1,1,3,3-tetramethylurea

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: A solution of 15 g. of the lithium salt of 3,5-heptanedione (prepared as described in Example 8 below) in 100 ml. of tetramethylurea was stirred under nitrogen at room temperature, and 10 g. of 3-ethyl-6-(3,4-methylenedioxyphenyl)-3-hexenyl iodide (Preparation D1) was added. The reaction mixture was stirred for forty-eight hours, then concentrated to remove the solvent, and the residue slurried in ether and treated with excess glacial acetic acid. Water was added, the ether layer separated, washed with water and concentrated. The residue was distilled in a molecular still to remove volatile material at 110° C. (0.001 mml.), and the non-volatile residue was chromatographed on 10 g. of activated magnesium silicate in benzene solution and eluted with ethyl acetate to give 4-[3-ethyl-6-(3,4-methylenedioxyphenyl)-3-hexenyl]-3,5-heptanedione as a yellow oil. concentrated to remove the solvent the residue slurried in ether and treated with excess glacial acetic acid Water was added the ether layer separated washed with water concentrated The residue was distilled in a molecular still to remove volatile material at 110° C. (0.001 mml.) the non-volatile residue was chromatographed on 10 g of activated magnesium silicate in benzene solution and eluted with ethyl acetate

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-5-methylimidazo[1,2-a]pyridine-2-carboxylic acid hydrochloride (0.63 g, 2.2 mmol) (this material contained sodium chloride from the previous step) in N,N-dimethylformamide (6 mL) was treated with N,N-diisopropylethylamine (1.9 mL, 11 mmol) followed by O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and stirred at 20° C. for 5 min. The reaction mixture was treated with N,O-dimethylhydroxylamine hydrochloride (0.28 g, 2.8 mmol) and stirred at 20° C. for 2 h. The reaction mixture was poured into saturated sodium bicarbonate (100 mL) and extracted with ethyl acetate (100 mL). The aqueous phase was separated, saturated with sodium chloride, and extracted with additional ethyl acetate (100 mL). The combined organic extracts were washed with brine (100 mL), dried with sodium sulfate, filtered, and concentrated to a crude oil. Purification by flash column chromatography gave the desired product that also contained N,N-dimethylformamide and tetramethyl urea. This material was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (20 mL), dried with sodium sulfate, filtered, and concentrated to give 0.55 g of the desired product as a white solid. The aqueous layer, which still contained desired product, was concentrated and the resultant residue was purified by preparative LCMS to give an additional 42 mg of the desired product. The total amount isolated was 0.59 g (91%). LCMS for C11H13BrN3O2 (M+H)+: m/z=298.0, 300.0. stirred at 20° C. for 2 h extracted with ethyl acetate (100 mL) The aqueous phase was separated, saturated with sodium chloride extracted with additional ethyl acetate (100 mL) The combined organic extracts were washed with brine (100 mL) dried with sodium sulfate filtered concentrated to a crude oil Purification by flash column chromatography

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

Procedure: A mixture of 1.80 g (12.68 mmol) phosphorus pentoxide, 1.73 g (12.6 mmol) triethylamine hydrochloride, and 1.529 g (12.6 mmol) 3,4-dichloromethylaniline is heated and stirred in a nitrogen atmosphere at 200° C. until a homogeneous melt has formed. To the melt, 1 g (4.2 mmol) of 4-(4-pyridylmethyl)-1(2H)-phthalazinone (for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) is added and the mixture stirred for 4 h at 200° C. After slight cooling, 4 ml tetramethylurea is added to the reaction mixture, followed by 2 ml water at about 120° C. The solution obtained is then distributed between dichloromethane and a mixture of 20 ml water and 5 ml conc. ammonia, and the organic phase dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. Double recrystallization of the residue from acetonitrile and drying under HV (8 h, 120° C.) yields title compound; m.p. 180-181° C.; ESI-MS: (M+H)+=341. is heated has formed the mixture stirred for 4 h at 200° C The solution obtained the organic phase dried over anhydrous sodium sulfate filtered evaporated under vacuum Double recrystallization of the residue from acetonitrile drying under HV (8 h, 120° C.)