• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a new process for the preparation of 6 alpha -halo-3-keto- DELTA 1,4-pregnadiene-derivatives in two-steps-synthesis affording directly 6 alpha -halo-derivatives by reacting 3-keto-9 beta ,11 beta -oxido- DELTA 1,4-pregnadiene-derivatives with a suitable acylating or etherifying agent to give the corresponding new 3-enol-derivatives which are finally halogenated by using a suitable halogenating agent.
    公开号:SU993823A3
    申请号:SU792764698
    申请日:1979-04-27
    公开日:1983-01-30
    发明作者:Паоло Кастелли Пьер；Романо Бруно
    申请人:Блазинаким С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    (5) METHOD OF OBTAINED DERIVATIVES
    6-GALO-3-KETO-D-PREGNADIENA
    The invention relates to a method I for the preparation of the known 6-halo-3-keto-A-prenadiene derivatives of the general formula.
    LI
    where R and Z is hydrogen, hydroxyl or
    acetoxy W - hydrogen, hydroxyl or
    methyl;
    or Z and W together –ci-oriented group
    -
    - 0 CHj
    X - halogen.
    which are intermediate products in the synthesis of pharmaceuticals.
     A method of producing 6-halo-3-keto-D -pregnadienes of general formula I, which consists in the fact that bromhydrin of the general formula
    ten
    BUT
    15
    Where R, Z and W are as defined above,
    reacted with anhydrous sodium acetate in acetone with
    20 boiling point tl.
    权利要求:
    Claims (2)
    [1]
    The disadvantage of this method is the relatively low availability of the starting compound, due to the difficulty of administering with hydroxychloylfluoride in accordance with the method described in Example Id. 3, g of 6c-fluoro-9 / Pr-oxide. -17oL, 21-dioxypregna-1, -diene-3 | 20-dione, 17,21-diacetate are obtained. T. pl. 224 ° C (decomposition). max nm (е 15300) dLlD +2, (dioxane). Example 3.12 g 9p, 11 / -oxid-1 boC-methyl-17of, 21 - dioxypreg-1D-dien-3, 20-dione is treated as described in example
    [2]
    2. With 6L-fluoro-9p-11p-oxide-1bo-methyl-17ot, 21-dioxy-pregna-1, 4-diene-3,20-dione, 17,21-diacetate (8.7 g) is suspended in a mixture methylene chloride and methanol and treated in a stream of nitrogen with a catalytic amount of methanol potassium hydroxide at room temperature for 90 minutes. After not being neutralized with aqueous acetic acid, the solution is concentrated under reduced pressure and the residue is crystallized from methanol. 6.5 g of bcc-fluoro-9 are obtained (b, 11p-oxide-1bo-methyl-17 "3, 21-dioxypregna-1, -dien-3,20-dione. Mp. 268 ° C (with decomposition .). 2. nm (e 16150) cLljj. + 31C (MG) Example 2 g of the 6-1 fluoro derivative obtained in Example It is added dropwise 10 ml of aqueous hydrobromic acid, which has been pre-cooled to -5 ° C with a strong The mixture is left to stand for about 2 hours at and then carefully poured into an excess of ice-cold sodium carbonate solution. After extraction with methylene chloride and crystallization in a mixture of methylene chloride and methanol, 2.15 g of 6O-fluoro-9o -b is obtained. rum-11 / i, 16 / b, 17cit, 21 -tetrahydroxypregna 1, -diene-3,20-dion-1b, 17a-acetonide 21-acetate. mp. 218 ° С (decomposed) СССЗЗ-р- +106 , (dioxane) LIS nm (e U600) Example 5. a) To suspension 9 /, 1 lp-oxide-I6ct, 17ct, 21-trioxypregna-1, the -dcd-gradient dione 16,17-acetonide 21-acetate (10 g) in tetrahydrofuran (50 ml) methyl methyl formate (10 ml) and absolute methanol (20 ml), p-toluo sulphonic acid (400 mg) are added, the mixture is stirred at room temperature for 6 hours. Pyridine (1 And the solution is distilled under reduced pressure. The remainder of the rice t alla from the comfort of methanol, get 5 g of Z-methoxy-9 | , 11 (L-oxide-1bc, 17ot, 21-trioxypregna-1, 3.5 triene-20-one-1b, 17 acetonide 21-acetate. T pl. "Max 250 nm and 320 nm (E 2900 and 150, respectively ) tcAlj) (dioxane) 5) Perchloride fluoride bubbles are added to a solution of this compound (Wg) in pyridine (60 ml) for 10 minutes. After removing the excess reagent by passing nitrogen bubbles, the solution is poured into ice-cold water. The crystalline solid is filtered, washed well with water, dried and crystallized from methanol. 2 g of 6c are obtained (gfluoro-9p, 1 lfi-oxide-16cL, 7ot, 21-trioxypregna-1, A-diene-3, 20-dione-1b, 17 acetonide 21-acetate. C) Solution of 2 g Zmetil-enol the ester obtained in paragraph in acetone (0 ml) is treated with anhydrous sodium acetate (O, g), water (6 ml) and N-chlorosuccinimidrm (g). The mixture was stirred overnight and the mixture was poured into ice water. The precipitate is collected, washed with water, dried and triturated with methanol to give 1.5 g of 6O1-chloro-9p, 11 / Zgöksido-16ct, 17o, 21-trioxypreg-1, -diene-3,20-dione 16,17-acetonide 21-acetate. T. pl. 199 ° C. .2k7 nm (€) +53 (dioxane). EXAMPLE 6. As described in Example 5a, 21-acetate 9 / b, Ir-oxide-1b "(.-Methyl-21-hydroxypreg-1,4-diene-3, 20-dione is treated with methyl ortho). After the majority of the solvent was removed in vacuo, the residue was dissolved in pyridine and treated with perchlorylfluoride, as described in Example 5ef, 6o1-fluoro-9,11-oxydio-16c | 1. diene-3, 20-dione 21-acetate, mp 178 ° C. toLJjj-i-87 (dioxane) Example 7. Using the procedure of Example 2 and starting from 9 / i, 11p-oxide-16 (i-methyl -17OB-hydroxypregne-1, dien-3, 20-dione (5 g), get 3.5 g 17-acetate 6o.-fluoro-9/5 $ 11-oxide-1br-methyl-176-oxy pregna-1, -diene-3,20-dione. Td Square (decomposed) L |, yes 246 nm (€ 15,000), .JKC ii4e nm and 3 441.2 ° (dioxane) The invention The method of obtaining derivatives 6 Lo-Zketo L is pregnadiene of the general formula where R and Z are hydrogen, hydroxyyl acetoxy, W is hydrogen, hydroxyl yl methyl; or Z and W together are (L-orientation to the group X is halogen, which differs in that, in order to simplify the process, A compound of the general formula where R, Z and W have the indicated meanings, is reacted with an esterifying agent such as isopropenyl acetate or a trialkyl orthoformate in the presence of an acidic acid. alizat (Era, such as p-toluenesulfonic acid, and the resulting compound of general formula dodHzR -.- Z wherein R, Z and W are as defined above; R is lower alkyl, is treated with a halogenating agent, such as N-halo-amide or perchlorylfluoride, followed by isolation of the desired product. Sources of information taken into account in the examination 1. US Patent ff, cl. 260-239.56, publ. 196.
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    同族专利:
    公开号 | 公开日
    ZA791977B|1980-06-25|
    NL187533B|1991-06-03|
    DK173379A|1979-10-29|
    PL117180B1|1981-07-31|
    SE433083B|1984-05-07|
    NL7903413A|1979-10-30|
    NO153431B|1985-12-09|
    DE2916889C2|1985-11-28|
    AT367772B|1982-07-26|
    NO791440L|1979-10-30|
    PL215209A1|1980-01-28|
    CH639981A5|1983-12-15|
    IE790869L|1979-10-28|
    BE875939A|1979-08-16|
    NL187533C|1991-11-01|
    IE48329B1|1984-12-12|
    ES479974A1|1980-09-01|
    AU4645579A|1979-11-01|
    NO153431C|1986-03-19|
    FR2424286B1|1986-01-17|
    JPS591720B2|1984-01-13|
    FR2424286A1|1979-11-23|
    JPS54157554A|1979-12-12|
    GR65300B|1980-08-01|
    GB2019848A|1979-11-07|
    PT69558A|1979-05-01|
    US4188322A|1980-02-12|
    CA1159049A|1983-12-20|
    HU180678B|1983-04-29|
    ATA311179A|1981-12-15|
    GB2019848B|1983-01-26|
    AU518893B2|1981-10-22|
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    引用文献:
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    US3465011A|1966-11-09|1969-09-02|American Home Prod|11-oxygenated-8-iso steroids|
    US3513160A|1968-02-01|1970-05-19|American Home Prod|Process for the preparation of 9alpha-bromo-11beta - hydroxy - 17alpha,20;20,21-bisalkylenedioxy pregnanes|
    NL187577C|1978-04-05|1991-11-18|Sibla Srl|3-ACETOXY-9BETA, 11BETA-EPOXY-PREGNA-1,3,5-TRIEN, PROCESS FOR THE PREPARATION THEREOF, AND PROCESS FOR THE PREPARATION OF 6-alpha-halogen-1,4-diene-3-ones.|
    JPS6363555B2|1978-04-05|1988-12-07|Prochem Ets|NL187577C|1978-04-05|1991-11-18|Sibla Srl|3-ACETOXY-9BETA, 11BETA-EPOXY-PREGNA-1,3,5-TRIEN, PROCESS FOR THE PREPARATION THEREOF, AND PROCESS FOR THE PREPARATION OF 6-alpha-halogen-1,4-diene-3-ones.|
    US4287129A|1980-07-28|1981-09-01|Diamond Shamrock Corp.|Synthesis of 1α-hydroxy-7-dehydrosteroids|
    US4383947A|1981-07-24|1983-05-17|The Upjohn Company|Introduction of a fluorine atom|
    JPS6185637U|1984-11-09|1986-06-05|
    JPH0264662U|1988-11-02|1990-05-15|
    FR2701262B1|1993-02-05|1995-03-24|Roussel Uclaf|New process for the preparation of 6 alpa, 9 alpha-difluorinated steroids and new intermediates.|
    IT1319663B1|2000-11-17|2003-10-23|Farmabios Srl|PROCESS FOR THE PREPARATION OF FLUORO-STEROIDS.|
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    ES2184628B1|2001-07-26|2005-02-01|Ragactives, S.L.|STEREOSELECTIVE PROCEDURE FOR THE PRODUCTION OF INTERMEDIATE 6ALFA-FLUORPREGNANOS.|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/900,886|US4188322A|1978-04-28|1978-04-28|Process for the preparation of 6-halo-pregnanes|
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