Cesium carbonate → Tert-butyl 4-(5-cyano-1,3-benzothiazol-2-yl)-3-oxopiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a flask charged with 2-chloro-1,3-benzothiazole-5-carbonitrile [prepared from 3-amino-4-chlorobenzonitrile following the procedure described in US Publication 2009/0197862, Example 267] (146 mg, 0.75 mmol) and a stir bar was added tert-butyl 3-oxopiperazine-1-carboxylate (225 mg, 1.1 mmol), Pd2(dba)3 (69 mg, 0.075 mmol), Xantphos (87 mg, 0.15 mmol), cesium carbonate (370 mg, 1.1 mmol), and dioxane (10 mL). The mixture was purged three times with nitrogen, and heated to 100° C. under N2 for 16 hours. The reaction was diluted with EtOAc, adsorbed onto silica gel, and purified by silica gel chromatography (Hexanes:EtOAc 1:1) to provide tert-butyl 4-(5-cyano-1,3-benzothiazol-2-yl)-3-oxopiperazine-1-carboxylate (95 mg, 35% yield). The carboxylate was further treated with TFA to remove the Boc group. After removal of TFA, the residue was dissolved in aqueous sodium carbonate, extracted with DCM, dried over sodium sulfate, and concentrated to provide the free base of 2-(2-oxopiperazin-1-yl)-1,3-benzothiazole-5-carbonitrile. LC-MS (IE, m/z): 259 [M+1]+.

Provenance & Evidence