반응 #440645

반응 방정식

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

수율 35.7%

용매

dichloromethane methanol

ethyl acetate

반응 조건

후처리

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

실험 절차

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.

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