http://rdf.ncbi.nlm.nih.gov/pubchem/patent/ES-307301-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_6b6fc801b5bfe5304ffa40d938db6e09 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D211-70 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D211-82 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D221-26 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D213-30 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D221-26 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D211-82 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D211-70 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D213-30 |
| filingDate | 1964-12-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1965-05-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | ES-307301-A1 |
| titleOfInvention | PROCEDURE FOR THE PREPARATION OF NEW 6, 7-SUBSTITUTED BENZOMORPHANS |
| abstract | The invention comprises compounds of formula <FORM:1077711/C2/1> wherein X is oxygen or sulphur, R1 is hydrogen, hydroxy or C1- 6 alkoxy or alkanoyloxy, R2 is C1- 6 alkyl, b -methoxyethyl or phenyl optionally substituted by a halogen atom or a hydroxy or C1- 9 alkoxy group, R3 is hydrogen or a C1- 3 alkyl group, R4 is hydrogen, or a C1- 5 alkyl, C2- 5 alkenyl, phenyl, chlorophenyl, bromophenyl or C7- 8 phenyl-alkyl group, R5 is hydrogen or a C1- 6 alkyl group, or the group -NR4R5 forms a saturated heterocycle having up to 7 carbon atoms in which the nitrogen atom is the only hetero-atom or a morpholino group, acid addition salts thereof, and their preparation by (a) reaction of an N-unsubstituted benzomorphan, in the presence of an acid-binding agent, with phosgene and an amine HNR4R5 or with a compound HalCONR4R5, or with an isocyanate of formula R4-N=C=X or (VII) M\sJ \sKN=C=O wherein M is an alkali metal, (b) reaction of an N-cyano-benzomorphan with water or hydrogen sulphide, the former optionally under oxidative conditions, (c) reaction of an N-unsubstituted or N-alkyl-benzomorphan with a compound of formula Hal-COOR6, wherein R6 is a C1- 6 alkyl group, to form an N-alkoxycarbonyl-benzomorphan and treating this with an alkali metal amide, (d) O-alkylation, O-acylation or ether or ester hydrolysis, (e) conversion of a carbamyl group to a thiocarbamyl group, or (f) optical resolution by formation of optically active salts, followed by regeneration of the base. N - Cyano - benzomorphan starting materials are prepared by cyclization of a compound of formula <FORM:1077711/C2/2> in the presence of a Lewis acid to form an N-methyl-benzomorphan which may be optically resolved by formation of an optically active salt, followed by regeneration of the base, acylating any free hydroxy groups, and reacting the product with cyanogen bromide. 21 - Methoxy - 5 - phenyl - 6,7 - benzomorphan hydrochloride is prepared by treatment of 21-hydroxy - 5 - phenyl - 6,7 - benzomorphan with ethereal diazomethane, followed by hydrochloric acid. 1 - Methyl - 2 - (p - methoxybenzyl) - 4 - (p-chlorophenyl) - 1,2,5,6 - tetrahydropyridine hydrobromide is prepared by reaction of 4-(p-chlorophenyl) - 1,2,5,6 - tetrahydropyridine with formaldehyde and formic acid to form the N-methyl derivative, treatment of this with p-methoxybenzyl chloride to form the N-methyl - N - (p - methoxybenzyl) compound, and treating this with phenyl lithium and hydrogen bromide. 1 - Methyl - 1 - (p - methoxybenzyl) - 4 - (p-hydroxyphenyl) - 1,2,5,6 - tetrahydropyridine hydrobromide is prepared by reaction of 1-methyl-4-piperidone with phenol and hydrogen chloride to form 1-methyl-4-(p-hydroxyphenyl)-1,2,5,6 -tetrahydropyridine, reacting this with p-methoxybenzyl chloride to form the N-methyl-N-(p-methoxybenzyl)-compound, and treating this with potassium amide in liquid ammonia. The compounds of the invention have analgesic, anti-tussive and morphine-antagonistic activity and may be used in pharmaceutical compositions in combination with a carrier, for example in forms suitable for oral or parenteral administration. |
| priorityDate | 1963-12-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 70.