反应 #160449

反应方程式

3-cyanobenzoyl chloride

Et3N

(S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide

Et3N

→

3-(5-((S)-2-imino-1,4-dimethyl-6-oxo-hexahydropyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)benzonitrile

收率 16.1%

溶剂

DCM

DCM

DCM

DCM

反应条件

后处理

1. 1
   洗涤washed with H2O (10 mL) and saturated brine (10 mL)
2. 2
   浓缩concentrated in vacuo
3. 3
   洗涤washed with H2O (10 mL) and saturated brine (10 mL)
4. 4
   浓缩concentrated in vacuo
5. 5
   workup.ADDITIONThe residue was treated with 30% TFA/DCM (1 mL) at RT for 1 h
6. 6
   浓缩The mixture was concentrated in vacuo
7. 7
   其他the residue was purified on reverse phase HPLC (B)

实验过程

To a solution of (S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide (CY1; R6=Me, 0.037 g, 0.12 mmol) in DCM (0.3 mL) at 0° C. was added Et3N (0.035 mL, 0.24 mmol, 2 eq) followed by 3-cyanobenzoyl chloride (0.027 g, 0.16 mmol, 1.3 eq). The mixture was stirred at RT for 6 h. The mixture was diluted with DCM (20 mL), washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The residue was then treated with TsCI (0.035 g, 0.18 mmol, 1.5 eq), Et3N (0.046 mL, 0.31 mmol, 2.6 eq), and DMAP (0.002 g, 0.016 mmol, 0.13 eq) in DCM (0.25 mL) at RT for 16 h. The mixture was diluted with DCM (20 mL), washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The residue was treated with 30% TFA/DCM (1 mL) at RT for 1 h. The mixture was concentrated in vacuo and the residue was purified on reverse phase HPLC (B) to give 0.006 g (12%) of 3-(5-((S)-2-imino-1,4-dimethyl-6-oxo-hexahydropyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)benzonitrile as a white solid (CZ1; R6=Me). 1HNMR (CD3OD, 300 MHz): 8.49 (m, 2H), 8.12 (d, 1H), 7.92 (t, 1H), 3.75 (m, 2H), 3.36 (s, 3H), 1.82 (s, 3H). MS (ESI): MH+=311.2, HPLC (A) Rt=4.175 min.

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