2-methoxyethanesulfonyl chloride

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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1.0 L round bottom flask equipped with mechanical stirrer, addition funnel, thermometer and nitrogen inlet tube was placed 100 grams (0.67 Mol) of 5-amino-2-methylbenzoxazole and 350 mL of pyridine. The slurry was stirred in an ice/ethanol bath at 0° C. then 110 grams (0.69 Mol) of Intermediate 1 was added dropwise so as to maintain a reaction temperature below 7° C. The reaction was stirred at 0° C. for two hours then the resulting red colored mixture was poured into 1.0 L of ethyl acetate. The slurry was stirred for 30 minutes then filtered and the collected solids were discarded. The filtrate was extracted with 4×200 mL of 10% hydrochloric acid and the organic phase was collected and dried over magnesium sulfate. The solvents were removed in vacuo to afford 140 grams (0.52 Mol, 76.7% yield) of desired product as a tan solid. Into a 1.0 L round bottom flask equipped with mechanical stirrer, addition funnel thermometer and nitrogen inlet tube was placed to maintain a reaction temperature below 7° C The reaction was stirred at 0° C. for two hours The slurry was stirred for 30 minutes then filtered The filtrate was extracted with 4×200 mL of 10% hydrochloric acid the organic phase was collected dried over magnesium sulfate The solvents were removed in vacuo

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

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

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (250 mg, 1.05 mmol) was treated with 2-methoxyethanesulfonyl chloride (326 mg, 2.06 mmol) and 1 ml pyridine as a solvent according to the method described in Preparation 15b but stirring at 45° C. during 3 h. The residue was purified using SP1® Purification System (0% to 100% hexane-ethyl acetate) to obtain 80 mg (17% yield, 81% purity) of the title compound. The residue was purified SP1® Purification System (0% to 100% hexane-ethyl acetate)

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (250 mg, 1.05 mmol) was treated with 2-methoxyethanesulfonyl chloride (326 mg, 2.06 mmol) and 1 ml pyridine as a solvent according to the method described in Preparation 15b but stirring at 45° C. during 3 h. The residue was purified using SP1® Purification System (0% to 100% hexane-ethyl acetate) to obtain 80 mg (17% yield, 81% purity) of the title compound. The residue was purified SP1® Purification System (0% to 100% hexane-ethyl acetate)

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

Procedure: To 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) in dichloromethane (4 ml) were added 123 mg (0.77 mmol) 2-methoxyethanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine. The mixture was stirred at room temperature for 12 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with brine. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (4 ml), and to the solution were added 0.175 ml (2.27 mmol) trifluoroacetic acid. The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (acetonitrile/water gradient) to give 32 mg (30% of th.) of the title compound. concentrated under reduced pressure The residue was dissolved in ethyl acetate washed with brine The aqueous layer was re-extracted with ethyl acetate the combined organic layers were washed with brine dried over sodium sulfate filtered concentrated under reduced pressure The residue was dissolved in dichloromethane (4 ml) The mixture was stirred at room temperature for 2 h concentrated under reduced pressure The residue was dissolved in ethyl acetate washed with saturated aqueous sodium bicarbonate solution The organic layer was separated dried over sodium sulfate filtered concentrated under reduced pressure The residue was purified by preparative RP-HPLC (acetonitrile/water gradient)

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

Procedure: (5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride (380 mg, 1 mM) was treated with 2-methoxyethylsulfonyl chloride essentially as in Example 79. Chromatography gave the desired product (65 mg).

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

Procedure: (5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride (380 mg, 1 mM) was treated with 2-methoxyethylsulfonyl chloride essentially as in Example 79. Chromatography gave the desired product (65 mg).

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

Procedure: To a solution of 3-(3-hexyl-6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenylamine (Preparation 12, 0.11 g, 0.40 mmol) in dichloromethane (1.5 ml) was added pyridine (64 mg) in dichloromethane (0.75 ml) and 2-methoxy-1-ethanesulfonyl chloride (J. F. King, J. Y. L. Lam, S. Kronieczny, J. Am. Chem. Soc., 1992, 114 (5), 1743; 0.96 g, 0.60 mmol). The reaction mixture was stirred at room temperature for 16 h and then concentrated in vacuo. The crude residue was purified by chromatography on silica gel eluting with ethyl acetate: 2M ammonia in methanol (99:1). concentrated in vacuo The crude residue was purified by chromatography on silica gel eluting with ethyl acetate