2-bromo-1-(2-methoxyphenyl)ethanone

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: Methyl 4-[4-(2-Methoxyphenyl)(1,3-thiazol-2-yl)]-5-metmylthiothiophene-2-carboxylate: 105 mg (0.424 mmol) of methyl 4-(aminothioxomethyl)-5-methylthiothiophene-2-carboxylate (Maybridge Chemical Co. LTD., Cornwall, U.K.) was dissolved in 5 mL of reagent grade acetone. 2-Bromo-2′-methoxy acetophenone (0.467 mmol; 110 mg) was added and the solution was allowed to reflux for 3 h. The solution was allowed to cool and the solution concentrated. The crude product was dissolved in 100 mL of CH2Cl2 and washed one time with 50 mL of 1N NaOH. The organic layer was obtained, dried over sodium sulfate, concentrated and purified on a 1 mm silica plate eluting with 20% ethyl acetate/hexane to afford 160 mg (95% yield) of methyl 4-[4-(2-methoxyphenyl)(1,3-thiazol-2-yl)]-5-methylthiothiophene-2-carboxylate. to reflux for 3 h to cool the solution concentrated The crude product was dissolved in 100 mL of CH2Cl2 washed one time with 50 mL of 1N NaOH The organic layer was obtained dried over sodium sulfate concentrated purified on a 1 mm silica plate eluting with 20% ethyl acetate/hexane

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

Procedure: The title compound was prepared according to the procedure described in Example 57 from methyl trans 4-chloro-2-(phenylsulfonylamino)cinnamate (step 1 of Example 8, Method A) and 2-methoxyphenacyl bromide.

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

Procedure: Analogously to Step 8.1, 14.5 g (87 mmol) of 2-amidino-acetic acid ethyl ester hydrochloride in 150 ml of abs. ethanol are reacted with 5.9 g (87 mmol) of sodium ethanolate and 10.3 g (44 mmol) of 2-bromo-1-(2-methoxy-phenyl)-ethan-1-one (2-bromo-2'-methoxy-acetophenone; Aldrich; Milwaukee/USA) to form the title compound; m.p.: 128° C.; TLC-Rf =0.25 (hexane/ethyl acetate [2:1]).

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

Procedure: A solution of 41.7 g (0.257 mol) of benzaldehyde guanylhydrazone (see Thiele, A., Liebigs Annalen der Chemie 270, 35) and 30.12 g of 2-methoxyphenacyl bromide (Aldrich, Buchs, Switzerland; 98%, Cat. no. 10,085-4) in 130 ml of ethanol is boiled under reflux for one hour. After cooling, the product that has crystallised out is filtered off with suction and recrystallized from ethanol. In that manner there is obtained the title compound, m.p. 166°-167° C., 1H-NMR (DMSO): δ=8.61 (s, 1H); 8.0 (m, 3H); 7.88 (s, 1H); 7.5 (m, 3H); 7.19 (m, 1H); 7.03 (d, 1H); 6.96 (t, 1H); 6.16 (s, 2H); 3.94 (s, 3H). under reflux for one hour After cooling the product that has crystallised out is filtered off with suction recrystallized from ethanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add THF (125 mL, anhydrous) to a sealed vessel containing 5-thiocarbamoyl-pentanoic acid methyl ester (7.25 g, 41.4 mmol) and 2-bromo-2′-methoxyacetophenone (9.48 g, 41.4 mmol). Flush vessel with N2, seal, and heat at 80° C. overnight. Cool to room temperature, add EtOAc, wash with saturated aqueous NaHCO3 solution, brine, and backextract from each aqueous layer with EtOAc. Dry combined organic layers over MgSO4 and concentrate to get 18 grams of purple residue. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-20% EtOAc/hexanes to afford the title compound (9.7 g, 77%). TLC (30% EtOAc/hexanes) Rf=0.38. MS (IS) 306 (M+1)+. Flush vessel with N2 seal Cool to room temperature add EtOAc wash with saturated aqueous NaHCO3 solution, brine, and backextract from each aqueous layer with EtOAc Dry concentrate

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

Procedure: Add sodium azide (2.14 g, 32.92 mmol) to a solution of 2-bromo-2′-methoxyacetophenone (5.01 g, 21.87 mmol) in 75 ml of DMSO. Stir the mixture at ambient temperature for 18 hours and dilute it with 250 ml of water. Extract the mixture with ether (3×). Dry the combined organic layers with MgSO4. Filter off the drying agent and concentrate in vacuo to afford 3.54 g of 2-azido-1-(2-methoxyphenyl)-ethanone. Extract the mixture with ether (3×) Dry the combined organic layers with MgSO4 Filter off the drying agent concentrate in vacuo

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

Procedure: Add sodium azide (2.14 g, 32.92 mmol) to a solution of 2-bromo-2′-methoxyacetophenone (5.01 g, 21.87 mmol) in 75 ml of DMSO. Stir the mixture at ambient temperature for 18 hours and dilute it with 250 ml of water. Extract the mixture with ether (3×). Dry the combined organic layers with MgSO4. Filter off the drying agent and concentrate in vacuo to afford 3.54 g of 2-azido-1-(2-methoxyphenyl)-ethanone. Extract the mixture with ether (3×) Dry the combined organic layers with MgSO4 Filter off the drying agent concentrate in vacuo

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

Procedure: 2-Bromo-1-(2-methoxy-phenyl)-ethanone (0.6388 g, 2.789 mmol) and thiourea (0.2289 g, 3.007 mmol) were dissolved in a 20 mL of ethanol. The reaction mixture was allowed to stir overnight at room temperature. The ethanol was evaporated to dryness and the crude product was dissolved in a minimum of dichloromethane. The crude product was then extracted twice with 1M sodium hydroxide and once with a saturated aqueous solution of sodium chloride. The organic layer was then dried over sodium sulfate, filtered, and evaporated to dryness to yield the pure product (0.529 g, 2.56 mmol, 92.0%). ESI-MS m/z calc. 206.3, found 207.1 (M+1)+ Retention time 1.86 minutes. 1H NMR (400 MHz, CD3CN) δ 3.91 (s, 3H), 5.54 (s, 2H), 6.97-7.02 (m, 1H), 7.03-7.06 (m, 1H), 7.23 (s, 1H), 7.24-7.29 (m, 1H), 8.06 (dd, J=7.8, 1.8 Hz, 1H). The ethanol was evaporated to dryness the crude product was dissolved in a minimum of dichloromethane The crude product was then extracted twice with 1M sodium hydroxide and once with a saturated aqueous solution of sodium chloride The organic layer was then dried over sodium sulfate filtered evaporated to dryness

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

Procedure: A solution of 5-chloropyrimidin-2-one (541 mg) and 2-bromo-2'-methoxyacetophenone (954 mg) in triethylamine (1 ml) and ethanol (25 ml) was stirred at ambient temperature for 31/2 hours. After evaporation of solvents, the residue was dissolved in ethyl acetate (150 ml) and this solution was washed with water (50 ml) and brine (25 ml), dried (MgSO4) and evaporated to give a foam. This was purified by preparative thin-layer chromatography on silica, developed in chloroform, then chloroform-ethanol (25:1) before crystallisation from ethyl acetate to give the title pyrimidinone (347 mg,); m.p. 123°-125°; λmax 248.5 nm ε 12200), 317.5 nm (ε 6700), λinf 229.5 nm (ε 12440), 349 nm (ε 2640). After evaporation of solvents the residue was dissolved in ethyl acetate (150 ml) this solution was washed with water (50 ml) and brine (25 ml) dried (MgSO4) evaporated to give a foam This was purified by preparative thin-layer chromatography on silica chloroform-ethanol (25:1) before crystallisation from ethyl acetate