Thieno thiazin-4-one

The last one (6.2 g, 18.4 mmol) was converted into 3,4-dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide 1,1-dioxide (4.87 g, 77%) m.p. 187°C by using the reaction with n-butyl lithium in anhydrous THF at -40°C for 40 min, and then bubbling sulfur dioxide gas for 20 min after which time the mixture was warmed to room temperature. After 30 min at room temperature the mixture was concentrated the residue was dissolved in water, cooled (0°C), sodium acetate trihydrate was added followed by hydroxylamine-O-sulfonic acid. The reaction mixture was stirred at room temperature for 18 h after which time was basified with solid sodium bicarbonate and extracted with ethyl acetate. 

E)-6-chloro-3-[hydroxy(pyridine-2-ylamino)methylene]-2-methyl-2,3-dihydro-4H-thieno [2,3-e] [1,2] thiazin-4-one, 1,1 -dioxide. 

The preparation of two of the three possible isomeric thieno-1,2-thiazin-4-ones (Schemes 5 and 6)128 involved reactions reported12 for the corresponding benzothiazines (see Scheme 1 ). Thus, methyl 3-chlorosul-fonylthiophene-2-carboxylate (152) with sarcosine ethyl ester gave thiophene sulfonamide (153) which, with methanolic sodium methoxide, yielded 3-methoxycarbonyl-4-hydroxy-2-methyl-2H-thieno[2,3-c]-l,2-thiazine 1,1-dioxide (154). Heating 154 with 2-aminothiazole gave 155, a thieno-1,2-thiazine analog of sudoxicam (20) (Scheme 5). 

Pfister and co-workers129 recently prepared derivatives of the third possible thieno-l,2-thiazin-4-one. Methyl 2-chlorosulfonylthiophene-3-car-boxylate (161) with glycine methyl ester gave intermediate 162, which afforded 4- hydroxy- 3- methoxycarbonyl - 2 H - thieno [3,2-e] -1,2- thiazine 1,1 -dioxide (163) upon heating with base. Alkylation of 163 with methyl iodide/sodium hydride gave 164 which afforded a thieno-1,2-thiazine analog (165) of piroxicam (29) when heated with 2-aminopyridine (Scheme 6). 

Pfister and co-workers130 have also prepared the three isomeric thieno-l,2-thiazin-3-one ring systems. The acid chloride 171 of 3-(2-N-methylsulfamoyl)thiopheneacetic acid (170) with sodium bicarbonate gave 3,4-dihydro-2-methyl-3-oxo-2//-thieno[3,2-e]-l,2-thiazine 1,1-dioxide (172) (Eq. 37). 

A number of reports detailing the preparation of novel fused thiophenes have appeared including tetrahydrobenzothieno[2,3- /]imidazole 226 , dihydrothieno[3,2-g]indazole 227 and dihydrothieno[3,2-AJquinazoline 228 , benzothieno[2,3-Z7]pyridine 229 , thieno[2,3-f ]thiadiazine 230 , thieno[5,6-fc]thiazin-4-one 231 , tetrahydrothieno[3,4-c]pyrid-4-one 232 , and dihydrothieno[4,3,2- /][1.4]benzoxazepine 233 . 

Pfister and co-workers recently prepared derivatives of the third possible thieno-l,2-thiazin-4-one. Methyl 2-chlorosulfonylthiophene-3-car-boxylate (161) with glycine methyl ester gave intermediate 162, which afforded... 

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