) of 60% sodium hydride and 53 mg (0.21 mmol) of 2-bromo-6-bromomethyl-pyridine in 0.7 mL N,N-dimethylformamide and stirring the reaction mixture at rt for 2 h. The product was purified using reverse phase HPLC (mobile phase with a gradient 10-50% acetonitrile in 50 min). The HPLC fractions containing pure product were combined, evaporated under vacuum and neutralized using methanolic ammonia and purified by flash chromatography (using 30-100% ethyl acetate in hexane) to give 18 mg of a pale yellow solid: LC-MSD, m/z for C23H18BrN3O2 [M+H]+: 448.4, 450.4; Reverse phase HPLC gradient, 20-95% acetonitrile with 0.1% TFA in 4 minutes, retention time=2.1 min; 1H NMR (400 MHz, CDCl3): δ 2.35 (s, 3H), 2.5 (s, 3H), 5.5 (s, 2H), 7.0-7.1 (m, 1H), 7.3-7.35 (m, 1H), 7.35-7.4 (m, 1H), 7.4-7.6 (m, 4H), 7.6-7.7 (m, 1H), 8.4-8.45 (m, 1H), 8.5 (s, 1H).

Workup

  1. customThe product was purified
  2. customin 50 min
  3. additionThe HPLC fractions containing pure product
  4. customevaporated under vacuum
  5. custompurified by flash chromatography (using 30-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0de758828ff34b2dbf8df13f21fec561
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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