1-pyrrolidin-1-ylprop-2-en-1-one

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml ) was added, the layers were separated and the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml ) was added, the layers were separated and the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica

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

Procedure: 7.5 parts of exemplified compound 1-1, compound represented by Formula (I), and 2.5 parts of N-acryloylpyrrolidine were dissolved in 8 parts of ethyl acetate. 0.033 parts of 2-mercaptoethanol was added to the resultant solution. Polymerization was carried out in the presence of 0.02 parts of 2,2′-azobis(2,4-dimethylvaleronitrile) (V-65™ manufactured by Wako Pure Chemical Industries, Ltd.,) serving as a polymerization initiator at a surrounding temperature of 70° C. for 7 hours under nitrogen flow. After the completion of the polymerization, the resultant polymer solution was added to 100 parts of hexane to precipitate a product. As a result, 9.5 parts of exemplified polymer 2-18 was be produced by radical polymerization of the above-mentioned compound 1-1 and N -acryloylpyrroline (yield: 95%). Polymerization After the completion of the polymerization to precipitate a product

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml) was added, the layers were separated and the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml) was added, the layers were separated and the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: DIPEA (1.44 ml, 8.36 mmol) was added to a solution of 125a (650 mg, 2.09 mmol), 125b (287 mg, 2.29 mmol), Pd-(OAc)2 (46 mg, 0.21 mmol) and P(o-tol)3 (127 mg, 0.42 mmol) in propionitrile/DMF (8 ml/2 ml) and the reaction mixture was purged with nitrogen for 10 minutes, then was heated at 110° C. for 16 h. The progress of the reaction was monitored by TLC. After 16 h of stirring, the mixture was cooled to 20-35° C. and filtered on celite. The filtrate was concentrated and resultant residue diluted with water (30 ml) and extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with brine (30 ml), followed by drying over anhydrous Na2SO4 and filtering. The filtrate was rotary evaporated to get residue which was purified by column chromatography using a mixture of 50% ethyl acetate/pet ether as an eluent to get the desired compound as an off-white solid (400 mg, 54%). 1H NMR (400 MHz, DMSO-d6) δ 7.50 (d, J=6.8 Hz, 2H), 7.41 (d, J=15.7 Hz, 1H), 7.20 (d, J=8.3 Hz, 1H), 6.94 (d, J=15.7 Hz, 1H), 4.56-4.46 (m, 2H), 3.63 (t, J=6.6 Hz, is 2H), 3.55 (t, J=5.9 Hz, 2H), 3.41-3.34 (m, 2H), 2.79 (t, J=5.9 Hz, 2H), 1.96-1.88 (m, 2H); 1.87-1.76 (m, 2H), 1.43 (s, 9H). the reaction mixture was purged with nitrogen for 10 minutes the mixture was cooled to 20-35° C. filtered on celite The filtrate was concentrated resultant residue diluted with water (30 ml) extracted with ethyl acetate (2×30 ml) The combined organic layers were washed with brine (30 ml) by drying over anhydrous Na2SO4 filtering The filtrate was rotary evaporated to get residue which was purified by column chromatography a mixture of 50% ethyl acetate/pet ether as an eluent

Conditions: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of pyrrolidine (2 g, 28.16 mmol) in anhydrous DCM (30 ml) was added triethylamine (15.56 ml, 111.88 mmol) and acryloyl chloride (3.04 g, 33.77 mmol) at 0° C. The reaction mixture was stirred at 20-35° C. for 16 h. The progress of the reaction was monitored by TLC. After 16 h of stirring, the reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers was washed with brine (50 ml), followed by drying over anhydrous Na2SO4 and filtering. The filtrate was rotary evaporated to get the desired compound as a brown liquid (1.1 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ 6.49-6.33 (m, 2H), 5.66 (dd, J=9.8, 2.4 Hz, 1H), 3.54 (dt, J=6.8, 3.9 Hz, 4H), 2.02-1.91 (m, 2H), 1.90-1.82 (m, 2H). After 16 h of stirring extracted with ethyl acetate (2×50 ml) The combined organic layers was washed with brine (50 ml) by drying over anhydrous Na2SO4 filtering The filtrate was rotary evaporated

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml ) was added, the layers were separated and the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous layer extracted with ethyl ether (100 ml) and methylene chloride (2×75 ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica

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

Procedure: 7.5 parts of exemplified compound 1-1, compound represented by Formula (I), and 2.5 parts of N-acryloylpyrrolidine were dissolved in 8 parts of ethyl acetate. 0.033 parts of 2-mercaptoethanol was added to the resultant solution. Polymerization was carried out in the presence of 0.02 parts of 2,2′-azobis(2,4-dimethylvaleronitrile) (V-65™ manufactured by Wako Pure Chemical Industries, Ltd.,) serving as a polymerization initiator at a surrounding temperature of 70° C. for 7 hours under nitrogen flow. After the completion of the polymerization, the resultant polymer solution was added to 100 parts of hexane to precipitate a product. As a result, 9.5 parts of exemplified polymer 2-18 was be produced by radical polymerization of the above-mentioned compound 1-1 and N -acryloylpyrroline (yield: 95%). Polymerization After the completion of the polymerization to precipitate a product

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acryloyl chloride (9 g, 0.1 mole) was added by syringe to ethyl ether (40 ml) and the solution cooled to -50° C. A solution of pyrrolidine (7.1 g, 0.1 mole) in ethyl ether (20 ml) was added dropwise. A solution of triethylamine (15.3 ml) was added slowly over 10 minutes. The reaction was slowly allowed to warm to room temperature and stirred for 12 hours. Water (50 ml) was added, the layers were separated and the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml), and combined with the organic layer above, dried over sodium sulfate, filtered, and the solvents removed to give an oil. The product was purified by chromatography on silica. The structure was confirmed by NMR. to warm to room temperature the layers were separated the aqueous Iayer extracted with ethyl ether (100 ml) and methylene chloride (2×ml) dried over sodium sulfate filtered the solvents removed to give an oil The product was purified by chromatography on silica