炔丙基苯磺酸

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

实验步骤: U.S. Pat. No. 5,532,415 discloses process for preparation of R(+)-Rasagiline mesylate which comprises treating a solution of propargyl benzenesulfonate (3) and racemic aminoindan (2) in toluene with aqueous solution of 15% sodium hydroxide to get racemic Rasagiline base (4). The obtained crude racemic Rasagiline is treated with L-tartaric acid in isopropanol (IPA) to get di(R-(+)-N-propargyl-1-aminoindan)-L-tartrate (5) which is recrystallized from 1:1 methanol/isopropanol. The obtained tartrate salt is reacted with methanesulphonic acid in isopropanol at reflux to obtain R(+)-Rasagiline mesylate. The disadvantage of this process is that the scheme consists of low atom efficiency and involves several steps to obtain the final product.

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

实验步骤: To a mixture of racemic 1-aminoindan (64 g), 15% aqueous sodium hydroxide solution (141 g), water (107 mL) and toluene (192 mL) there was added propargyl benzenesulfonate (94.3 g) during 20 minutes at ambient temperature. The resulting mixture was heater to 45° C. for 4 hours, at which time the pH was confirmed to be >12(45% sodium hydroxide added if necessary) and the phases were separated. To the organic phase water (64 mL) was added and the pH was adjusted to 2 with 33% aqueous sulfuric acid. The aqueous phase was separated, diluted with water and mixed with toluene. The pH was adjusted to 6 with 25% aqueous sodium hydroxide and the phases separated. The aqueous phase was extracted again with toluene, ensuring a pH=6. The combined organic layers were concentrated in vacuo to yield 51 g of crude racemic N-propargyl-1-aminoindan as a yellow oil. to 45° C. for 4 hours the phases were separated To the organic phase water (64 mL) was added The aqueous phase was separated diluted with water mixed with toluene the phases separated The aqueous phase was extracted again with toluene The combined organic layers were concentrated in vacuo

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

实验步骤: To a mixture of racemic 1-aminoindan (64 g), 15% aqueous sodium hydroxide solution (141 g), water (107 mL) and toluene (192 mL) there was added propargyl benzenesulfonate (94.3 g) during 20 minutes at ambient temperature. The resulting mixture was heater to 45° C. for 4 hours, at which time the pH was confirmed to be >12(45% sodium hydroxide added if necessary) and the phases were separated. To the organic phase water (64 mL) was added and the pH was adjusted to 2 with 33% aqueous sulfuric acid. The aqueous phase was separated, diluted with water and mixed with toluene. The pH was adjusted to 6 with 25% aqueous sodium hydroxide and the phases separated. The aqueous phase was extracted again with toluene, ensuring a pH=6. The combined organic layers were concentrated in vacuo to yield 51 g of crude racemic N-propargyl-1-aminoindan as a yellow oil. to 45° C. for 4 hours the phases were separated To the organic phase water (64 mL) was added The aqueous phase was separated diluted with water mixed with toluene the phases separated The aqueous phase was extracted again with toluene The combined organic layers were concentrated in vacuo

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

实验步骤: U.S. Pat. No. 5,532,415 discloses process for preparation of R(+)-Rasagiline mesylate which comprises treating a solution of propargyl benzenesulfonate (3) and racemic aminoindan (2) in toluene with aqueous solution of 15% sodium hydroxide to get racemic Rasagiline base (4). The obtained crude racemic Rasagiline is treated with L-tartaric acid in isopropanol (IPA) to get di(R-(+)-N-propargyl-1-aminoindan)-L-tartrate (5) which is recrystallized from 1:1 methanol/isopropanol. The obtained tartrate salt is reacted with methanesulphonic acid in isopropanol at reflux to obtain R(+)-Rasagiline mesylate. The disadvantage of this process is that the scheme consists of low atom efficiency and involves several steps to obtain the final product.

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

实验步骤: The procedure for Example 614 was used, substituting 3-butynyl p-toluenesulfonate for propargyl benzenesulfonate and phenol for m-cresol to provide Example 633. 1H NMR (500 MHz, CDCl3) δ 2.02 (t, J=2 Hz, 1H), 2.68 (dt, J=8, 2 Hz, 2H), 4.08 (t, J=8 Hz, 2H), 6.96 (m, 3H), 7.30 (m, 2H). to provide Example 633

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

实验步骤: A mixture of propargyl benzenesulfonate (1.0 g, 5.1 mmol), m-cresol (0.55 mL, 5.1 mmol) and potassium carbonate (1.1 g, 7.65 mmol) in acetone (40 mL) was stirred at about 56 C for about 2 days. The mixture was cooled, filtered and the solvent was carefully distilled off at atmospheric pressure. The residue was purified by flash chromatography on silica gel using diethyl ether/n-pentane (1:9) as eluent to provide Example 614. 1H NMR (500 MHz, CDCl3): □ 2.33 (s, 3H), 2.50 (t, J=3.0 Hz, 1H), 4.66 (d, J=3.0 Hz, 2H), 6.77-6.82 (m, 3H), 7.15-7.21 (m, 1H). The mixture was cooled filtered the solvent was carefully distilled off at atmospheric pressure The residue was purified by flash chromatography on silica gel to provide Example 614

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

实验步骤: A mixture of propargyl benzenesulfonate (1.0 g, 5.1 mmol), m-cresol (0.55 mL, 5.1 mmol) and potassium carbonate (1.1 g, 7.65 mmol) in acetone (40 mL) was stirred at about 56 C for about 2 days. The mixture was cooled, filtered and the solvent was carefully distilled off at atmospheric pressure. The residue was purified by flash chromatography on silica gel using diethyl ether/n-pentane (1:9) as eluent to provide Example 614. 1H NMR (500 MHz, CDCl3): □ 2.33 (s, 3H), 2.50 (t, J=3.0 Hz, 1H), 4.66 (d, J=3.0 Hz, 2H), 6.77-6.82 (m, 3H), 7.15-7.21 (m, 1H). The mixture was cooled filtered the solvent was carefully distilled off at atmospheric pressure The residue was purified by flash chromatography on silica gel to provide Example 614

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

实验步骤: To a mixture of racemic 1-aminoindan (64 g), 15% aqueous sodium hydroxide solution (141 g), water (107 mL) and toluene (192 mL) there was added propargyl benzenesulfonate (94.3 g) during 20 minutes at ambient temperature. The resulting mixture was heater to 45° C. for 4 hours, at which time the pH was confirmed to be >12(45% sodium hydroxide added if necessary) and the phases were separated. To the organic phase water (64 mL) was added and the pH was adjusted to 2 with 33% aqueous sulfuric acid. The aqueous phase was separated, diluted with water and mixed with toluene. The pH was adjusted to 6 with 25% aqueous sodium hydroxide and the phases separated. The aqueous phase was extracted again with toluene, ensuring a pH=6. The combined organic layers were concentrated in vacuo to yield 51 g of crude racemic N-propargyl-1-aminoindan as a yellow oil. to 45° C. for 4 hours the phases were separated To the organic phase water (64 mL) was added The aqueous phase was separated diluted with water mixed with toluene the phases separated The aqueous phase was extracted again with toluene The combined organic layers were concentrated in vacuo

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

实验步骤: U.S. Pat. No. 5,532,415 discloses process for preparation of R(+)-Rasagiline mesylate which comprises treating a solution of propargyl benzenesulfonate (3) and racemic aminoindan (2) in toluene with aqueous solution of 15% sodium hydroxide to get racemic Rasagiline base (4). The obtained crude racemic Rasagiline is treated with L-tartaric acid in isopropanol (IPA) to get di(R-(+)-N-propargyl-1-aminoindan)-L-tartrate (5) which is recrystallized from 1:1 methanol/isopropanol. The obtained tartrate salt is reacted with methanesulphonic acid in isopropanol at reflux to obtain R(+)-Rasagiline mesylate. The disadvantage of this process is that the scheme consists of low atom efficiency and involves several steps to obtain the final product.