反应详情

To a solution of 2.0 M dimethylamine in THF (5.27 mL, 10.5 mmol) was added a solution of ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.33 g, 1.0 mmol, from Step A) in methylene chloride (5.0 mL). The reaction was stirred at room temperature for 2 hours, then concentrated. The residue was dissolved in tetrahydrofuran (20 mL), water (6 mL) was added, followed by lithium hydroxide monohydrate (0.4 g, 10 mmol). The mixture was stirred for one hour, then was rotovapped to remove most of the THF. The pH was adjusted to 7 by the addition of cone. HCl. Acetonitrile (10 mL) was added, the mixture was filtered and then purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) to afford product as a light yellow solid. Yield: 0.153 g (58%); LC-MS: 250.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 8.02 (s, 1H), 3.70 (s, 2H), 2.27 (s, 6H).

1. concentrationconcentrated
2. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
3. additionwater (6 mL) was added
4. stirringThe mixture was stirred for one hour
5. customto remove most of the THF
6. additionThe pH was adjusted to 7 by the addition of cone
7. additionAcetonitrile (10 mL) was added
8. filtrationthe mixture was filtered
9. custompurified via preparative HPLC-MS (C18
10. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
11. customto afford product as a light yellow solid