반응 #160449

반응 방정식

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

수율 16.1%

용매

DCM

DCM

DCM

DCM

반응 조건

후처리

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

실험 절차

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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