2-氨基-2-硫氧乙基特戊酸酯

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

实验步骤: To a solution of bromopyruvic acid (0.37 g, 2.22 mmol) and 2-(tert-butylcarbonyloxy)thioacetamide (0.41 g, 2.22 mmol) in ethanol (20 ml) was added 4 A molecular sieves (2 g). After stirring for 15 h, 20 mL of dichloromethane was added. The mixture was stirred 5 min and filtered to give the product as a yellow solid. The mixture was stirred 5 min filtered

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

实验步骤: To a solution of bromopyruvic acid (0.37 g, 2.22 mmol) and 2-(tert-butylcarbonyloxy)thioacetamide (0.41 g, 2.22 mmol) in ethanol (20 ml) was added 4 A molecular sieves (2 g). After stirring for 15 h, 20 mL of dichloromethane was added. The mixture was stirred 5 min and filtered to give the product as a yellow solid. The mixture was stirred 5 min filtered

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

实验步骤: 2-Chloro-1-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]ethanone (0.73 g, 2.30 mmol) and 2-(tert-butylcarbonyloxy)thioacetamide (1.21 g, 6.89 mmol) were suspended in ethanol (10 ml) and the resulting mixture subjected to microwave irradiation at 150° C. for 10 min using an Emrys™ Optimizer EXP. The reaction mixture was concentrated in vacuo and the residue obtained was purified by flash column chromatography eluting with 5% (v/v) ethyl acetate in n-heptane to afford 1-(cyclohexyl)methyl-7-methoxy-3-{2-[(tertbutylcarbonyloxy)methyl]thiazol-4-yl}-1H-indole as a yellow oil (1.01 g). irradiation at 150° C. for 10 min The reaction mixture was concentrated in vacuo the residue obtained was purified by flash column chromatography eluting with 5% (v/v) ethyl acetate in n-heptane

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-(2-Bromopropanoyl)-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (Example 53 (b), 0.06 g, 0.10 mmol), 2-amino-2-thioxoethyl pivalate (0.022 g, 0.125 mmol), EtOH (2 ml) and a magnetic stirrer bar were placed in a tube designed for microwave synthesis. The vial was sealed and the mixture was heated in a CEM Discover Microwave apparatus (100 W, 80 ° C.) for 40 minutes, giving complete conversion of the starting material to a single product according to LC-MS. The solvents were evaporated to give a crude mixture which was purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester. This compound was dissolved in THF (2 ml) and water (2 ml). To this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture was stirred at room temperature overnight. The THF was evaporated off and the water phase was acidified, extracted, and lo the extracts were evaporated. Purification by preparative HPLC gave pure fractions which were freeze-dried to give the title compound (0.040 g, 68%) as a white solid. designed for microwave synthesis The vial was sealed giving complete conversion of the starting material to a single product The solvents were evaporated to give a crude mixture which was purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester This compound was dissolved in THF (2 ml) To this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture The THF was evaporated off extracted were evaporated Purification by preparative HPLC gave pure fractions which were freeze-dried

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

实验步骤: The process is carried out as for Example 8 above, using compound A, 6-(2-bromo-acetyl)-3-(4-chlorophenyl)-1,9-dimethyl-1,9-dihydropyrido[2,3-b]indol-2-one and 2-amino-2-thioxoethyl pivalate.

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

实验步骤: The process is carried out as for Example 8 above, using compound A, 6-(2-bromo-acetyl)-3-(4-chlorophenyl)-1,9-dimethyl-1,9-dihydropyrido[2,3-b]indol-2-one and 2-amino-2-thioxoethyl pivalate.

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

实验步骤: The process is carried out as indicated in Example 3 above, with compound B 6-(2-bromoacetyl)-3-(4-fluorophenyl)-1,9-dimethyl-1,9-dihydropyrido[2,3-b]indol-2-one and 2-amino-2-thioxoethyl pivalate

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

实验步骤: This compound is prepared according to a protocol identical to that described for Stage 350.3 of Example 350, respectively using 2-(tert-butylcarbonyloxy)thioacetamide and 2-bromo-1-[10-(chloroacetyl)-10H-phenothiazin-2-yl]ethanone instead of intermediate 1.2 and bromo-1-(3,5-ditert-butyl-4-hydroxyphenyl)ethanone. The expected compound is obtained in the form of a greenish solid with a yield of 63.2%. Melting point: 120.0-122.0° C. This compound is prepared

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

实验步骤: 2-Amino-2-thioxoethyl pivalate (3.0 g, 17.12 mmol) and 3-bromo-2-oxopropanoic acid (3.14 g, 18.83 mmol) were dissolved in EtOH (20 mL), 4 Å molecular sieves added and the reaction mixture heated at reflux for 20 h then cooled to RT, filtered, washed with EtOH and evaporated in vacuo. The residual semi solid was treated with 50% EtOAc/DCM and the resulting light brown solid filtered off. The filtrate was evaporated in vacuo and the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent to afford the sub-title compound as a pale yellow oil. Yield: 2.47 g 4 Å molecular sieves added the reaction mixture heated at reflux for 20 h filtered washed with EtOH evaporated in vacuo The residual semi solid was treated with 50% EtOAc/DCM the resulting light brown solid filtered off The filtrate was evaporated in vacuo the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent

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

实验步骤: 2-Amino-2-thioxoethyl pivalate (3.0 g, 17.12 mmol) and 3-bromo-2-oxopropanoic acid (3.14 g, 18.83 mmol) were dissolved in EtOH (20 mL), 4 Å molecular sieves added and the reaction mixture heated at reflux for 20 h then cooled to RT, filtered, washed with EtOH and evaporated in vacuo. The residual semi solid was treated with 50% EtOAc/DCM and the resulting light brown solid filtered off. The filtrate was evaporated in vacuo and the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent to afford the sub-title compound as a pale yellow oil. Yield: 2.47 g 4 Å molecular sieves added the reaction mixture heated at reflux for 20 h filtered washed with EtOH evaporated in vacuo The residual semi solid was treated with 50% EtOAc/DCM the resulting light brown solid filtered off The filtrate was evaporated in vacuo the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent

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

实验步骤: 2-Amino-2-thioxoethyl pivalate (3.0 g, 17.12 mmol) and 3-bromo-2-oxopropanoic acid (3.14 g, 18.83 mmol) were dissolved in EtOH (20 mL), 4 Å molecular sieves added and the reaction mixture heated at reflux for 20 h then cooled to RT, filtered, washed with EtOH and evaporated in vacuo. The residual semi solid was treated with 50% EtOAc/DCM and the resulting light brown solid filtered off. The filtrate was evaporated in vacuo and the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent to afford the sub-title compound as a pale yellow oil. Yield: 2.47 g 4 Å molecular sieves added the reaction mixture heated at reflux for 20 h filtered washed with EtOH evaporated in vacuo The residual semi solid was treated with 50% EtOAc/DCM the resulting light brown solid filtered off The filtrate was evaporated in vacuo the residue purified by chromatography on silica with 20% EtOAc/isohexane as eluent

反应条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6 g (29.48 mmol) of 2-chloro-3,5-dinitropyridine and 7.74 g (44.22 mmol) of 2-amino-2-thioxoethyl pivalate in 50 mL of sulfolane is heated for 2 hours at 105° C. After this time, 150 mL of ethyl acetate are added to the mixture, and the organic phase is washed three times with 200 mL of water and then once with 100 mL of saturated sodium chloride solution. The organic phase is then separated out, dried over sodium sulfate and then concentrated under reduced pressure. The product obtained is purified by chromatography on a column of silica, eluting with a mixture of heptane and ethyl acetate. 1.45 g of a yellow solid are obtained. the organic phase is washed three times with 200 mL of water The organic phase is then separated out dried over sodium sulfate concentrated under reduced pressure The product obtained is purified by chromatography on a column of silica eluting with a mixture of heptane and ethyl acetate