Hydrochloric Acid → 2-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-3-methyl-pyridin-2-ylamino]-thiazole-5-carbonitrile
Reaction equation
[H-].[Na+].[C:3]([SiH2:7][O:8][C:9]([CH3:19])([CH3:18])[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[C:11]=1[CH3:17])([CH3:6])([CH3:5])[CH3:4].Cl[C:21]1[S:22][C:23]([C:26]#[N:27])=[CH:24][N:25]=1.Cl>O.C1COCC1>[C:3]([SiH2:7][O:8][C:9]([CH3:19])([CH3:18])[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:21]2[S:22][C:23]([C:26]#[N:27])=[CH:24][N:25]=2)[C:11]=1[CH3:17])([CH3:6])([CH3:5])[CH3:4]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
An oven dried flask under N2 was charged with NaH (60% dispersion, 210 mg, 5.25 mmol). 5 mL of anhydrous THF was added followed by 4-(tert-butyl-dimethyl-silanyloxymethyl)-3-methyl-pyridin-2-ylamine (10-2, 0.602 g, 2.39 mmol) and 2-chloro-5-cyanothiazole (1-2, 0.414 g, 2.86 mmol). The resulting solution was heated to reflux. After 19 hours additional NaH (19 mg, 0.48 mmol) and 2-chloro-5-cyanothiazole (1-2, 0.069 g, 0.48 mmol) were added. After an additional 1 hour at reflux the reaction was allowed to cool to room temperature and diluted with water. The pH was adjusted to 7 with 1 M HCl. The resulting precipitate was filtered and washed with water to afford 10-3. 1H NMR (CDCl3) δ 8.41 (bs, 1H), 8.27 (d, 1H, J=5.2 Hz), 7.94 (s, 1H), 7.19 (d, 1H, J=5.2 Hz), 4.74 (s, 2H), 2.21 (s, 3H), 0.96 (s, 9H), 0.13 (s, 6H).
Workup
- customAn oven dried flask under N2
- temperatureThe resulting solution was heated to reflux
- temperatureAfter an additional 1 hour at reflux the reaction
- filtrationThe resulting precipitate was filtered
- washwashed with water
- customto afford 10-3
Sources & evidence
- ORD record
- ord-887d37eea62842929e0b7f574d0cdbd2
- Source dataset
- uspto-grants-2005_04
- Patent number
- US06875767B2
Reaction notes
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