Sodium hydride → N-Benzyl-4-methyl-2-(2-oxo-4-(pyridin-3-ylmethoxy)pyridin-1(2H)-yl)thiazole-5-carboxamide

HRID 1887307Notes

Reaction equation

HRID 1887307 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]2=[O:23])=[N:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br.Br[CH2:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:29][C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)=[CH:18][C:17]2=[O:23])=[N:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 127070373-(Bromomethyl)pyridine hydrobromideHCID 54742338N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide

Product 1

HCID 24985612N-Benzyl-4-methyl-2-(2-oxo-4-(pyridin-3-ylmethoxy)pyridin-1(2H)-yl)thiazole-5-carboxamideYield 14.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide (0.10 g, 0.29 mmol) in N,N-dimethylformamide (4 mL) was added sodium hydride (60% dispersion in mineral oil, 0.028 g, 0.70 mmol) slowly at 0° C. The reaction mixture was stirred for 5 minutes and then 3-(bromomethyl)pyridine hydrobromide (0.096 g, 0.38 mmol) and tetra-n-butylammonium iodide (0.005 g, 0.014 mmol) were added at 0° C. After stirred at ambient temperature for 16 hours, the reaction mixture was concentrated in vacuo to yield a solid residue. The crude product was purified by column chromatography eluted with ethyl acetate/hexanes (50/50 to 100/0) to afford the title compound as a white solid (0.018 g, 14% yield): mp 214-216° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.81-8.61 (m, 4H), 7.98 (d, J=7.8 Hz, 1H), 7.55-7.51 (m, 1H), 7.33-7.19 (m, 5H), 6.42-6.39 (m, 1H), 6.28 (d, J=2.7 Hz, 1H), 5.25 (s, 2H), 5.39 (d, J=5.7 Hz, 2H), 2.55 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 167.3, 161.9, 161.6, 153.9, 150.3, 149.1, 148.7, 139.9, 137.8, 132.3, 128.8, 127.7, 127.2, 124.7, 123.8, 104.3, 97.7, 68.3, 17.5; MS (ES+) m/z 433.2 (M+1).

Workup

  1. stirringAfter stirred at ambient temperature for 16 hours
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customto yield a solid residue
  4. customThe crude product was purified by column chromatography
  5. washeluted with ethyl acetate/hexanes (50/50 to 100/0)

Sources & evidence

ORD record
ord-4a574f68a94e4acc8736c9394872ccbd
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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