http://rdf.ncbi.nlm.nih.gov/pubchem/patent/JP-2018520196-A
Outgoing Links
| Predicate | Object |
|---|---|
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D495-04 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D495-04 |
| filingDate | 2016-07-12-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2018-07-26-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | JP-2018520196-A |
| titleOfInvention | Asymmetric preparation of thieno-indole derivatives |
| abstract | The present invention is a novel process for the preparation of thieno-indole derivatives of formula (Ia) or (Ib) comprising the key intermediate (8S) or (8R) 8- (halomethyl) -1-alkyl-7 , 8-dihydro-6H-thieno [3,2-e] indol-4-ol. This invention relates to a process utilizing asymmetric synthesis for the preparation of and a useful intermediate compound of such process. Thieno-indole derivatives are described and claimed in GB 2344818, WO 2013/149948 and WO 2013/149946, which also disclose a method for their preparation. Enantiopure thieno-indole derivatives can now be conveniently prepared by a novel asymmetric synthesis of the key intermediate 8- (halomethyl) -7,8-dihydro-6H-thieno [3,2-e] indole, which Provides a benefit in that the chiral resolution step is avoided and the time and cost of the entire process for this preparation is reduced. The synthesis starts with N-alkylation of 5-amino-4-halo-3-alkyl-1-benzothiophen-7-ol derivatives with enantiopure glycidyl 3-nosylate and then using alkyl Grignard reagents Intramolecular 6-endo-tet cyclization; activation of secondary alcohol Mitsunobu promotes internal spirocyclization to produce 4,4a, 5,6-tetrahydro-8H-cyclopropa [c] thieno [ 3,2-e] indole-8-one derivatives; finally, enantiopure key intermediate 8- (halomethyl) -1-alkyl-7,8- by stereoelectronically controlled regioselective cyclopropane cleavage Dihydro-6H-thieno [3,2-e] indol-4-ol was obtained, which was obtained as WO2013 / 149948 or WO2013 / 1. More derivatized in accordance with the disclosed teachings 9946, the final thieno of formula (Ia) or (Ib) - indole derivatives can be prepared. Such compounds are alkylating compounds with cytotoxic activity and are therefore intact, conjugated to various cancer treatments and cell proliferative disorders, or conjugated with various types of nucleophiles, antibody drug conjugate forms Disclosed are useful in the preparation of derivatives. |
| priorityDate | 2015-07-21-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 131.