Reacción #160449

Ecuación de reacción

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

Rendimiento 16.1%

Disolventes

DCM

DCM

DCM

DCM

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente