2-diethoxyphosphorylacetyl 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:; See reaction.notes.procedure_details.

Procedure: Pyridine (3.7 ml, 45.7 mmol) is added to a solution of 2-amino-4-chloro-benzaldehyde (6.18 g, 39.7 mmol) in 170 ml of anhydrous toluene, followed dropwise by a solution of chlorocarbonylmethylphosphonic acid diethyl ester (9.8 g, 45.7 mmol) in 15 ml of anhydrous toluene whilst maintaining the reaction mixture at a temperature of less than 30° C. When the addition is complete, the mixture is stirred for 1 hour at room temperature. The reaction mixture is washed several times with water and then with a 1N HCl solution, and then again with water. Finally the mixture is washed with an aqueous saturated NaCl solution. The organic phase is dried over MgSO4, and filtration is carried out, followed by evaporation to obtain the expected crude product in the form of an orange oil. The crude product is used in the following step. whilst maintaining the reaction mixture at a temperature of less than 30° C When the addition The reaction mixture is washed several times with water Finally the mixture is washed with an aqueous saturated NaCl solution The organic phase is dried over MgSO4, and filtration followed by evaporation

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

Procedure: 2.0 g (13.51 mmol) of 2-hydroxyethylmethyl oxalate and 1.7 g (16.8 mmol) of triethylamine were dissolved in 50 mL of ethyl acetate, and 3.1 g (14.5 mmol) of diethyl (2-chloro-2-oxoethyl)phosphonate was dropwise added thereto at 15° C. or lower, taking 15 minutes. This was stirred at room temperature for 1 hour, and the disappearance of the starting materials was confirmed through gas chromatography. The reaction liquid was washed with water, the organic layer was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (ethyl acetate for elution) to give 1.8 g (yield 42%) of the intended 2-(2-(diethoxyphosphoryl)acetoxyl)ethyl methyl oxalate. The reaction liquid was washed with water the organic layer was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (ethyl acetate for elution)

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

Procedure: 2.0 g (13.51 mmol) of 2-hydroxyethylmethyl oxalate and 1.7 g (16.8 mmol) of triethylamine were dissolved in 50 mL of ethyl acetate, and 3.1 g (14.5 mmol) of diethyl (2-chloro-2-oxoethyl)phosphonate was dropwise added thereto at 15° C. or lower, taking 15 minutes. This was stirred at room temperature for 1 hour, and the disappearance of the starting materials was confirmed through gas chromatography. The reaction liquid was washed with water, the organic layer was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (ethyl acetate for elution) to give 1.8 g (yield 42%) of the intended 2-(2-(diethoxyphosphoryl)acetoxyl)ethyl methyl oxalate. The reaction liquid was washed with water the organic layer was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (ethyl acetate for elution)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The above 2-(diethoxyphosphoryl)acetic acid chloride and 31.4 g (0.56 mol) of propargyl alcohol were dissolved in 100 mL of toluene and cooled to 5° C. 67.1 g (0.66 mol) of triethylamine was dropwise added to the solution at 15° C. or lower, then stirred at room temperature for 90 minutes, and disappearance of the starting materials was confirmed through gas chromatography. The formed salt was filtered and washed with 30 ml of a saturated saline solution. The organic layer was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (ethyl acetate/hexane=1/1 for elution) to give 111.9 g (yield 93%) of the intended 2-propynyl 2-(diethoxyphosphoryl)acetate. The obtained 2-propynyl 2-(diethoxyphosphoryl)acetate was analyzed through 1H-NMR to confirm the structure thereof. The results are shown below. The formed salt was filtered washed with 30 ml of a saturated saline solution The organic layer was concentrated under reduced pressure the resulting residue was purified through silica gel column chromatography (ethyl acetate/hexane=1/1 for elution)

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

Procedure: Pyridine (3.7 ml, 45.7 mmol) is added to a solution of 2-amino-4-chlorobenzaldehyde (6.18 g, 39.7 mmol) in 170 ml of anhydrous toluene, followed dropwise by a solution of chlorocarbonylmethylphosphonic acid diethyl ester (9.8 g, 45.7 mmol) in 15 ml of anhydrous toluene whilst maintaining the reaction mixture at a temperature of less than 30° C. When the addition is complete, the mixture is stirred for 1 hour at room temperature. The reaction mixture is washed several times with water and then with a 1N HCl solution, and then again with water. Finally the mixture is washed with an aqueous saturated NaCl solution. The organic phase is dried over MgSO4, and filtration is carried out, followed by evaporation to obtain the expected crude product in the form of an orange oil. The crude product is used in the following step. whilst maintaining the reaction mixture at a temperature of less than 30° C When the addition The reaction mixture is washed several times with water Finally the mixture is washed with an aqueous saturated NaCl solution The organic phase is dried over MgSO4, and filtration followed by evaporation

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

Procedure: A solution of (diethoxyphosphoryl)acetyl chloride (480 mg, 2.2 mmol) in dry tetrahydrofuran (10 ml) was added to a mixture of 1-(2,4-dimethoxybenzyl)-3-hydrazinobenzo[f]quinoxalin-2(1H)-one (750 mg, 2 mmol) and dry triethylamine (220 mg, 2.2 mmol) in dry tetrahydrofuran (40 ml). The mixture was stirred at room temperature for 1.5 h and filtered. The filtrate was evaporated to give 1.1 g of the title compound as a crude product. filtered The filtrate was evaporated

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

Procedure: A solution of (diethoxyphosphoryl)acetyl chloride (480 mg, 2.2 mmol) in dry tetrahydrofuran (10 ml) was added to a mixture of 1-(2,4-dimethoxybenzyl)-3-hydrazinobenzo[f]quinoxalin-2(1H)-one (750 mg, 2 mmol) and dry triethylamine (220 mg, 2.2 mmol) in dry tetrahydrofuran (40 ml). The mixture was stirred at room temperature for 1.5 h and filtered. The filtrate was evaporated to give 1.1 g of the title compound as a crude product. filtered The filtrate was evaporated

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

Procedure: The title compound was prepared from 2,6-dichloro-3-hydrazinoquinoxaline (830 mg, 3.62 mmol) and (diethoxyphosphoryl)acetyl chloride (800 mg, 3.72 mmol) by the method described in example 13 (619 mg; 44%). M.p. 223°-227° C. (ethanol); 1H-NMR (DMSO-d6): δ 1.19 (t, 6H), 4.07 (quint: 4H), 4.32 (d, 2H), 7.39 (d, 1H), 7.56 (dd, 1H), 8.19 (d, 1H), 12.2 (s, 1H).

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

Procedure: A solution of (diethoxyphosphoryl)acetyl chloride (2.15 g, 10 mmol) in 20 ml of dry tetrahydrofuran was added to a solution of 3-chloro-6-cyano-2-hydrazinoquinoxaline (2.0 g, 9 mmol) and dry triethylamine (1.4 ml, 10 mmol) in 100 ml of dry tetrahydrofuran. The mixture was stirred at room temperature overnight, and filtered. The filtrate was evaporated, and the title compound was isolated as a semisolid residue, which was used in the next step without further purification; 1H-NMR (DMSO-d6): δ 1.26 (t, 6H), 3.09 (d, 2H), 4.10 (quint, 4H), 7.71 (d, 1H), 7.97 (dd, 1H), 8.39 (d, 1H). filtered The filtrate was evaporated

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

Procedure: A solution of (diethoxyphosphoryl)acetyl chloride (2.15 g, 10 mmol) in 20 ml of dry tetrahydrofuran was added to a solution of 3-chloro-6-cyano-2-hydrazinoquinoxaline (2.0 g, 9 mmol) and dry triethylamine (1.4 ml, 10 mmol) in 100 ml of dry tetrahydrofuran. The mixture was stirred at room temperature overnight, and filtered. The filtrate was evaporated, and the title compound was isolated as a semisolid residue, which was used in the next step without further purification; 1H-NMR (DMSO-d6): δ 1.26 (t, 6H), 3.09 (d, 2H), 4.10 (quint, 4H), 7.71 (d, 1H), 7.97 (dd, 1H), 8.39 (d, 1H). filtered The filtrate was evaporated