2-(2,4-dichlorophenoxy)acetyl 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:; See reaction.notes.procedure_details.

Procedure: A solution of 7.2 g of 2,4-dichlorophenoxyacetyl chloride in 20 ml of tetrahydrofuran was added dropwise to a solution of 2.5 g of 1-methylimidazole in 80 ml of tetrahydrofuran at 0.5°. The resulting slurry was stirred for 30 minutes at 5°, then 4.8 g of 5B was added all at once. The mixture was stirred overnight. Then 0.5 equivalent mole of the imidazole complex in 50 ml of tetrahydrofuran was prepared and added at 5°. The stirred mixture was allowed to rise slowly to room temperature, and stirred overnight. The solvent was stripped; the residue was treated with 1:1 volume mixture of water and methylene chloride. The phases were separated, the water phase was extracted with methylene chloride, the methylene chloride solutions were combined, washed with water and saturated salt solution, dried (MgSO4) and the solvent was stripped to give an oil. The oil was passed through Florisil to give a mush, which was triturated with pentane to give 3-(2,4-dichlorophenoxy)- 1-nitro-1-(tetrahydro-2H-1,3-thiazin-2-ylidene)-2-propanone (5C), as a pale yellow solid, m.p.: 164°-164.5°. The mixture was stirred overnight added at 5° to rise slowly to room temperature stirred overnight The phases were separated the water phase was extracted with methylene chloride washed with water and saturated salt solution dried (MgSO4) to give an oil to give a mush, which was triturated with pentane

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

Procedure: 2,4-Dichlorophenoxyacetic acid (42 mg, 0.190 mmol) was made into acid chloride in a conventional manner. By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (30 mg, 0.095 mmol) obtained in Example 1, (3), and 2,4-dichlorophenoxyacetic acid chloride mentioned above, the title compound (11 mg, yield 22%) was obtained in the same manner as that of Example 1.

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

Procedure: 11 g of 2,4-dichlorophenoxy-acetic acid chloride in solution in 40 ml of methylene chloride were added without exceeding 25° C. to a mixture of 8.6 g of N-(tert-butoxycarbonyl)-1,4-diamino-butane, 120 ml of methylene chloride and 7 ml of triethylamine and the mixture was stirred for 30 minutes, then concentrated to dryness under reduced pressure. The residue was taken up in 200 ml of tetrahydrofuran and the insoluble part was filtered off. The filtrate was evaporated to dryness under reduced pressure to obtain 18.53 g of crude product melting at 107° C. which was crystallized from 740 ml of isopropyl ether to obtain 17.43 g of the expected product melting at 110° C. 5.39 g were chromatographed on silica (eluant: hexane-ethyl acetate (6-4)) to obtain 4.48 g of the sought product melting at 114° C. concentrated to dryness under reduced pressure the insoluble part was filtered off The filtrate was evaporated to dryness under reduced pressure to obtain 18.53 g of crude product melting at 107° C. which was crystallized from 740 ml of isopropyl ether

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

Procedure: 11 g of 2,4-dichlorophenoxy-acetic acid chloride in solution in 40 ml of methylene chloride were added without exceeding 25° C. to a mixture of 8.6 g of N-(tert-butoxycarbonyl)-1,4-diamino-butane, 120 ml of methylene chloride and 7 ml of triethylamine and the mixture was stirred for 30 minutes, then concentrated to dryness under reduced pressure. The residue was taken up in 200 ml of tetrahydrofuran and the insoluble part was filtered off. The filtrate was evaporated to dryness under reduced pressure to obtain 18.53 g of crude product melting at 107° C. which was crystallized from 740 ml of isopropyl ether to obtain 17.43 g of the expected product melting at 110° C. 5.39 g were chromatographed on silica (eluant: hexane-ethyl acetate (6-4)) to obtain 4.48 g of the sought product melting at 114° C. concentrated to dryness under reduced pressure the insoluble part was filtered off The filtrate was evaporated to dryness under reduced pressure to obtain 18.53 g of crude product melting at 107° C. which was crystallized from 740 ml of isopropyl ether

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

Procedure: 46 ml of thionyl chloride were added over 30 minutes to a solution of 130 g of 2,4-dichlorophenoxy-acetic acid in 150 ml of benzene, and the mixture was refluxed for one hour. The solvent and the excess thionyl chloride were eliminated under reduced pressure and the residue was distilled under 0.1 mm of mercury to obtain 91.4 g of the sought product with a boiling point of 120° C. at 0.1 mm of mercury. the mixture was refluxed for one hour the residue was distilled under 0.1 mm of mercury

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

Procedure: 2.3 g of sodium hydride was slurried in 75 ml of dimethylformamide at 5°. To that slurry, at 5°, was added 19.5 g of 1B over a 30-minute period. The stirred mixture was allowed to warm to room temperature and stirred at that temperature for one hour. The mixture then was cooled to 5° and there was added thereto a solution of 25.5 g of 2,4-dichlorophenoxyacetyl chloride in 25 ml of dimethylformamide, over a 20-minute period, the stirred mixture being held at 5°-12°. The stirred mixture was allowed to warm to room temperature and stirred at that temperature overnight. The mixture then was poured into ice water. The solid was filtered, washed with water and dried by air aspiration and ether washing to give a tan-colored solid, which on recrystallization from acetonitrile gave 1, as an off-white solid, m.p.; 191°-192° (with decomposition). The mixture then was cooled to 5° there was added being held at 5°-12° to warm to room temperature stirred at that temperature overnight The solid was filtered washed with water dried by air aspiration and ether washing to give a tan-colored solid, which on recrystallization from acetonitrile gave 1

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

Procedure: A solution of 70 mg (0.290 mmol) of (2,4-dichloro-phenoxy)-acetylchloride in 0.5 mL dichloromethane was added to a solution of 66 mg (0.278 mmol) of 4-(2-diethylamino-ethoxy)-3-methoxy-phenylamine (intermediate product Z6b) and 96 μL (0.56 mmol) of ethyl-diisopropylamine in 1.5 mL abs. dichloromethane and the mixture was stirred for 15 hours at RT. The reaction mixture was evaporated down i. vac. and the residue was purified by column chromatography (silica gel, dichloromethane/MeOH 9:1). The reaction mixture was evaporated down i and the residue was purified by column chromatography (silica gel, dichloromethane/MeOH 9:1)

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

Procedure: 2.2 ml (0.0275 mol) of anhydrous pyridine and 6.7 g (0.027 mol) of 96.3 percent strength 2,4-dichlorophenoxyacetyl chloride are added successively to 8 g (0.027 mol) of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole (cf. U.S. Pat. No. 4,614,533, supra, in 60 ml of dichloromethane with stirring at 0° C. to 5° C. and the mixture is stirred for 16 hours at room temperature. The mixture is worked up by adding 100 ml of dichloromethane, washing successively with dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution, drying the organic phase over magnesium sulphate and removing the solvent in vacuo. 12.7 g (94.3% of theory) of 5-(2,4-dichlorophenoxyacetamido)-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole of melting point 167° C.-180° C. are obtained. washing successively with dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution drying the organic phase over magnesium sulphate removing the solvent in vacuo

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

Procedure: A solution of 7.2 g of 2,4-dichlorophenoxyacetyl chloride in 20 ml of tetrahydrofuran was added dropwise to a solution of 2.5 g of 1-methylimidazole in 80 ml of tetrahydrofuran at 0.5°. The resulting slurry was stirred for 30 minutes at 5°, then 4.8 g of 5B was added all at once. The mixture was stirred overnight. Then 0.5 equivalent mole of the imidazole complex in 50 ml of tetrahydrofuran was prepared and added at 5°. The stirred mixture was allowed to rise slowly to room temperature, and stirred overnight. The solvent was stripped; the residue was treated with 1:1 volume mixture of water and methylene chloride. The phases were separated, the water phase was extracted with methylene chloride, the methylene chloride solutions were combined, washed with water and saturated salt solution, dried (MgSO4) and the solvent was stripped to give an oil. The oil was passed through Florisil to give a mush, which was triturated with pentane to give 3-(2,4-dichlorophenoxy)- 1-nitro-1-(tetrahydro-2H-1,3-thiazin-2-ylidene)-2-propanone (5C), as a pale yellow solid, m.p.: 164°-164.5°. The mixture was stirred overnight added at 5° to rise slowly to room temperature stirred overnight The phases were separated the water phase was extracted with methylene chloride washed with water and saturated salt solution dried (MgSO4) to give an oil to give a mush, which was triturated with pentane