肌氨酸乙酯 盐酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of (tert-butoxycarbonyl-methyl-amino)-acetic acid (37 g, 0.2 mol) and Et3N (60.6 g, 0.6 mol) in CH2Cl2 (300 mL) was added isobutyl chloroformate (27.3 g, 0.2 mmol) dropwise at −20° C. under argon. After stirring for 0.5 h, methylamino-acetic acid ethyl ester hydrochloride (30.5 g, 129 mmol) was added dropwise at −20° C. The mixture was allowed to warm to room temperature (c.a. 1 h) and quenched with water (500 mL). The organic layer was separated, washed with 10% citric acid solution, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (petroleum ether/EtOAc 1:1) to give {[2-(tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetic acid ethyl ester (12.5 g, 22%). quenched with water (500 mL) The organic layer was separated washed with 10% citric acid solution dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (petroleum ether/EtOAc 1:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-Methyl glycine ethyl ester hydrochloride (255 mg, 1.66 mmol) was added to a suspension of 5-(4-tert-butylphenyl)-3-formyl-1-(4-isopropoxyphenyl)indole-2-carboxylic acid ethyl ester (400 mg, 0.83 mmol; see step (c) above) in MeOH (20 mL) and the pH was adjusted to 6 by the addition of a few drops of glacial acetic acid. After 1 h at rt, NaCNBH3 (75 mg, 1.18 mmol) was added and the mixture was stirred at rt for 24 h, poured into H2O and extracted with EtOAc. The combined extracts were washed with H2O and brine, dried (Na2SO4), concentrated and purified by chromatography to give the sub-title compound. Yield 400 mg (87%). extracted with EtOAc The combined extracts were washed with H2O and brine dried (Na2SO4) concentrated purified by chromatography

反应条件: temp:92.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 125 mL round-bottomed flask equipped with condenser and nitrogen inlet were added 486 mg (1.20 mmol) 3-phenyl-3-[4-(3-trifluoromethyl-phenoxy)-phenoxy]-1-chloropropane, 184 mg (1.20 mmol) sarcosine ethyl ester hydrochloride, 0.416 mL (2.40 mmol) diisopropylethylamine, and 6 mL dry N-methylpyrrolidinone. The reaction was heated at 90-95° C. for 60 h, cooled, and poured into water. After extracting with ethyl acetate, the organic layer was washed with water (3 times) and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methylene chloride/methanol as eluant to afford 250 mg (43%) of an oil. To a 125 mL round-bottomed flask equipped with condenser and nitrogen inlet cooled After extracting with ethyl acetate the organic layer was washed with water (3 times) and brine dried over sodium sulfate evaporated The residue was chromatographed on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of (tert-butoxycarbonyl-methyl-amino)-acetic acid (37 g, 0.2 mol) and Et3N (60.6 g, 0.6 mol) in CH2Cl2 (300 mL) was added isobutyl chloroformate (27.3 g, 0.2 mmol) dropwise at −20° C. under argon. After stirring for 0.5 h, methylamino-acetic acid ethyl ester hydrochloride (30.5 g, 129 mmol) was added dropwise at −20° C. The mixture was allowed to warm to room temperature (c.a. 1 h) and quenched with water (500 mL). The organic layer was separated, washed with 10% citric acid solution, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (petroleum ether/EtOAc 1:1) to give {[2-(tert-butoxycarbonyl-methyl-amino)-acetyl]-methyl-amino}-acetic acid ethyl ester (12.5 g, 22%). quenched with water (500 mL) The organic layer was separated washed with 10% citric acid solution dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (petroleum ether/EtOAc 1:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared by the procedure described in Example 1 using 9.18 g of 4-chloro-2-methylphenyl-isothiocyanate, 7.68 g of sarcosine ethyl ester hydrochloride, 12.0 g of triethyl amine, and 300 mL of chloroform. Crystallization from diethyl ether afforded the title compound (7.5 g) as an off-white solid, m.p. 113°-115° C. Anal. Calcd. for C11H11Cl N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.72; H, 4.17; N, 10.88. Mass spectrum (EI, M.+) m/z 254/256. The title compound was prepared by the procedure Crystallization from diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared by the procedure described in Example 1 using 18.3 g of 3-chloro-4-methylphenyl-isothiocyanate, 15.3 g of sarcosine ethyl ester hydrochloride, 25 g of triethyl amine, and 300 mL of chloroform. Crystallization from ethyl acetate afforded the title compound (14.5 g) as an off-white solid, m.p. 178°-180° C. Anal. Calcd. for C11H11Cl N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.89; H, 4.20; N, 10.95. Mass spectrum (+FAB, [M+H]+) m/z 255/257. The title compound was prepared by the procedure Crystallization from ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared by the procedure described in Example 1 using 13.2 g of 3-chloro-2-methylphenyl-isothiocyanate, 11.0 g of sarcosine ethyl ester hydrochloride, 25 g of triethyl amine, and 300 mL of chloroform. Crystallization from diethyl ether afforded the title compound (15.2 g) as a tan solid, m.p. 122°-124° C. Anal. Calcd. for C11H11Cl N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.96; H, 4.21; N, 11.05. Mass spectrum (EI, M.+) m/z 254/256. The title compound was prepared by the procedure Crystallization from diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of sarcosine ethyl ester hydrochloride (7.68 g), 5 -chloro-2-methylphenyl-isothiocyanate (9.18 g), triethyl amine (12 g) and chloroform (200 mL) was heated at reflux for 5 hours. The mixture was cooled to ambient temperature, washed with 1N HCl(2×200 ), then with water (200 mL) The organic phase was evaporated to dryness. The residue was crystallized from ethanol to give the tide compound (9.2 g) as a tan solid, m.p. 132°-134° C. Anal. Calcd. for C11H11 Cl N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.79; H, 4.12; N, 10.73. Mass spectrum (EI, M.+) m/z 254/256. was heated at reflux for 5 hours washed with 1N HCl(2×200 ) with water (200 mL) The organic phase was evaporated to dryness The residue was crystallized from ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of a-formyl-2,4,6 trimethylphenylacetonitrile (4.5 g, 24 mmol) and sarcosine ethyl ester hydrochloride (3.7 g, 24 mmol) in 100 mL of benzene was refluxed in a Dean-Stark apparatus for 16 h. The solvent was removed in vacuo to afford N-Methyl-N-[2-(2,4,6-trimethylphenyl)-2-cyanovinyl]-glycine ethyl ester as a pale yellow oil. was refluxed in a Dean-Stark apparatus for 16 h The solvent was removed in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-(4-fluorobenzoyl)benzoic acid (3.00 g), 1-hydroxybenzotriazole (2.07 g), 1,3-dicyclohexylcarbodiimide (3.00 g) and anhydrous THF (50 ml) was stirred at room temperature for 1 hour. To this mixture were added N-methylglycine ethyl ester hydrochloride (2.84 g) and triethylamine (2.58 ml), followed by stirring at room temperature for 16 hours and with heating and refluxing for 4 hours. After the solvent was distilled off, ethyl acetate was added to the residue, and the insoluble crystals were separated by filtration. The filtrate was washed successively with water, aqueous sodium hydrogen carbonate, water, dilute hydrochloric acid and water and then dried, after which the solvent was distilled off, to yield N-[2-(4-fluorobenzoyl)benzoyl]-N-methylglycine ethyl ester as a colorless oily substance (4.2 g). by stirring at room temperature for 16 hours with heating refluxing for 4 hours After the solvent was distilled off ethyl acetate was added to the residue the insoluble crystals were separated by filtration The filtrate was washed successively with water, aqueous sodium hydrogen carbonate, water, dilute hydrochloric acid and water dried after which the solvent was distilled off

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 840 ml (6.1 Mol) triethylamine is added to a solution of 759 g (1.2 Mol) 3,5-diacetamido-2,4,6-triiodobenzoyl chloride and 276 g (1.8 Mol) sarcosine ethyl ester hydrochloride in 7600 ml N,N-dimethylformamide and stirred for 1 hr. at 60° C. The reaction mixture is cooled to room temperature, the crystallized triethyl ammonium chloride is filtered, washed with N,N-dimethylformamide and reduced under vacuum in a rotary evaporator. The residue is dissolved in 650 ml methanol and added dropwise to 3 l ethyl acetate. The precipitate is crystallized overnight, filtered to a dry state and finally washed with water, 1N hydrochloric acid, cold saturated sodium bicarbonate, water and dried under vacuum at 60° C. Yield: 685 g (80%). at 60° C the crystallized triethyl ammonium chloride is filtered washed with N,N-dimethylformamide reduced under vacuum in a rotary evaporator The residue is dissolved in 650 ml methanol added dropwise to 3 l ethyl acetate The precipitate is crystallized overnight filtered to a dry state finally washed with water, 1N hydrochloric acid, cold saturated sodium bicarbonate, water dried under vacuum at 60° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2.30 g of sarcosine ethyl ester hydrochloride was added over 5 minutes to a mixture of 2.10 g of 34A, 1.52 g of triethylamine and 60 mL of methylene chloride, under nitrogen at 25°-30° C. The mixture was stirred at room temperature for 24 hours, then diluted with 100 mL of methylene chloride, washed with water, then brine, dried (MgSO4) and stripped of solvent. The residue was dissolved in 70 mL of a 1:1 v:v mixture of ethanol and 2N hydrochloric acid. The solution was refluxed for 4 hours, the resulting mixture was stirred at room temperature overnight, stripped of volatiles, diluted with water and extracted with methylene chloride. The extract was dried (MgSO4) and stripped of solvent. The residue was purified by flash chromatography over silica gel with a 1:2 v:v mixture of hexane and ethyl acetate as eluent to give the title compound, as a glass/sticky solid. washed with water brine, dried (MgSO4) The residue was dissolved in 70 mL of a 1:1 v v mixture of ethanol and 2N hydrochloric acid The solution was refluxed for 4 hours the resulting mixture was stirred at room temperature overnight diluted with water extracted with methylene chloride The extract was dried (MgSO4) The residue was purified by flash chromatography over silica gel with a 1:2 v v mixture of hexane and ethyl acetate as eluent