http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EA-201070061-A1
Outgoing Links
| Predicate | Object |
|---|---|
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/Y02P20-55 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J21-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J41-0083 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J51-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J41-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J41-0094 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P15-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J21-006 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P15-18 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J51-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J41-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J21-00 |
| filingDate | 2008-06-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2010-04-30-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | EA-201070061-A1 |
| titleOfInvention | INDUSTRIAL METHOD FOR SYNTHESIS OF 17-ACETOXY-11β- [4- (DEMITILAMINO) PHENYL] -21-METHOXI-19-NORPREGN-4,9-DIEN-3,20-DIONA AND KEY INTERMEDIATE CONNECTIONS OF THIS SPOT |
| abstract | The present invention relates to a method for the synthesis of the known 17-acetoxy-11β- [4- (dimethylamino) phenyl] -21-methoxy-19-norpregn-4,9-diene-3,20-dione (hereinafter referred to as CDB-4124) of the formula (I) from 3,3- [1,2-ethanediyl-bis (oxy)] -estr-5 (10), 9 (11) -diene-17-one of the formula (II). Compound CDB-4124 belongs to the group of antihormones. The method of the present invention is as follows: i) double-bonded epoxide formation at position 5 (10) by reaction of 3,3- [1,2-ethanediyl bis (hydroxy)] -estr-5 (10), 9 (11) diene-17-one of formula (II) with hydrogen peroxide; ii) attaching the in situ obtained cyanide to position 17 of the obtained 5,10α-epoxy-3,3- [1,2-ethanediyl bis (hydroxy)] - 5α-oestr-9 (11) -en-17-one of the formula ( III); iii) silylation of the hydroxyl group at position 17 of the resulting 5,10α-epoxy-3,3- [1,2-ethanediyl bis (hydroxy)] - 17α-hydroxy-5α-oestra-9 (11) -en-17p-carbonitrile formula (IV) trimethylchlorosilane; iv) the interaction of the obtained 5,10α-epoxy-3,3- [1,2-ethanediyl-bis (oxy)] - 17- [trimethylsilyloxy] -5α-oestra-9 (11) -en-17β-carbonitrile of the formula (V ) with Grignard reagent 4- (dimethylamino) phenylmagnesium bromide in the presence of CuCl (Toych reaction); v) silylation of the hydroxyl group at position 5 of the obtained 11β- [4- (dimethylamino) phenyl] -3,3- [1,2-ethanediyl-bis (oxy)] - 5-hydroxy-17α- [trimethylsilyl- (oxy)] -5α-oestr-9en-17β-carbonitrile of the formula (VI) with trimethylchlorosilane; vi) the interaction of the obtained 11β- [4- (dimethylamino) phenyl] -3,3- [1,2-ethanediyl bis (hydroxy)] - 5.17α-bis- [trimethylsilyl- (hydroxy)] - 5α-oestra- 9-ene 17β-carbonitrile of the formula (VII) with diisobutylaluminum hydride and the subsequent addition of acid to the reaction mixture; vii) methoxymethylation of the obtained 11β- [4- (dimethylamino) phenyl] -3,3- [1,2-ethanediyl-bis (oxy)] - 5.17α-bis- [trimethylsilyl- (oxy)] - 5α- oestra-9-en-17β-carbaldehyde of the formula (VIII) with Grignard methoxymethyl reagent obtained in situ, with the simultaneous hydrolysis of trimethylsilyl protecting groups; viii) oxidation of the hydroxyl group at position 20 of the obtained 17,20ξ-dihydroxy-11β- [4- (dimethylamino) phenyl] -21-methoxy-19-norpregn-4,9-dien-3-one of the formula (IX) with dicyclohexylcarbodiimide in the presence of dimethyl sulfoxide and a strong organic acid (Shvern oxidation), and in this case subsequent chromatographic purification; ix) acetylation of the hydroxyl group at position 17 of the obtained 11β- [4- (dimethylamino) phenyl] -17-hydroxy-21-methoxy-19-norpregn-4,9-diene-3,20-dione of formula (X) with acetic anhydride in the presence of perchloric acid, and in this case, the obtained 7-acetoxy-11β- [4- (dimethylamino) phenyl)] - 21-methoxy-19-nopregna-4,9-diene-3,20-dione of the formula (I) is purified by chromatography. The present invention also relates to new intermediates of formula (VII) and (VIII). |
| priorityDate | 2007-06-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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