Sodium hydride → HCID 12968195, compound

HRID 275761Notes

Reaction equation

HRID 275761 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 rea,ent 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 (3×50 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 (360MHz; 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 rea,ent was evaporated under reduced pressure
  2. customto give an oil
  3. extractionextracted with diethyl ether (3×50 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-9aad33e83f424bdb912ec7920e6a3522
Source dataset
uspto-grants-2002_03
Patent number
US06352994B2

Reaction notes

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