dodecane-1-sulfonyl chloride

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Dodecanesulfonyl chloride (0.38 g, 1.4 mmol) was added to a stirred suspension of 5-(5,6-dichloro-1H-benzoimidazol-2-yl)-2-methoxy-phenylamine from Step B (0.6 g, 1.4 mmol) in pyridine (6 mL) under an inert atmosphere, warmed briefly to 80° C. then stirred at room temperature. After approximately 20 hours the mixture was poured into water (60 mL), stirred, and acidified with aqueous HCl. After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) and the combined extracts were washed with water then 0.5 M sodium bicarbonate solution. A little saturated brine was added to assist with stratification. The organic phase was washed with saturated brine, dried over MgSO4, and stripped of solvent to leave the crude product as a crystalline residue. Recrystallization from acetonitrile followed by chromatography on silicagel in CHCl3/EtOAc (9:1) afforded the product (0.03 g), mp 203-204° C. stirred After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) the combined extracts were washed with water A little saturated brine was added The organic phase was washed with saturated brine dried over MgSO4 to leave the crude product as a crystalline residue Recrystallization from acetonitrile

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Dodecanesulfonyl chloride (0.38 g, 1.4 mmol) was added to a stirred suspension of 5-(5,6-dichloro-1H-benzoimidazol-2-yl)-2-methoxy-phenylamine from Step B (0.6 g, 1.4 mmol) in pyridine (6 mL) under an inert atmosphere, warmed briefly to 80° C. then stirred at room temperature. After approximately 20 hours the mixture was poured into water (60 mL), stirred, and acidified with aqueous HCl. After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) and the combined extracts were washed with water then 0.5 M sodium bicarbonate solution. A little saturated brine was added to assist with stratification. The organic phase was washed with saturated brine, dried over MgSO4, and stripped of solvent to leave the crude product as a crystalline residue. Recrystallization from acetonitrile followed by chromatography on silicagel in CHCl3/EtOAc (9:1) afforded the product (0.03 g), mp 203-204° C. stirred After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) the combined extracts were washed with water A little saturated brine was added The organic phase was washed with saturated brine dried over MgSO4 to leave the crude product as a crystalline residue Recrystallization from acetonitrile

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

Procedure: 1-Dodecanesulfonyl chloride (0.3 g, 1.1 mmol) was added to a stirred solution of 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenyl-amine from Example 3 (0.3 g, 1.11 mmol) in pyridine (3 mL) under an inert atmosphere at room temperature. After approximately 20 hours the mixture was poured into water (30 mL), stirred, and acidified with aqueous HCl. After several hours the precipitate was filtered off, rinsed three times with water, and dried. Recrystallization from ethanol afforded the product (0.25 g), mp 148-149° C. After several hours the precipitate was filtered off rinsed three times with water dried Recrystallization from ethanol

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Dodecanesulfonyl chloride (0.38 g, 1.4 mmol) was added to a stirred suspension of 5-(5,6-dichloro-1H-benzoimidazol-2-yl)-2-methoxy-phenylamine from Step B (0.6 g, 1.4 mmol) in pyridine (6 mL) under an inert atmosphere, warmed briefly to 80° C. then stirred at room temperature. After approximately 20 hours the mixture was poured into water (60 mL), stirred, and acidified with aqueous HCl. After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) and the combined extracts were washed with water then 0.5 M sodium bicarbonate solution. A little saturated brine was added to assist with stratification. The organic phase was washed with saturated brine, dried over MgSO4, and stripped of solvent to leave the crude product as a crystalline residue. Recrystallization from acetonitrile followed by chromatography on silicagel in CHCl3/EtOAc (9:1) afforded the product (0.03 g), mp 203-204° C. stirred After several hours the mixture was extracted with dichloromethane (60 mL, 30 mL) the combined extracts were washed with water A little saturated brine was added The organic phase was washed with saturated brine dried over MgSO4 to leave the crude product as a crystalline residue Recrystallization from acetonitrile

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

Procedure: 1-Dodecanesulfonyl chloride (0.3 g, 1.1 mmol) was added to a stirred solution of 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenyl-amine from Example 3 (0.3 g, 1.11 mmol) in pyridine (3 mL) under an inert atmosphere at room temperature. After approximately 20 hours the mixture was poured into water (30 mL), stirred, and acidified with aqueous HCl. After several hours the precipitate was filtered off, rinsed three times with water, and dried. Recrystallization from ethanol afforded the product (0.25 g), mp 148-149° C. After several hours the precipitate was filtered off rinsed three times with water dried Recrystallization from ethanol

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

Procedure: Pyridine (5 mL) was added to a mixture of 1-dodecane-sulfonyl chloride (Maybridge) (0.8 g, 3.0 mmol) and 3-amino-4-methoxy-N-(3,4-dichloro-phenyl)-benzamide from Example 4 (0.73 g, 3.0 mmol) and stirred at room temperature. After 5 days the mixture was heated on a steambath for 1.5 hours, allowed to cool, and added to water (150 mL), acidified with 4N HCl, and stirred for an hour. The precipitate was filtered off, rinsed with water then with ethanol and dried to afford the product (1.3 g); m.p. 151-152° C. after recrystallization from ethanol and chromatography on silica gel in CHCl3/EtOAc (9:1). After 5 days the mixture was heated on a steambath for 1.5 hours to cool stirred for an hour The precipitate was filtered off rinsed with water with ethanol and dried

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

Procedure: Pyridine (5 mL) was added to a mixture of 1-dodecane-sulfonyl chloride (Maybridge) (0.8 g, 3.0 mmol) and 3-amino-4-methoxy-N-(3,4-dichloro-phenyl)-benzamide from Example 4 (0.73 g, 3.0 mmol) and stirred at room temperature. After 5 days the mixture was heated on a steambath for 1.5 hours, allowed to cool, and added to water (150 mL), acidified with 4N HCl, and stirred for an hour. The precipitate was filtered off, rinsed with water then with ethanol and dried to afford the product (1.3 g); m.p. 15-152° C. after recrystallization from ethanol and chromatography on silica gel in CHCl3/EtOAc (9:1). After 5 days the mixture was heated on a steambath for 1.5 hours to cool stirred for an hour The precipitate was filtered off rinsed with water with ethanol and dried

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.6 g of 2-(nitromethylene)-tetrahydro-2H-1,3-thiazine, 3.18 g of ethyldiisopropylamine and 20 ml of methylene chloride were mixed. The mixture was cooled to and stirred at -60° C. under a nitrogen atmosphere while 2.95 g of dodecanesulfonyl chloride was added in portions over a 10 minute period. The mixture was allowed to warm to 10° C. (2.5 hours), then stirred at 10° C. for 1 hour and at 20° C. for 1.5 hours. The resulting mixture was poured into water, and the organic phase was separated, dried (MgSO4), filtered and stripped of solvent. The residue, a gum, was chromatographed over silica gel, using methylene chloride as eluent. After workup the product was recrystallized from ethanol to give N-(dodecylsulfonyl)-2-(nitromethylene)-tetrahydro-2H-1,3-thiazine (3A) as a solid, m.p.: 116°-117° C. The mixture was cooled to and was added in portions over a 10 minute period the organic phase was separated dried (MgSO4) filtered The residue, a gum, was chromatographed over silica gel was recrystallized from ethanol