Sodium hydride → 2-(2-Methoxy-pyrimidin-4-ylamino)-thiazole-5-carbonitrile

HRID 1241396Notes

Reaction equation

HRID 1241396 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[N:10]=[C:9]([NH2:11])[CH:8]=[CH:7][N:6]=1.Cl[C:13]1[S:14][C:15]([C:18]#[N:19])=[CH:16][N:17]=1>C1COCC1>[CH3:3][O:4][C:5]1[N:10]=[C:9]([NH:11][C:13]2[S:14][C:15]([C:18]#[N:19])=[CH:16][N:17]=2)[CH:8]=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1606792-O-MethylcytosineHCID 14852222-Chlorothiazole-5-carbonitrile

Product 1

HCID 219346202-(2-Methoxy-pyrimidin-4-ylamino)-thiazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A flame dried flask under argon (g) was charged with sodium hydride (33 mg, 60% dispersion, 0.83 mmol) and 1.5 mL anhydrous THF. 2-Methoxy-pyrimidin-4-ylamine (26 mg, 0.21 mmol) was added slowly. After the resulting bubbling ceased, 2-chloro-thiazole-5-carbonitrile (30 mg, 0.21 mmol) was added and the reaction was heated to reflux. After 2 hours, the reaction was cooled to room temperature, the THF was removed in vacuo, and the mixture was diluted with water and adjusted to pH 7 with 1M HCl (aq). The resulting precipitate was filtered, washed with water and air dried. The resulting solid was purified by flash column chromatography (eluted with a gradient 85:15 hexane/EtOAc to EtOAc) to give a pure sample of the title compound. 1H-NMR (300 MHz, DMSO-d6) 12.61 (s, 1H), 8.36 (d, 1H, J=6.4 Hz), 6.73 (d, 1H, J=5.6 Hz), 4.02 (s, 3H). mp>250.

Workup

  1. customA flame dried flask under argon (g)
  2. customAfter the resulting bubbling
  3. temperaturethe reaction was heated to reflux
  4. customthe THF was removed in vacuo
  5. additionthe mixture was diluted with water
  6. filtrationThe resulting precipitate was filtered
  7. washwashed with water and air
  8. customdried
  9. customThe resulting solid was purified by flash column chromatography (
  10. washeluted with a gradient 85:15 hexane/EtOAc to EtOAc)

Sources & evidence

ORD record
ord-71c2775553174c24b528b7d4a05c9ef2
Source dataset
uspto-grants-2006_10
Patent number
US07115597B2

Reaction notes

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