Sodium hydride → 2-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamino]-thiazole-5-carbonitrile

HRID 1355451Notes

Reaction equation

HRID 1355451 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:16])([CH3:15])[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH2:14])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:20]1[S:21][C:22]([C:25]#[N:26])=[CH:23][N:24]=1>C1COCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:16])([CH3:15])[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:20]2[S:21][C:22]([C:25]#[N:26])=[CH:23][N:24]=2)[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14852222-Chlorothiazole-5-carbonitrileHCID 918651944-(2-Tert-butylsilyloxypropan-2-yl)pyridin-2-amine

Product 1

HCID 1317239462-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamino]-thiazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(tert-Butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (8-5, 5.94 g, 24.9 mmol) was dissolved in 50 mL anhydrous THF under N2. NaH (60% suspension, 2.99 g, 74.8 mmol, 3 equiv) was added (vigorous bubbling occurs) and the resulting mixture was stirred for 15 min. 2-Chloro-thiazole-5-carbonitrile (4.32 g, 29.9 mmol) was added and the reaction was heated to reflux. After 2 h the reaction was cooled and was quenched by the addition of water. The THF was removed in vacuo and the resulting aqueous solution was adjusted to pH=7 by the addition of 1M HCl (aq). The resulting precipitate was filtered and washed with water to provide reasonably pure desired product. 1H NMR (CDCl3) δ10.32 (bs, 1H), 8.33 (d, 1H, J=5.3 Hz), 7.99 (s, 1H), 6.96 (s, 1H), 6.91 (d, 1H, J=5.3 Hz), 4.78 (s, 2H), 0.98 (s, 9H), 0.16 (s, 6H)

Workup

  1. custom(vigorous bubbling occurs)
  2. temperaturethe reaction was heated to reflux
  3. temperatureAfter 2 h the reaction was cooled
  4. customwas quenched by the addition of water
  5. customThe THF was removed in vacuo
  6. additionthe resulting aqueous solution was adjusted to pH=7 by the addition of 1M HCl (aq)
  7. filtrationThe resulting precipitate was filtered
  8. washwashed with water

Sources & evidence

ORD record
ord-73d5957cc445405fb7ff3e18605a95aa
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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