2,6-dichlorobenzenesulfonyl 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:0.00; 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:

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

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

Procedure: 2-Amino-5,7-dimethoxy[1,2,4]triazolo[1,5-a]-pyrimidine (0.75 g, 3.8 mmol) and 2,6-dichlorobenzene-sulfonyl chloride (1.86 g, 7.6 mmol) were mixed in dry acetonitrile (15 mL). To this mixture was added dry pyridine (0.61 mL) and dry DMSO (54 μL, 0.7 mmol). The mixture was allowed to stir at room temperature. After 24 hours, the solvent was removed in vacuo, the residue was partitioned between CH2Cl2 (300 mL) and 2N HCl and the solids were collected by vacuum filtration to give a white solid A. The CH2Cl2 was dried (MgSO4) and removed in vacuo to give a white solid B. Both HPLC and NMR indicated that solid A and B are product. The solids were combined to afford the product as a white powder (1.41 g, 92%). mp 211-213° C. Anal: Cacld for C13H11Cl2N5O4S: C, 38.63; H, 2.74; N, 17.33; S, 7.93; found: C, 38.11; H, 2.68; N, 16.83; S, 7.77. 1H NMR (DMSO-d6): δ 12.4 (bs, 1H); 7.64-7.54 (m, 3H); 6.26 (s, 1H); 4.07 (s, 3H); 3.88 (s, 3H). the solvent was removed in vacuo the residue was partitioned between CH2Cl2 (300 mL) and 2N HCl the solids were collected by vacuum filtration to give a white solid A The CH2Cl2 was dried (MgSO4) removed in vacuo to give a white solid B

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

Procedure: A solution of 19.6 g of 2,6-dichlorobenzenesulfonyl chloride dissolved in 70 ml of methylene chloride was added dropwise over 40 minutes to a mixture of 25 ml of methylene chloride, 15.0 ml of triethylamine, 1.0 g of DMAP, and 16.5 g of O-isopropyl P-ethyl(hydroxymethyl)phosphinate, (Example 22, Method A). The addition caused a mild exotherm and the reaction was allowed to stir at room temperature overnight. The reaction mixture was then washed with two 50 ml portions of water, the phases separated, the organic phase dried with magnesium sulfate, filtered, and concentrated to yield 19.6 g of the desired product as a yellow oil. The crude product was diluted with 10 ml of methylene chloride and flash chromatographed using blends of ethyl acetate and hexanes. Similar fractions were combined and rechromatographed to yield 0.95 g of the desired product. The addition The reaction mixture was then washed with two 50 ml portions of water the phases separated the organic phase dried with magnesium sulfate filtered concentrated

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

Procedure: A solution of 20.6 g of diisopropyl P-(hydroxymethyl)-phosphonate, prepared in Example 17, and 14.7 ml of triethylamine diluted in 35 ml of ether was added dropwise over 60 minutes to a mixture of 23.97 g of 2,6-dichlorobenzenesulfonyl chloride and 140 ml of ether. The addition was mildly exothermic. The reaction was allowed to stir at room temperature overnight and then was diluted with 220 ml of ethyl acetate, the ethyl acetate solution washed with two 80 ml portions of water, dried with magnesium sulfate, filtered, and concentrated to yield 35.1 g of the crude desired product as a yellow oil. The oil was dissolved in 25 ml of methylene chloride and flash chromatographed using ethyl acetate and hexanes. Similar fractions were combined to yield 20.5 g of the desired product as an oil. The addition the ethyl acetate solution washed with two 80 ml portions of water dried with magnesium sulfate filtered concentrated to yield 35.1 g of the crude desired product as a yellow oil flash chromatographed