http://rdf.ncbi.nlm.nih.gov/pubchem/patent/ES-2360607-T3
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_1c89ce4d9ac03f9acd8ddede1162f94d |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D209-44 |
| filingDate | 2006-07-07-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| grantDate | 2011-06-07-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_3336487c228aa371b95fac9ecf750e12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_b7e4bd1a878f73a42c73f8c3eef44dc5 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_9174ebc1776b73746b3b509cf64b3126 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_bc2053c67382feaf2a6f4aa7f0afa93b |
| publicationDate | 2011-06-07-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | ES-2360607-T3 |
| titleOfInvention | MANUFACTURING PROCEDURE FOR ANTAGONISTS OF THE HYDROISOINDOLINE TAQUIQUININE RECEPTOR. |
| abstract | A process for making hydroisoindoline tachykinin receptor antagonists of Formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 is selected from the group consisting of (2) C 1-6 alkyl, which is unsubstituted or substituted. with halogen, hydroxyl or phenyl, (3) cyclopentenone, which is unsubstituted or substituted with halogen, hydroxyl or methyl (4) - (CO) -C 1-6 alkyl, (5) - (CO) -NH2, (6) - (CO) -N C1-6 alkyl, and (7) - (CO) -N (C1-6 alkyl) (C1-6 alkyl); X is independently selected from the group consisting of: (1) hydrogen, (2) fluorine, and (3) methyl; comprising: Step (a) reacting a phenylacetic acid of Formula (2) with SOCl2 in an aprotic solvent optionally in the presence of a first catalyst to provide a compound of Formula (3) Step (b) reacting the compound of Formula ( 3) with NHMeOMe in the presence of an aqueous inorganic base to provide a Weinreb amide of Formula (4) Step (c) react the Weinreb amide of Formula 4 with a suitable Grignard reagent in a second aprotic solvent followed by a first inactivation with Ac2O and a second inactivation with an aqueous inorganic acid to provide a dwarf of Formula (5) Step (d) reacting the dwarf of Formula (5) with a silane reagent in a third aprotic solvent and an organic base to provide a diene of Formula (6) Step (e) reacting a diene of Formula (6) with a fumarate of Formula (7) in which R is (-) - methyl and a Lewis acid in a non-Polish solvent r to provide a compound of Formula (8) * Step (f) hydrolyze a compound of Formula (8) with suitable hydrolysis reagents in a polar organic solvent to provide a compound of Formula (9) Step (g) reduce the functionality of ketone of the compound of Formula (9) with a first reducing agent, followed by reduction of CO2R with a second reducing agent in an aprotic solvent to provide a triol of Formula (10) Step (h) reacting the triol of Formula (10) with an alkylsulfonyl chloride in the presence of an organic base to provide a compound of Formula (11) in which R 2 is methyl, ethyl or propyl, Step (i) reacting the compound of Formula (11) with a compound of Formula (12) in the presence of an acid catalyst in an aprotic solvent to produce a compound of Formula (13) Step (j) cycling the compound of Formula (13) with allylamine in a polar solvent to provide a compound of Formula (14) Step (k) reacting the compound of Formula (14) with a third catalyst followed by the addition of acid to provide a compound of Formula (15) optionally in the form of an acid salt; Step (l) reacting the acid salt of the compound of Formula (15) with a functionalization reagent in a polar solvent to provide the compound of Formula (I) |
| priorityDate | 2005-07-11-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 191.