超声探头大小区别:替诺昔康 [CAS:59804-37-4]合成路线图解??有机化学网

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Chemical Name： 4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide 1,1-dioxide Generic Name： 替诺昔康;Tenoxicam Other Names： Tenoxicam;Ro-120068;Liman;Tilcotil CAS： 59804-37-4 Formula： C₁₃H₁₁N₃O₄S₂ Mole Weight： 337.37832 structure： Company： Kali-Chemie (Originator), Roche (Originator) Usage： Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Non-Steroidal Antiinflammatory Drugs Route 1 The reaction of methyl 3-hydroxythiophene-2-carboxylate (I) with PCl5 in refluxing CCl4 gives 3-chlorothiophene-2-carboxylic acid (II), which by treatment with NaHSO3 and Cu in basic water at 143 C in a pressure vessel is converted into 3-sulfothiophene-2-carboxylic acid (III). The esterification of (III) with refluxing methanol affords methyl 3-sulfothiophene-2-carboxylate (IV), which by reaction with refluxing SOCl2 yields methyl-3-chlorosulfonylthiophene-2-carboxylate (V). The condensation of (V) with sarcosine ethyl ester (VI) in hot CHCl3 gives methyl-3-(N-ethoxycarbonyl-methyl-N-methylsulfamoyl)thiophene-2-carboxylate (VII), which is cyclized by treatment with sodium methoxide in refluxing methanol affording 3-ethoxycarbonyl-4-hydroxy-2-methyl-2H-thieno-[2,3-e]-1,2-thiazine-1,1-dioxide (VIII). Finally, this compound is condensed with 2-aminopyridine (IX) in refluxing toluene.   Intermediates: Serial No. 3-chloro-N-(2-methoxy-4,6-dimethylphenyl)propanamide (IX) 3,3-diethoxypropylamine; 3,3-diethoxy-1-propanamine (V) (I) (II) (III) (IV) (VI) 1-(4-methoxyphenyl)-1-ethanone (VII) 2-bromo-1-(4-methoxyphenyl)-1-ethanone (VIII) Reference 1:     Horomatka, O.; Binder, D.; Pfister, R.; Zeller, P. (F. Hoffmann-La Roche AG); Thienothaiazine derivatives. DE 2537070; FR 2303803; JP 51048694; NL 7510057 . Reference 2:     Serradell, M.N.; Blancafort, P.; Castaner, J.; Tenoxicam. Drugs Fut 1982, 7, 7, 493.