反应详情

732 mg (2.3 mmol) of TBTU and 1 ml (7 mmol) of triethylamine are added to a solution of 408 mg (2.3 mmol) of desamino-histidine hydrochloride in 6 ml of dimethylformamide. After stirring for 10 min, 751 mg (1.8 mmol) of (R)-2-amino-1-(3-but-2-ynyloxy-3-o-tolyl-azetidin-1-yl)-3-(4-methoxyphenyl)propan-1-one in 6 ml of dimethylformamide are added. The reaction medium is stirred for 115 hours at ambient temperature and then a 1N aqueous solution of sodium hydroxide is added and the medium is extracted with a 1/1 heptane/ethyl acetate mixture. The organic phase is dried over sodium sulphate, filtered and concentrated. The residue obtained is purified by silica gel chromatography, elution being carried out with a 90/10 dichloro-methane/methanol mixture. 362 mg of N—[(R)-2-(3-but-2-ynyloxy-3-o-tolylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide are obtained in the form of a white solid with a yield of 40%.

1. stirringThe reaction medium is stirred for 115 hours at ambient temperature
2. extractionthe medium is extracted with a 1/1 heptane/ethyl acetate mixture
3. dry with materialThe organic phase is dried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue obtained
7. customis purified by silica gel chromatography, elution