Sodium hydride → HCID 12968195, compound

HRID 1531818Notes

Reaction equation

HRID 1531818 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=O)=[CH:5][CH:4]=1.C[O:19][CH:20](OC)[N:21]([CH3:23])C.CN[C:28](=O)[CH2:29][C:30]1[S:31][CH:32]=[C:33]([CH3:35])[N:34]=1.[H-].[Na+]>O1CCCC1.O.CO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:28]=[C:29]([C:30]3[S:31][CH:32]=[C:33]([CH3:35])[N:34]=3)[C:20](=[O:19])[N:21]([CH3:23])[C:10]=2[C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 78373Dimethylformamide dimethyl acetalHCID 10899117HCID 10899117, compoundHCID 18315874HCID 18315874, compound

Product 1

HCID 12968195HCID 12968195, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-methoxyphenyl)-1-(pyrazine-2-yl)ethanone (1.0 g) and dimethylformamide-dimethylacetal (10 cm3) were stirred at room temperature for 18 h. The excess reagent was evaporated under reduced pressure to give an oil. The oil was dissolved in tetrahydrofuran (60 cm3). N-methyl 2-(4-methylthiazol-2-yl)acetamide (0.74 g) and methanol (0.36 cm3) were added followed by sodium hydride (0.42 g). The reaction mixture was stirred at room temperature under nitrogen for 18 h then poured into water (500 cm3) and extracted with diethyl ether (3×150 cm3). The ether extracts were combined, washed with brine dried over magnesium sulphate, filtered and evaporated under reduced pressure to give an oil. The oil was purified by chromatography using dichloromethane (500 cm3), dichloromethane/methanol (99:1, 500 cm3) dichloromethane/methanol (98:2) as eluant. The appropriate fractions were combined and evaporated under reduced pressure to give a foam, which on tritiation with ether gave a solid. The solid was recrystallised from ethyl acetate to give 5-(4-methoxyphenyl)-1-methyl -3-(4-methylthiazol-2-yl)-6-(pyrazin-2-yl)-1H-pyridin-2-one (0.15 g 8%) as a greenish-yellow solid m.p. 168-170° C. (Found: C, 64.48; H, 4.45; N, 14.22. C21H18N4O2S requires C, 64.60; H, 4.65; N, 14.35%); δH (360 MHz; CDCl3) 2.52 (3H, s, ArCH3) 3.53 (3H, s, NMe), 3.74 (3H, s, OCH3) 6.70(2H, d, J 9, methoxyphenyl H-2), 6.92(2H, d, J 9, methoxyphenyl H-2), 7.05 (1H, s, thiazolyl H-4) 8.25 (1H, d, J pyrazine H-), 8.52 (1H, d, J pyrazine H-) 8.72 (2H d J pyrazine H- and 1H, s, pyridone H-4); m/z (ESP+) 391 (MH+).

Workup

  1. customThe excess reagent was evaporated under reduced pressure
  2. customto give an oil
  3. extractionextracted with diethyl ether (3×150 cm3)
  4. washwashed with brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give an oil
  9. customThe oil was purified by chromatography
  10. customevaporated under reduced pressure
  11. customto give a foam, which on tritiation with ether
  12. customgave a solid
  13. customThe solid was recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-cdfafe7d360c4fc89da2717e2d710c1a
Source dataset
uspto-grants-2001_03
Patent number
US06200982B1

Reaction notes

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