РЕНО Дэниэл С. (US),СТЭНФОРД Кэтрин Мари (US),ВЛАХОВ Ионтчо Радославов (US)
申请号：
RU2012154914/13
公开号：
RU2012154914A
申请日:
2011.05.19
申请国别(地区):
RU
年份:
2014
代理人:
摘要：
1. A method for producing EC145, comprising the step of treating a compound of the formula: with a compound of the formula: wherein X is alkylsulfonyl, arylsulfonyl, arylthio or heteroarylthio, in the presence of an aqueous buffer with a pH of less than 8.2. The method of claim 1, wherein X is 2-thiopyridinyl or 3-nitro-2-thiopyridinyl. 3. The method of claim 1, wherein X is 2-thiopyridinyl. 4. The method according to any one of claims 1 to 3, where the buffer has a pH of from 5.9 to 6.3.5. The method according to claim 4, where the buffer has a pH of from 5.9 to 6.1.6. The method of claim 1, wherein the buffer is a phosphate buffer. The method of claim 6, wherein the buffer is a sodium phosphate buffer. The method according to claim 1, comprising the step of treating a compound of the formula: with a compound of the formula: in the presence of sodium phosphate buffer having a pH of from 5.9 to 6.3.9. The method of claim 8, wherein the treatment takes place in a liquid medium containing acetonitrile. The method according to claim 1, further comprising the step of treating deacetylvinoblastin hydrazide with an acylating agent of the formula: Y — CO — O— (CH) —SX or an acid addition salt thereof, wherein Y is a leaving group to form a reaction mixture containing a compound of the formula: and directly treating the compound of formula: with a reaction mixture without isolating the compound of formula: 11. The method of claim 10, wherein the acylating agent has the formula: or an acid addition salt thereof. The method of claim 11, wherein the acylating agent has the formula: and is administered in the form of an acid addition salt. The method of claim 11, wherein the acylating agent has the formula: and is administered in the form of a free base. The method according to any one of claims 10 to 13, wherein the deacetylvinoblastinhydrazide is treated with an acylating agent in a solvent containing acetonitrile. The method of claim 10, where deacetyl1. Способ получения EC1
