تفاعل #440645

معادلة التفاعل

1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-(t-butyloxycarbonyl)piperazine

hydrogen chloride

4-(4-pyridyl)benzoic acid

triethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-[4-(4-pyridyl)benzoyl]piperazine

المردود 35.7%

المذيبات

dichloromethane methanol

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent was removed in vacuo
2. 2
   أخرىthe residue dried under high vacuum
3. 3
   workup.STIRRINGAfter stirring overnight the solvent
4. 4
   أخرىwas removed in vacuo
5. 5
   غسيلThis was washed sequentially with water, saturated sodium bicarbonate solution, water and brine
6. 6
   أخرىEvaporation of the solvent
7. 7
   أخرىgave a residue which
8. 8
   أخرىwas purified by chromatography (MPLC on Merck Art 9385 silica, gradient eluting with ethyl acetate containing 0-8.0% methanol)

الإجراء التجريبي

A solution of 1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-(t-butyloxycarbonyl)piperazine (860 mg, 2.15 mmol) in dichloromethane/methanol (15 ml of 1:1) was treated with an excess of hydrogen chloride gas as a saturated solution in ethyl acetate. After stirring for 4 hrs. the solvent was removed in vacuo and the residue dried under high vacuum. This was then suspended in DMF and treated sequentially with 4-(4-pyridyl)benzoic acid (428 mg, 2.15 mmol), triethylamine (0.6 ml, 4.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC, 495 mg, 2.68 mmol). After stirring overnight the solvent was removed in vacuo and the residue taken up in dichloromethane (50 ml). This was washed sequentially with water, saturated sodium bicarbonate solution, water and brine. Evaporation of the solvent gave a residue which was purified by chromatography (MPLC on Merck Art 9385 silica, gradient eluting with ethyl acetate containing 0-8.0% methanol) to give 1-(5-chlorobenzimidazol-2-ylsulphonyl)-4-[4-(4-pyridyl)benzoyl]piperazine as colourless crystals (370 mg) from ethanol, m.p. 242-244° C., 1H NMR (d6DMSO) 3.0-3.4 ppm (broad s, 4H), 3.4-3.8 ppm (broad s, 4H), 7.4 ppm (d, 1H), 7.5 ppm (d, 2H), 7.6-7.8 ppm (m, 4H), 7.85 ppm 2H), 8.6 ppm (d, 2H), 14.0 ppm (broad s, 1H); MS (M+H)+ 482/484.

المصدر