Acetonitrile → Sodium 3-cyano-1-(2,6-difluorophenyl)-6-oxo-1,6-dihydropyridine-2-thiolate

HRID 1713070Notes

Reaction equation

HRID 1713070 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+:10].[C:11](#[N:13])[CH3:12].[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[N:22]=[C:23]=[S:24].CN1[CH:33]=[CH:32][C:30](=[O:31])N(C)C1=O>C1COCC1.CCO>[C:11]([C:12]1[CH:33]=[CH:32][C:30](=[O:31])[N:22]([C:16]2[C:15]([F:14])=[CH:20][CH:19]=[CH:18][C:17]=2[F:21])[C:23]=1[S-:24])#[N:13].[Na+:10]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 701221,3-DimethyluracilHCID 2724254Sodium bis(trimethylsilyl)amideHCID 40316012,6-Difluorophenyl isothiocyanate

Product 1

HCID 67533031Sodium 3-cyano-1-(2,6-difluorophenyl)-6-oxo-1,6-dihydropyridine-2-thiolateYield 86%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of sodium bis(trimethylsilyl)amide (351 ml of a 1M solution in THF, 351 mmol) in THF (150 ml) was cooled to −78° C. and acetonitrile (30 ml) was added. After 20 min, 2,6-difluorophenyl isothiocyanate (30.0 g, 175.5 mmol) was added slowly over 5 min. The reaction mixture was allowed to warm slowly to r.t. over 2 h. EtOH (100 ml) was added followed by 1,3-dimethyluracil (27.0 g, 193.5 mmol) and the mixture heated to reflux for 18 h. After cooling, the mixture was concentrated in vacuo to a volume of approx. 150 ml and EtOH (75 ml) was added. This mixture was cooled and Et2O (approx. 750 ml) was added slowly to give a pale yellow precipitate. The solid was filtered off, washed with Et2O (2×100 ml) then dried to give the title compound as a yellow/pale brown solid (49.0 g, 86%). δH (DMSO-d6) 7.43-7.33 (1H, m), 7.23 (1H, d, J 9.2 Hz), 7.13-7.06 (2H, m), 5.64 (1H, d, J 9.2 Hz). LCMS (ES+) RT 7.0 minutes, 265 (M+H)+.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 18 h
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated in vacuo to a volume of approx. 150 ml and EtOH (75 ml)
  5. additionwas added
  6. temperatureThis mixture was cooled
  7. additionEt2O (approx. 750 ml) was added slowly
  8. customto give a pale yellow precipitate
  9. filtrationThe solid was filtered off
  10. washwashed with Et2O (2×100 ml)
  11. customthen dried

Sources & evidence

ORD record
ord-d0e14174ee5e487684b436a1485f823c
Source dataset
uspto-grants-2010_09
Patent number
US07795256B2

Reaction notes

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