تفاعل #82287

معادلة التفاعل

3-(5-amidinobenzo[b]thien-2-yl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionic acid dihydrochloride

ethyl (N-methyl)acetimidate hydrochloride

sodium hydroxide

→

title compound

المردود 33.2%

3-(5-amidinobenzo[b]thien-2-yl)-2-[4-[[(3S)-1-(N-methyl-acetimidoyl)-3-pyrrolidinyl]oxy]phenyl]propionic acid dihydrochloride

المردود 33.2%

المذيبات

water

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىhas been prepared in accordance with the procedure
2. 2
   workup.DISTILLATIONAfter distilling off the solvent
3. 3
   غسيلthe resulting residue was washed with dichloromethane
4. 4
   تركيزconcentrated to dryness

الإجراء التجريبي

2.0 g of 3-(5-amidinobenzo[b]thien-2-yl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionic acid dihydrochloride was dissolved in a solvent mixture of 10 ml of water and 10 ml of acetonitrile. With stirring, to the thus prepared solution was gradually added 20 g of ethyl (N-methyl)acetimidate hydrochloride which has been prepared in accordance with the procedure disclosed in The Journal of Organic Chemistry (vol.33, pp.1679-1681, 1968), while maintaining the pH level of the solution at 8.5 with 2N sodium hydroxide aqueous solution. After distilling off the solvent, the resulting residue was washed with dichloromethane and then subjected to column chromatography using a column packed with a highly porous polymer type synthetic adsorbent (styrene-divinylbenzene polymer: Diaion HP-20) and using a water/acetonitrile mixture as an elution solvent, thereby effecting desalting. Fractions of interest thus pooled were subjected to reversed phase high performance liquid chromatography using a column packed with octadecyl-bonded silica gel. Thereafter, the thus eluted fractions of interest were pooled and then concentrated to dryness by passing through a C1 type of strongly basic ion exchange resin (Diaion SA-10, Nippon Rensui Co., Ltd.). In this way, 370 mg of the title compound was obtained in a solid form.

المصدر