2-bromopropanamide

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 25.3 g of 4-(2,4-dichlorobenzyl)-phenol and 15.2 g of α-bromopropionic acid amide in 100 ml of dimethyl formamide was stirred for 2 hours at 100° C together with 16 g of potassium carbonate. After cooling, the reaction mixture was poured into 1 liter of water. A viscous oil precipitated which was absorbed in methylene chloride and washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The remaining colorless crystals were recrystallized from methanol. Yield: 25.8 g; melting point 148° - 149° C. ##STR5## After cooling A viscous oil precipitated which was absorbed in methylene chloride washed with water After drying over sodium sulfate the solvent was distilled off under reduced pressure The remaining colorless crystals were recrystallized from methanol

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

Procedure: The title compound was prepared in analogy to Example 10 from 7-(3-fluoro-benzyloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride [Example 1c)] and (RS)-2-bromo-propionamide with potassium carbonate as the base. Yield: 85% of theory as a white solid; MS: m/e=343 (M+H)+.

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

Procedure: 5-(2-Cyano-4-fluorophenoxy)-2-(methylthio)phenol (0.05 mole) potassium carbonate (0.2 mole), 2-bromopropionamide (0.08 mole) and dimethylsulfoxide (200 ml) are charged into a 500 ml glass reaction flask equipped with a mechanical stirrer. The reaction mixture is stirred at room temperature for a period of about 8 hours. After this time the mixture is poured into 500 ml of water. The resulting mixture is extracted three times with 100 ml portions of methylene chloride. The extracts are then combined, washed with water and thereafter dried. The dried solution is then stripped of solvent under reduced pressure to leave a residue. The residue is subjected to chromatography using a clay column and hexane/ethyl acetate mixtures as the eluant. The fractions containing the product are combined and stripped of solvent to yield the desired product 2-[5-(2-cyano-4-fluorophenoxy)-2-methylthiophenoxy]propionamide as the residue. equipped with a mechanical stirrer The resulting mixture is extracted three times with 100 ml portions of methylene chloride washed with water dried to leave a residue The fractions containing the product

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Synthesized as described in Example 4 using 4-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile, 2-bromo-propionamide (2 eq) and Cs2CO3 (2 eq). After heating at 90° C. for 4 h, additional 2-bromo-propionamide (2 eq) and Cs2CO3 (2 eq) were added and the reaction mixture heated at 110° C. for 15 h: MS (ES) m/z 298 (M+1). Synthesized the reaction mixture heated at 110° C. for 15 h

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Synthesized as described in Example 4 using 4-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile, 2-bromo-propionamide (2 eq) and Cs2CO3 (2 eq). After heating at 90° C. for 4 h, additional 2-bromo-propionamide (2 eq) and Cs2CO3 (2 eq) were added and the reaction mixture heated at 110° C. for 15 h: MS (ES) m/z 298 (M+1). Synthesized the reaction mixture heated at 110° C. for 15 h

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium hydroxide (0.277 g, 4.93 mmol) and ethanol were added to a flask and stirred. 2-Bromopropionamide (0.5 g, 3.29 mmol) was added and the reaction mixture was stirred overnight. The mixture was filtrated and the filtrate was evaporated to dryness. 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawensson's reagent) (0.665 g, 1.643 mmol) and THF were added to the evaporation residue and the mixture was heated to 60° C. for 2 h. The reaction mixture was evaporated to dryness. 3-Bromopyruvic acid (0.604 g, 3.62 mmol) and THF were added to the evaporation residue and the mixture was heated to 60° C. for 3 h. The reaction mixture was cooled to RT and evaporated to dryness. The product was purified by Flash-chromatography. Yield 102%. 1H-NMR (400 MHz; DMSO): δ 1.16 (t, 3H), 1.46 (d, 3H), 3.79-3.86 (m, 2H), 4.78 (q, 1H), 8.42 (s, 1H). the reaction mixture was stirred overnight The mixture was filtrated the filtrate was evaporated to dryness The reaction mixture was evaporated to dryness the mixture was heated to 60° C. for 3 h The reaction mixture was cooled to RT evaporated to dryness The product was purified by Flash-chromatography

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5.0 g 3-bromobenzenethiol and 5.96 g potassium carbonate in 50 ml DMF were added 3.86 g 2-bromopropionamide at RT. The mixture was warmed up and stirred at 70° C. for 3.5 hrs. After cooling, 200 ml water were added and the mixture extracted 3 times with dichloromethane. Drying and evaporation of the organic phases yielded 6.5 g of the title product which was used without further purification. The mixture was warmed up After cooling the mixture extracted 3 times with dichloromethane Drying evaporation of the organic phases