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Isaglitazone, Netoglitazone, RWJ-241947, MCC-555

萘格列酮Chemical Name: 5-[6-(2-Fluorobenzyloxy)naphthalen-2-ylmethyl]thiazolidine-2,4-dione
CAS No. 161600-01-7, 161599-99-1 (sodium salt)
项目整合开发状态: Phase II
项目研究机构: Mitsubishi Pharma (Originator), Johnson & Johnson (Licensee)
合成路线:Reaction of aldehyde (III) with 2-fluorobenzyl alcohol (VIII) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF furnishes 6-(2-fluorobenzyloxy)naphthalene-2-carbaldehyde (IX) ,which is then reduced with NaBH4 in ethanol/THF to give the naphthalenemethanol derivative (X).Halogenation of (X) by means of iodide,triphenylphosphine and imidazole in THF yields the naphthylmethyl iodide derivative (XI),which is finally condensed with thiazolidine-2,4-dione (IV) by means of HMPA and butyl lithium in THF.
📌 参考资料/链接:
参考文献标题:Naphthalene derivs.
文献作者:Ueno,H.; Oe,T.; Suehiro,I.; Nakamura,F.(Mitsubishi Chemical Corp.)
参考来源:EP 0604983; JP 1994247945; US 5594016

📄 详细内容


合成路线:Reduction of 6-hydroxynaphthalen-2-carboxylic acid (I) by means of trimethyl borate and BH3.THF complex ?obtained by reaction of NaBH4 and dimethyl sulfate in THF ?yields the naphthyl carbinol derivative (II),which is oxidized to aldehyde (III) with either manganese dioxide in DMF or acetone,mixtures of CuCl2,CuBr2 or FeCl3 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in DMF or O2,TEMPO and a ruthenium catalyst in chlorobenzene.Condensation of aldehyde (III) with thiazolidine-2,4-dione (IV) in 2-methoxyethanol,2-propanol,DMF or DMSO gives 5-(6-hydroxynaphthalen-2-ylmethylene)thiazolidine-2,4-dione (V),which is then reduced with either H2 over catalyst or cyclohexene to provide 5-(6-hydroxynaphthalen-2-ylmethyl)thiazolidine-2,4-dione (VI).Finally,compound (VI) is condensed with 2-fluorobenzyl chloride (VII) by means of NaH or KH in DMF,DMSO or NMP.

参考文献标题:Preparation method of naphthalene derivs.
文献作者:Ohe,T.; Suehiro,I.; Sekiya,T.; Ueno,H.(Mitsubishi Chemical Corp.)
参考来源:JP 1998139768


合成路线:Reduction of 6-hydroxynaphthalen-2-carboxylic acid (I) by means of trimethyl borate and BH3.THF complex ?obtained by reaction of NaBH4 and dimethyl sulfate in THF ?yields the naphthyl carbinol derivative (II),which is oxidized to aldehyde (III) with either manganese dioxide in DMF or acetone,mixtures of CuCl2,CuBr2 or FeCl3 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in DMF or O2,TEMPO and a ruthenium catalyst in chlorobenzene.Condensation of aldehyde (III) with thiazolidine-2,4-dione (IV) in 2-methoxyethanol,2-propanol,DMF or DMSO gives 5-(6-hydroxynaphthalen-2-ylmethylene)thiazolidine-2,4-dione (V),which is then reduced with either H2 over catalyst or cyclohexene to provide 5-(6-hydroxynaphthalen-2-ylmethyl)thiazolidine-2,4-dione (VI).Finally,compound (VI) is condensed with 2-fluorobenzyl chloride (VII) by means of NaH or KH in DMF,DMSO or NMP.

参考文献标题:6-Hydroxy-2-naphthylcarbinol and process for the preparation thereof
文献作者:Ichikawa,S.; Iwane,H.; Qu,J.(Mitsubishi Chemical Corp.)
参考来源:WO 0073252


合成路线:Reduction of 6-hydroxynaphthalen-2-carboxylic acid (I) by means of trimethyl borate and BH3.THF complex ?obtained by reaction of NaBH4 and dimethyl sulfate in THF ?yields the naphthyl carbinol derivative (II),which is oxidized to aldehyde (III) with either manganese dioxide in DMF or acetone,mixtures of CuCl2,CuBr2 or FeCl3 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in DMF or O2,TEMPO and a ruthenium catalyst in chlorobenzene.Condensation of aldehyde (III) with thiazolidine-2,4-dione (IV) in 2-methoxyethanol,2-propanol,DMF or DMSO gives 5-(6-hydroxynaphthalen-2-ylmethylene)thiazolidine-2,4-dione (V),which is then reduced with either H2 over catalyst or cyclohexene to provide 5-(6-hydroxynaphthalen-2-ylmethyl)thiazolidine-2,4-dione (VI).Finally,compound (VI) is condensed with 2-fluorobenzyl chloride (VII) by means of NaH or KH in DMF,DMSO or NMP.

合成路线:Reaction of aldehyde (III) with 2-fluorobenzyl alcohol (VIII) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF furnishes 6-(2-fluorobenzyloxy)naphthalene-2-carbaldehyde (IX) ,which is then reduced with NaBH4 in ethanol/THF to give the naphthalenemethanol derivative (X).Halogenation of (X) by means of iodide,triphenylphosphine and imidazole in THF yields the naphthylmethyl iodide derivative (XI),which is finally condensed with thiazolidine-2,4-dione (IV) by means of HMPA and butyl lithium in THF.
参考文献标题:Netoglitazone
文献作者:del Fresno,M.; Sorbera,L.A.; Castar,J.; Silvestre,J.S.
参考来源:Drugs Fut 2002,27(2),132


产品链接: CAS No. 161600-01-7››