http://rdf.ncbi.nlm.nih.gov/pubchem/patent/ES-2610596-T3
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_19229fe7f5fcc0a484adc464fc5bdb8d |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07B2200-07 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D471-14 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D471-14 |
| filingDate | 2009-03-05-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| grantDate | 2017-04-28-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a0df8b51c33d01a1a278aad5c0b14578 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_c07f8863ceea3e9e114a1256d001cb12 |
| publicationDate | 2017-04-28-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | ES-2610596-T3 |
| titleOfInvention | Procedure for preparing enantiomerically pure indolopyridines |
| abstract | Process for the preparation of compounds of formula I ** Formula ** in which R1 is C2-7 alkyl substituted with -N (R111) R112, in which R111 is C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, hydroxy-C2-4 alkyl, C1-4 alkoxy-C2-4 alkyl, 1N- (C1-4 alkyl) -pyrazolyl, 1N- (H) -pyrazolyl, isoxazolyl, or C1-4 alkyl completely or partially substituted with fluorine, R112 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, or C3-7 cycloalkyl C1-4, or R111 and R112 together and with the inclusion of the nitrogen atom, to which they are attached, form a Het ring, in which Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl , S-oxo-thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4-yl, pyrrolidin-4-20 yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin- 1-yl, 4N- (R113) -homopiperazin-1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl or, triazol-1-yl, or tetrazol-1-yl, wherein R113 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, C1-4 alkyl- carbonyl, amidino, or C1-4 alkyl completely or partially substituted with fluorine, wherein said Het may be optionally substituted with one or two substituents independently selected from fluorine and C1-4 alkyl, R2 is hydrogen, C1 alkyl -4, halogen, trifluoromethyl, C1-4 alkoxy or hydroxyl, R3 is hydrogen, C1-4 alkyl, halogen, trifluoromethyl or C1-4 alkoxy, R4 is C1-4 alkyl, C3-7 cycloalkyl or cycloalkyl C3-7-C1-4 alkyl, R5 is C1-4 alkyl, halogen, C1-4 alkoxy, trifluoromethyl, cyano, hydroxyl, C1-4 phenyl-alkoxy, C1-4 alkoxy-C2-4 alkoxy , C2-4 hydroxy-alkoxy, C3-7 cycloalkoxy, C3-7 cycloalkyl-C1-4 alkoxy, or C1-4 alkoxy completely or predominantly substituted with fluorine, R6 is hydrogen, C1-4C alkyl or halogen , and the salts of these compounds s, said process comprising the steps of a) providing an enantiomerically pure (stereomerically pure) tryptophan derivative of formula IVa, ** Formula ** in which R is methyl or ethyl, and R4, R5, R6 are as defined above , b) Pictet Spengler's reaction of the compounds of formula IVa with 3-hydroxybenzaldehyde of formula III, ** Formula ** in which R2, R3 are as defined above, to obtain a mixture of compounds of formulas IIa and IIb , wherein R, R2, R3, R4, R5, R6 are as defined above, separate the compounds of formulas IIa and IIb to obtain the compounds of formula IIa, c) protect the compounds of formula IIa in the rest of 3 -hydroxyphenyl with a silylating agent, or by adding an acetyl, trifluoroacetyl, benzyl or trityl group to the hydroxy group to obtain the compounds of formula IIa * ** Formula ** in which R, R2, R3, R4, R5, R6 are as defined above, and Z is a protective group, d) heterocyc clarify the compounds of formula IIa * by means of isocyanate R1-N> = C> = O prepared in situ by adding a reaction mixture of carbonyldiimidazole and an amine R1NH2 in a solvent to obtain the compounds of formula Ia, ** Formula ** wherein R1-R6 and Z are as defined above, or to obtain the compounds of formula I, e) deprotect in the rest of 3-hydroxyphenyl the compounds of formula Ia to obtain the compounds of formula I, f) optionally convert the compounds of formula I in salts, wherein in step d) the solvent is a mixture of acetonitrile / toluene, thus adding the reaction mixture of carbonyldiimidazole and the amine R1NH2 to the compounds of formula IIa * in about 1 to 5 about 4 hours and the reaction temperature is continuously increased from about 55 to about 105 ° C by distilling off the acetonitrile, or, in step d) the solvent is pure toluene, thus adding the The reaction mixture of carbonyldiimidazole and the R1NH2 amine to the compounds of formula IIa * in about 20 hours, preferably in about 8 to about 12 hours, under isothermal conditions at the optimum activation temperature of about 100-105 ° C. |
| priorityDate | 2008-03-05-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 218.