反应 #48796

反应方程式

2-amino-5 methylpyrazine

pyridine

3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid

oxalyl chloride

→

desired compound

收率 98.2%

3-{[(1S)-1-Methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamide

收率 98.2%

溶剂

DCM

DCM

反应条件

后处理

1. 1
   其他the DCM and excess oxalyl chloride evaporated in vacuo
2. 2
   workup.DISSOLUTIONThe residual acid chloride was dissolved in DCM
3. 3
   workup.STIRRINGStirred at ambient temperature for 24 hours
4. 4
   其他The DCM was evaporated in vacuo
5. 5
   其他the residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL)
6. 6
   洗涤The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
7. 7
   干燥dried (MgSO4)
8. 8
   其他evaporated in vacuo
9. 9
   其他The residue was chromatographed on silica
10. 10
    洗涤eluting with a gradient of 30-100% ethyl acetate in isohexane

实验过程

DMF (2 drops) was added to a solution of 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid (6.0 g, 19.0 mmol) and oxalyl chloride (1.99 mL, 22.8 mmol) in DCM (40 mL) The mixture was stirred at ambient temperature for 2 hours and the DCM and excess oxalyl chloride evaporated in vacuo. The residual acid chloride was dissolved in DCM and added dropwise to 2-amino-5 methylpyrazine [Tett lett. 2002, 9287-90] (2.28 g, 19.8 mmol) and pyridine (2.56 mL, 38 mmol) in DCM (40 mL), at 0° C. Stirred at ambient temperature for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL), dried (MgSO4), and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 30-100% ethyl acetate in isohexane, to give the desired compound (7.6 g)

来源