2-(2-氧代吡咯烷-1-基)乙基 甲磺酸盐

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of methyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate (0.8 g, 3.5 mmol) in DMF (10 ml) was added NaH (0.28 g, 7 mmol) followed by the addition of 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate (0.7 g, 3.5 mmol). The mixture was then stirred overnight at RT. Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate. Ethyl acetate layer was separated, dried over anhydrous sodium sulfate and evaporated to yield 0.5 g of methyl 5-methyl-4-oxo-3-(2-(2-oxopyrrolidin-1-yl)ethyl)-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate, as an oil (yield: 42.8%). Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate Ethyl acetate layer was separated dried over anhydrous sodium sulfate evaporated

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

实验步骤: To a solution of methyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate (0.8 g, 3.5 mmol) in DMF (10 ml) was added NaH (0.28 g, 7 mmol) followed by the addition of 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate (0.7 g, 3.5 mmol). The mixture was then stirred overnight at RT. Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate. Ethyl acetate layer was separated, dried over anhydrous sodium sulfate and evaporated to yield 0.5 g of methyl 5-methyl-4-oxo-3-(2-(2-oxopyrrolidin-1-yl)ethyl)-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate, as an oil (yield: 42.8%). Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate Ethyl acetate layer was separated dried over anhydrous sodium sulfate evaporated

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 1-(2-hydroxyethyl)pyrrolidin-2-one (2.6 g, 20 mmol) in pyridine (15 ml) was added methanesulfonyl chloride (2.28 g, 20 mmol) and the reaction mixture was stirred at RT overnight. Solution was concentrated and diluted with ethyl acetate (50 ml) and washed with water (50 ml). Ethyl acetate layer was separated, dried over anhydrous sodium sulfate and evaporated to yield 3.0 g of 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate, as an oil (yield: 75%). Solution was concentrated diluted with ethyl acetate (50 ml) washed with water (50 ml) Ethyl acetate layer was separated dried over anhydrous sodium sulfate evaporated

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

实验步骤: The 1-(2-hydroxyethyl)-2-pyrrolidinone (Aldrich, 0.16 g, 1.2 mmol), triethylamine (0.56 mL, 4.1 mmol), and methanesulfonyl chloride (0.15 mL, 1.9 mmol) in 10 mL THF were processed as described in Example 1C to give the title compound that was used directly in the next reaction.

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

实验步骤: The 1-(2-hydroxyethyl)-2-pyrrolidinone (Aldrich, 0.16 g, 1.2 mmol), triethylamine (0.56 mL, 4.1 mmol), and methanesulfonyl chloride (0.15 mL, 1.9 mmol) in 10 mL THF were processed as described in Example 1C to give the title compound that was used directly in the next reaction.

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: The 1-(2-hydroxyethyl)-2-pyrrolidinone (Aldrich, 0.16 g, 1.2 mmol), triethylamine (0.56 mL, 4.1 mmol), and methanesulfonyl chloride (0.15 mL, 1.9 mmol) in 10 mL THF were processed as described in Example 1C to give the title compound that was used directly in the next reaction.

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

实验步骤: The 1-(2-hydroxyethyl)-2-pyrrolidinone (Aldrich, 0.16 g, 1.2 mmol), triethylamine (0.56 mL, 4.1 mmol), and methanesulfonyl chloride (0.15 mL, 1.9 mmol) in 10 mL THF were processed as described in Example 1C to give the title compound that was used directly in the next reaction.

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6-fluoro-1-(phenylsulfonyl)-3-(1H-pyrazol-4-yl)-1H-indole (Intermediate 5; 443 mg; 1.30 mmol), 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate (Intermediate 43; 400 mg; 1.93 mmol), Cs2CO3 (1.30 g; 3.99 mmol) in DMF (10 mL) was stirred at 90° C. overnight. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (40 mL×3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated to afford 285 mg (48%) of the title compound as a brown solid, which was used directly used without further purification. extracted with EtOAc (40 mL×3) The combined organic layers were washed with brine (30 mL) dried over anhydrous Na2SO4 filtered concentrated

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

实验步骤: Following the general method as outlined in Intermediate 31, starting from 1-(2-hydroxyethyl)pyrrolidin-2-one (500 mg; 3.87 mmol), 400 mg (50%) of the title compound as a yellow oil, which was used directly without further purification.

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

实验步骤: To a solution of methyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate (0.8 g, 3.5 mmol) in DMF (10 ml) was added NaH (0.28 g, 7 mmol) followed by the addition of 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate (0.7 g, 3.5 mmol). The mixture was then stirred overnight at RT. Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate. Ethyl acetate layer was separated, dried over anhydrous sodium sulfate and evaporated to yield 0.5 g of methyl 5-methyl-4-oxo-3-(2-(2-oxopyrrolidin-1-yl)ethyl)-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate, as an oil (yield: 42.8%). Reaction was quenched with water (10 ml) and mixture extracted with ethyl acetate Ethyl acetate layer was separated dried over anhydrous sodium sulfate evaporated