carboxymethyl(trimethyl)azanium

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The operation is carried out as in Preparation 1 (Method 2) starting from 270 mg of the phenol prepared in Stage A, 309 mg of 1,1-dimethyl-ethyl N-[(phenylmethoxy)carbonyl]-L-homoserinate and 616 mg of betaine. 320 mg of expected product is obtained. The operation is carried out as in Preparation 1 (Method 2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10 parts of the betaine of 1-methyl-3-hydroxy-4,5-dichloropyridazinium salt: ##STR81## is boiled in 100 parts of thionyl chloride for two hours with an addition of 1 part of dimethylformamide. 9.5 parts (72.7% of theory) of 1-methyl-3,4,5-trichloropyridazinium chloride is obtained; C5H4N2Cl4, washed with acetonitrile.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10 parts of the betaine of 1-methyl-3-hydroxy-4,5-dichloropyridazinium salt: ##STR81## is boiled in 100 parts of thionyl chloride for two hours with an addition of 1 part of dimethylformamide. 9.5 parts (72.7% of theory) of 1-methyl-3,4,5-trichloropyridazinium chloride is obtained; C5H4N2Cl4, washed with acetonitrile.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The operation is carried out as in Preparation 1 (Method 2) starting from 270 mg of the phenol prepared in Stage A, 309 mg of 1,1-dimethyl-ethyl N-[(phenylmethoxy)carbonyl]-L-homoserinate and 616 mg of betaine. 320 mg of expected product is obtained. The operation is carried out as in Preparation 1 (Method 2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: maintaining the reaction solution from step (1) at pH 7.5-10, as necessary, by addition of a molar excess of liquid trimethylamine, to effect the formation of betaine and trimethyl ammonium hydrochloride until substantially all of the monochloroacetic acid has been reacted, leaving a residual amount of trimethylammoniumchloroacetate in the reaction solution; has been reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: maintaining the reaction solution from step (1) at pH 7.5-10, as necessary, by addition of a molar excess of liquid trimethylamine, to effect the formation of betaine and trimethyl ammonium hydrochloride until substantially all of the monochloroacetic acid has been reacted, leaving a residual amount of trimethylammoniumchloroacetate in the reaction solution; has been reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: maintaining the reaction solution from step (1) at pH 7.5-10, as necessary, by addition of a molar excess of liquid trimethylamine, to effect the formation of betaine and trimethyl ammonium hydrochloride until substantially all of the monochloroacetic acid has been reacted, leaving a residual amount of trimethylammoniumchloroacetate in the reaction solution; has been reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: maintaining the reaction solution from step (1) at pH 7.5-10, as necessary, by addition of a molar excess of liquid trimethylamine, to effect the formation of betaine and trimethyl ammonium hydrochloride until substantially all of the monochloroacetic acid has been reacted, leaving a residual amount of trimethylammoniumchloroacetate in the reaction solution; has been reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: [3H]GABA3 (98.9 Ci/mmole) was obtained from New England Nuclear (Boston, Mass.). β-alanine, betaine and L-DABA (L-(2,4) diaminobutyric acid) were from Sigma Chemical Company (St. Louis, Mo.); guvacine, nipecotic acid, OH-nipecotic (hydroxynipecotic acid), and THPO (4,5,6,7-tetrahydroisoxazolo (4,5-c]pyridin-3-ol) were from RBI (Natick, Mass.). ACHC (cis-3-aminocyclohexanecarboxylic acid) was kindly provided by Drs. Richard Milius and William White of the NIgH Chemical Synthesis Program.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: [3H]GABA3 (98.9 Ci/mmole) was obtained from New England Nuclear (Boston, Mass.). β-alanine, betaine and L-DABA (L-(2,4) diaminobutyric acid) were from Sigma Chemical Company (St. Louis, Mo.); guvacine, nipecotic acid, OH-nipecotic (hydroxynipecotic acid), and THPO (4,5,6,7-tetrahydroisoxazolo (4,5-c]pyridin-3-ol) were from RBI (Natick, Mass.). ACHC (cis-3-aminocyclohexanecarboxylic acid) was kindly provided by Drs. Richard Milius and William White of the NIgH Chemical Synthesis Program.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-(4-Ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (300 mg, 0.90 mmol) was dissolved in THF (10 ml), 2-bromoethanol was added (225 mg, 1.80 mmol) followed by betaine (738 mg, 1.80 mmol), and the mixture was stirred at room temperature for 3 hours. A further 0.5 equivalents of betaine (0.45 mmol, 162 mg) was added and the mixture was stirred at room temperature for a further hour. Mixture was partitioned between ethyl acetate (20 ml) and water (20 ml). Organics were dried and evaporated then flash chromatographed over silica (10 g Combiflash cartridge, DCM to 1% methanol in DCM) to afford a white solid which was mixture of N-1 and N-3 alkylated products. Mixture was flash chromatographed over silica (10 g Flashmaster cartridge, toluene to 20% ethyl acetate in toluene) to afford 130 mg of 1-(2-bromo-ethyl)-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile as a white solid. 1H NMR (DMSO) δ 8.80 (s, 1H), 8.74 (s, 1H), 8.48-8.39 (m, 2H), 7.44 (d, 1H), 4.88 (t, 2H), 4.29 (q, 2H), 4.05 (t, 2H), 1.40 (t, 3H). the mixture was stirred at room temperature for a further hour Mixture was partitioned between ethyl acetate (20 ml) and water (20 ml) Organics were dried evaporated flash chromatographed over silica (10 g Combiflash cartridge, DCM to 1% methanol in DCM) to afford a white solid which mixture of N-1 and N-3 alkylated products chromatographed over silica (10 g Flashmaster cartridge, toluene to 20% ethyl acetate in toluene)

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A fermentor equipped for continuous culture which contained 1.5 l of a vitamin containing mineral medium (according to Example 1) with 1.5 percent of betaine and 1.0 percent of γ-butyrobetaine-chloride was inoculated with 150 ml of strain 13 (DSM 2903) preculture of the same medium. After 20 hours of aerobic cultivation at 30° C. and pH 7.0, the culture had grown up and the continuous operation was started at a flow rate of 0.1 l/h. The culture solution flowing out of the fermentor was caught in a vessel cooled at 4° C. the cells were removed by centrifugation. According to enzymatic analysis, the supernatant contained 8.8 g of L-carnitine per 1 of culture. This corresponded to a yield of 99.2 percent (proven analytically), calculated on the concentration of the γ-butyrobetaine-chloride used. The solid L-carnitine chloride was isolated from the solution by means of ion chromatography and water separation. A fermentor equipped for continuous culture which was caught in a vessel were removed by centrifugation