5-Bromopentanenitrile → HCID 20202803, compound

Participants

Reaction Steps

To a solution of potassium t-butoxide (0.88 g.) in DMF (30 ml.) stirred at 0° under nitrogen was added 4-amino-2-phenylsulphinylmethylpyrimidine (1.84 g.). The solution was stirred for 10 minutes and 5-bromovaleronitrile (1.3 g.) in DMF (5 ml.) added over 5 minutes. The mixture was stirred for 30 minutes at 0°, poured into water (150 ml.) and extracted with EtOAc (4×15 ml.) and the extract dried (MgSO4) and evaporated in vacuo to give a clear gum (1.7 g.). The gum was heated in toluene (40 ml.) at reflux for 30 minutes during which time it was dissolved. The toluene was evaporated in vacuo and the residue partitioned between CH2Cl2 and 1M aqueous hydrochloric acid. The aqueous layer was basified with 4M aqueous sodium hydroxide and extracted with CH2Cl2 (3×15 ml.), the extract dried (MgSO4) and evaporated in vacuo to give a clear gum (900 mg.). To this gum (900 mg.) in acetonitrile (20 ml.) was added 2,2,2-trifluoroethylisothiocyanate (300 mg.) and the solution heated under reflux for 19 hours. The acetonitrile was evaporated in vacuo and trans-6-[4-(3-[2,2,2-trifluoroethyl]thioureido)pyrimid-2-yl]hex-5-enenitrile was isolated from the mixture by medium pressure chromatography on silica using EtOAc/cyclohexane 3:7 v/v as eluant.

Provenance & Evidence