Thieno thiazines

CN (4R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-27/-thieno[3,2-e]-l,2-thiazine-6-sulfonamide 1,1-dioxide... 

CN 6-Chloro-4-hydroxy-2-methyl-A-2-pyridinyl-2//-thieno[2,3-e]-l,2-thiazine-3-carboxamide 1,1-dioxide... 

Related thieno[3,2-( ][l,2]thiazines 93 and 94 have been prepared by the pyrolysis of 95 (Equation 6) <2005BMC2052> and the base-promoted methanesulfonate elimination of 96 (Equation 7) <2000BMC957>. 

Chloro-4-hydroxy-2-methyl-1,1 -dioxo-1,2-dihydro-1 l6-thieno[2,3 e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide, 6-chloro-4-hydroxy-2-methyl-/V-(2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carbox-amide-1,1-dioxide, CnH,oC N30AS2, Mr 371.81, mp 225-230 °C (decomp.)... 

A solution of the above product (19.2 g, 0.093 mol) in DMF (125 mL) was added to a suspension of sodium hydride (3.08 g, 80% oil dispersion, 0.103 mol) in DMF at 006. When the addition was completed the ice bath was removed and the reaction 20 mixture stirred at ambient temperature for 1 h. The reaction mixture was cooled to 0°C and 2-bromoethyl methylether (13.6 mL, 0.14 mol) was added. The reaction mixture was stirred at ambient temperature for 18 h after which time it was evaporated to dryness. The residue was suspended in brine (100 mL) and extracted with methylene chloride (4x80 mL). The combined extracts were dried (MgS04), filtered and evaporated to a solid which was recrystallized from ethyl acetate to give the desired subject (17.4 g). Chromatography of the mother liquor (silica, 3% ethanol/methylene chloride) furnished more subject which was combined with the first batch to give a total of 19.3 g (78%) of 3,4-dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide. 

Dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide (4.9 g, 50 18.6 mmol) was converted to the 4-(l-ethoxy)ethoxy-3,4-dihydro-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide (6.2 g, 99%) using the reaction with p-toluensulfonic acid and ethylvinyl ether at 0°C in tetrahydrofuran for 2 hrs. 

Dihydro-2-(2-methoxy)ethyl-4-propylamino-2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide-l,1-dioxide hydrochloride was obtained by the reaction of 3,4-dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide-1,1-dioxide in THF containing triethylamine with tosyl chloride at -16°C and the next stirring for 18 hrs at room temperature. After which time the mixture was cooled to 0°C and propylamine was added, the desired product (0.57 g, 46%) was obtained m.p. 178°-181°C. 

C yHlyClN2 100643-71-8) see Loratadine (4.V)-6-chloro-3,4-dihydro-2//-thieno[3,2-c]-l,2-thiazin-4-ol 1,1-dioxide... 

Table 2 Photo-decomposition of thieno[3,2-c][lA4,2] thiazines (84) and related species <86JCS(P1)497>.

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