1-chloro-4-(isocyanatomethyl)benzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin4(3H)-one 2,2-dioxide (Preparation 52, 1.00 g) and triethylamine (0.60 mL) in DMSO (25 mL) is added a solution of 4-chlorobenzylisocyanate (0.72 g) inDMSO (5 mL) at ambient temperature. After 4 h, 10% HCl (100 mL) is added to the reaction vessel and the aqueous layer is extracted with EtOAc (3×100 mL). The organic layers are combined, dried over MgSO4, filtered, and concentrated in vacuo to afford 0.42g (28%) of the title compound as a lime green solid. Physical characteristics: m.p. 148-149° C.; 1H NMR (300 MHz, CDCl3) δ 15.81, 8.22, 7.93, 7.71, 7.33, 7.16, 4.91, 4.60, 4.52, 3.91, 3.60, 3.48, 1.86, 1.62; IR (diffuse reflectance) 3373, 2940, 1616, 1574, 1543, 1493, 1390, 1327, 1297, 1279, 1253, 1116, 1097, 1077, 1037 cm−1; MS (FAB) m/z 517 (MH+); HRMS (EI) m/z 516.1140 (C25H25ClN2O6S). Anal. Found: C, 57.55; H, 4.95; N, 5.63. the aqueous layer is extracted with EtOAc (3×100 mL) dried over MgSO4 filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (Preparation 35, 0.64 g) and triethylamine (0.27 g) in DMSO (15mL) at ambient temperature is added 4-chloro-benzylisocyanate (0.45 g). The resulting red solution is stirred overnight at ambient temperature and diluted with 10% aqueous HCl (20 mL). The aqueous layer is extracted with EtOAc (3×25 ml). The combined organic layers are dried over MgSO4 and concentrated in vacuo. The residue is dissolved in EtOAc (15 mL) and allowed to stand at ambient temperature overnight. The resulting solid is collected by filtration, washed with EtOAc (10 ml) and dried in vacuo at 50° C. to afford 0.29 g (31%) of the title compound as a tan solid. Physical characteristics: 1H NMR (CDCl3) δ 1.58-1.82, 3.49, 3.60, 3.89, 4.50, 4.56, 4.86, 7.30, 7.42, 7.71, 15.62; IR (diffuse reflectance) 3353, 2945, 1615, 1581, 1541, 1493, 1431, 1366, 1345, 1308, 1296, 1276, 1183, 1119, 1031 cm−1; MS (EI) m/z 522 (M+). Anal. Found: C, 53.17; H, 4.49; N, 5.67. The aqueous layer is extracted with EtOAc (3×25 ml) The combined organic layers are dried over MgSO4 concentrated in vacuo The residue is dissolved in EtOAc (15 mL) to stand at ambient temperature overnight The resulting solid is collected by filtration washed with EtOAc (10 ml) dried in vacuo at 50° C.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide (Preparation 52, 1.00 g) and triethylamine (0.60 mL) in DMSO (25 mL) is added a solution of 4-chlorobenzylisocyanate (0.72 g) in DMSO (5 mL) at ambient temperature. After 4 h, 10% HCl (100 mL) is added to the reaction vessel and the aqueous layer is extracted with EtOAc (3×100 mL). The organic layers are combined, dried over MgSO4, filtered, and concentrated in vacuo to afford 0.42 g (28%) of the title compound as a lime green solid. Physical characteristics: m.p. 148-149° C.; 1H NMR (300 MHz, CDCl3) δ15.81, 8.22, 7.93, 7.71, 7.33, 7.16, 4.91, 4.60, 4.52, 3.91, 3.60, 3.48, 1.86, 1.62; IR (diffuse reflectance) 3373, 2940, 1616, 1574, 1543, 1493, 1390, 1327, 1297, 1279, 1253, 1116, 1097, 1077, 1037 cm−1; MS (FAB) m/z 517 (MH+); HRMS (EI) m/z 516.1140 (C25H25ClN2O6S). Anal. Found: C, 57.55; H, 4.95; N, 5.63. the aqueous layer is extracted with EtOAc (3×100 mL) dried over MgSO4 filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide (Preparation 35, 0.64 g) and triethylamine (0.27 g) in DMSO (15 mL) at ambient temperature is added 4-chloro-benzylisocyanate (0.45 g). The resulting red solution is stirred overnight at ambient temperature and diluted with 10% aqueous HCl (20 mL). The aqueous layer is extracted with EtOAc (3×25 ml). The combined organic layers are dried over MgSO4 and concentrated in vacuo. The residue is dissolved in EtOAc (15 mL) and allowed to stand at ambient temperature overnight. The resulting solid is collected by filtration, washed with EtOAc (10 ml) and dried in vacuo at 50° C. to afford 0.29 g (31%) of the title compound as a tan solid. Physical characteristics: 1H NMR (CDCl3) δ1.58-1.82, 3.49, 3.60, 3.89, 4.50, 4.56, 4.86, 7.30, 7.42, 7.71, 15.62; IR (diffuse reflectance) 3353, 2945, 1615, 1581, 1541, 1493, 1431, 1366, 1345, 1308, 1296, 1276, 1183, 1119, 1031 cm−1; MS (EI) m/z 522 (M+). Anal. Found: C, 53.17; H, 4.49; N, 5.67. The aqueous layer is extracted with EtOAc (3×25 ml) The combined organic layers are dried over MgSO4 concentrated in vacuo The residue is dissolved in EtOAc (15 mL) to stand at ambient temperature overnight The resulting solid is collected by filtration washed with EtOAc (10 ml) dried in vacuo at 50° C.