2-chloro-6-methylbenzenesulfonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 7.20 g of 2-chloro-6-methylbenzenesulfonyl chloride dissolved in 30 ml of THF was added dropwise over 30 minutes to a reaction mixture 5.80 g of di-n-propyl(hydroxymethyl)-phosphine oxide, (Example 23), 30 ml of THF, and 4.04 g of triethylamine. The addition caused a mild exotherm and the reaction was allowed to stir at room temperature over the weekend. Most of the THF was removed and the resulting material was partitioned between 200 ml of ethyl acetate and 70 ml of water, the organic phase rewashed with an additional 70 ml of water, dried with magnesium sulfate, filtered and concentrated to yield 6.5 g of the crude desired product as a dark tan oil. The crude product was diluted with 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of isopropanol and ethyl acetate, similar fractions were combined and concentrated under reduced pressure to yield the partially purified product. This material was dissolved in 150 ml of ethyl acetate, washed with three 50 ml portions of water, dried with magnesium sulfate, filtered and concentrated to yield 2.4 g of the desired product as a white solid: melting point 51°-53° C. The addition Most of the THF was removed the resulting material was partitioned between 200 ml of ethyl acetate and 70 ml of water dried with magnesium sulfate filtered concentrated to yield 6.5 g of the crude desired product as a dark tan oil chromatographed on Merck silica gel (230-400 mesh) concentrated under reduced pressure to yield the partially purified product washed with three 50 ml portions of water dried with magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 21.7 g of 2-chloro-6-methylbenzenesulfonyl chloride dissolved in 40 ml of ether was added dropwise over 90 minutes to a mixture of 20.6 g of diisopropyl P-(hydroxymethyl)-phosphonate, (Example 17), 80 ml of ether, and 15.4 ml of triethylamine. The addition was mildly exothermic and the reaction was cooled using a cool water bath (no ice). The reaction was allowed to stir overnight at room temperature and then was diluted with 300 ml of ethyl acetate, washed with three 100 ml portions of water, the organic phase dried with magnesium sulfate, filtered and concentrated under reduced pressure to yield 34.0 g of the desired product as a yellow oil. The addition the reaction was cooled washed with three 100 ml portions of water the organic phase dried with magnesium sulfate filtered concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.63 g of 2-chloro-6-methylbenzenesulfonyl chloride dissolved in 20 ml of anhydrous ether was added dropwise over a 15 minute period to a mixture of 3.50 g of diethyl P-(hydroxymethyl)phosphonate (Example 17), 5 ml of triethylamine and 15 ml of anhydrous ether. The addition was mildly exothermic and a white precipitate began to form shortly after the addition of the sulfonyl chloride was begun. The reaction was stirred at room temperature overnight. After 48 hours of additional stirring the reaction solution was diluted with 200 ml of ethyl acetate and 80 ml of water. The organic phase was washed with two 90 ml portions of water, dried with magnesium sulfate, filtered and concentrated to yield 6.4 g of an oil which solidified upon standing, mp 41°-43° C. The addition to form shortly After 48 hours of additional stirring the reaction solution The organic phase was washed with two 90 ml portions of water dried with magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to the methods described in reagent preparation 26 using 5-bromo-2-chloropyridin-3-amine and 2-chloro-6-methylbenzene-1-sulfonyl chloride in step 1. MS (EI) for C12H9BrCl2N2O2S: 393, 395, 397 (Br+Cl isotopes, MH+). Prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to the methods described in reagent preparation 26 using 5-bromo-2-chloropyridin-3-amine and 2-chloro-6-methylbenzene-1-sulfonyl chloride in step 1. MS (EI) for C12H9BrCl2N2O2S: 393, 395, 397 (Br+Cl isotopes, MH+). Prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The intermediate from example 146 step 7 was treated with 2-chloro-6-methyl-benzenesulfonyl chloride according to the procedure in Example 87 step 2 to generate the desired product in 96% yield.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The intermediate from example 142 step 12 was treated with 2-chloro-6-methyl-benzenesulfonyl chloride according to the procedure in Example 87 step 2 to generate the desired product in 85% yield.