Name: 161735-79-1|(R)-N-(Prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine methanesulfonate|97%
Brand: Ambeed
SKU: A262921
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Yield	Reaction Conditions	Operation in experiment
		6.B.c R-(+)-N-propargyl-1-aminoindan mesylate c) A solution of di-(R-(+)-N-propargyl-1-aminoindan) tartrate (15 g) and methanesulfonic acid (6 g) in isopropanol (150 mL) was heated to reflux for 30 minutes. The reaction was allowed to cool to room temperature and the resulting precipitate isolated by suction filtration to give the titlecompound (11.1 g) with m.p. 157° C. and [α]D =22°.

2
[ 75-75-2 ]
[ 136236-51-6 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	In isopropyl alcohol; for 1h;Reflux;	A suspension of (R)-N-propargyl-1-aminoindan (R-6) (50 mg,0.29 mmol) in 5 mL of isopropanol and 3 L of methanesulfonic acidwas heated to reflux for 1 h. After, the mixture was allowed to coolto 5C. The obtained suspension was filtered, and the collected solidwas washed with 1.5 mL of isopropanol, affording the correspond-ing optically active (R)-<strong>[136236-51-6]rasagiline</strong> mesylate (R-7) as a white solid in98% yield.
86.2%	In toluene; acetonitrile; at 40 - 80℃;Product distribution / selectivity;	Step (b): Preparation of Rasagiline Mesylate The toluenic phase of step (a) was charged into a 500 mL round-bottomed flask under nitrogen and equipped with mechanical stirring. 110 mL of acetonitrile were then added, followed by the dropwise addition of 32.54 g of methanesulfonic acid in about 20 minutes, maintaining the temperature below 40 C. Precipitation started after the addition of approximately 10% of the total amount of methanesulfonic acid. The thick suspension thus obtained was heated up to 75-80 C. and stirred for 30 min. The suspension was then cooled down to 10-15 C., stirred for at least 1 hour and filtered. The collected solid was washed with 3*20 mL of acetonitrile to yield 74.27 g of yellowish wet product (70.95 g of dry crude, partial yield: 86.20%; 99.32% by HPLC).
83%	In isopropyl alcohol; at 5 - 10℃; for 0.5h;	Example 4 Preparation of <strong>[136236-51-6](1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine</strong> mesylate (Rasagiline mesylate) Rasagiline base (81 g, 0.47 moles) was dissolved in IPA (810 ml) under stirring and the obtained solution was cooled to 5C. A solution of methanesulfonic acid (0.49 moles, 47.7 g) in IPA (95 ml) was added dropwise to the above cooled solution. After complete addition, the mixture was stirred for 30 min at 5-10C to get the solid which was filtered and dried to get (105 g, 83%) of Rasagiline mesylate.

83%	In isopropyl alcohol; at 5 - 10℃; for 0.5h;	Example 4 Preparation of <strong>[136236-51-6](1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine</strong> mesylate (Rasagiline Mesylate) Rasagiline base (81 g, 0.47 moles) was dissolved in IPA (810 ml) under stirring and the obtained solution was cooled to 5 C. A solution of methanesulfonic acid (0.49 moles, 47.7 g) in IPA (95 ml) was added dropwise to the above cooled solution. After complete addition, the mixture was stirred for 30 min at 5-10 C. to get the solid which was filtered and dried to get (105 g, 83%) of Rasagiline mesylate.
80%	In isopropyl alcohol; at 20 - 75℃; for 16h;	Embodiment 4 Synthesis of Rasagiline Mesylate 6.2 g of <strong>[136236-51-6]rasagiline</strong> was dissolved in 30 mL of isopropanol in a reaction bottle. 3.7 g of methanesulfonic acid was dropped into the reaction bottle. The mixture was heated to a temperature in a range from 70 to 75 C., to completely dissolve the solids. Then, the mixture was slowly cool down to precipitate solids. The mixture was stirred at room temperature for 16 hours, and then filtered. The filtered solid was washed with isopropanol, and dried, so as to obtain 7.7 g of <strong>[136236-51-6]rasagiline</strong> mesylate. The yield was 80%. 1H NMR data and X-ray diffraction data of the product were shown as follows. 1H NMR (CDCl3):
76.6%	In isopropyl alcohol; at 55 - 80℃; for 1h;	Example 12 Preparation of <strong>[136236-51-6]rasagiline</strong> mesylate 3.23 g of the oily product obtained according to Example 11 were mixed with 22 ml of 2-propanol and the mixture was heated to 80 C. At this temperature methanesulfonic acid (MSA, 1.47 g) was added slowly to the batch. The resulting mixture was cooled to 60C and seeded with 1% of seeding crystals and stirred at a temperature of 55C for 60 minutes. Then the suspension was cooled with the cooling at a rate of 0.5C/min to a temperature of 10C. The mixture was stirred at this temperature for 1 hour, then the product was filtered and washed with 3 ml of 2-propanol. The product was dried and 2.90 g of crystalline product was obtained (assay 99.93%, molar yield 76.6%, enatiomeric purity 100.00 area %, chromatographic purity 100.00%) .
59.4%	In isopropyl alcohol; at 70 - 75℃; for 1h;	Under nitrogen protection, <strong>[136236-51-6]rasagiline</strong> intermediate II 20.0 g (0.108 mol, HPLC purity 96.76%) was added to 100 mL of toluene.Add triphenylsilane with stirring70.3g (0.270mol),Di-o-chlorophenylboric acid1.36 g (0.00542 mol), stirred at 10-15 C for 24 hours.The solvent is removed by vacuum concentration (temperature is preferably 45 C to 65 C, vacuum pressure is preferably -0.085 MPa to -0.1 MPa), and a mass concentration of 10% aqueous sodium hydrogencarbonate solution is added (the mass concentration means that the mass of sodium hydrogencarbonate accounts for carbonic acid). The percentage of the total mass of the aqueous sodium hydrogen solution was quenched and then extracted with dichloromethane.The organic phase is combined, and a mass concentration of 12% hydrochloric acid aqueous solution (the mass concentration refers to the mass of hydrogen chloride as a percentage of the total mass of the hydrochloric acid aqueous solution) is added three times, and the aqueous phase is combined, and the mass concentration is 20% sodium hydroxide aqueous solution. The mass concentration referred to means the mass of sodium hydroxide as a percentage of the total mass of the aqueous sodium hydroxide solution) adjusted to a pH of 10 to 12, followed by extraction with dichloromethane.The organic phase is combined, the mass concentration is 10% aqueous solution of sodium hydrogencarbonate (the mass concentration refers to the mass of sodium hydrogencarbonate as a percentage of the total mass of the aqueous solution of sodium hydrogencarbonate) and the mass concentration is 15% of the brine (the mass concentration) It refers to the washing of sodium chloride as a percentage of the total mass of the brine solution. It is dried over anhydrous sodium sulfate.Filtration, washing and concentration through a funnel padded with 100 g of silica gel to give a pale yellow liquid, dissolved in isopropanol, and added 10.4 g (0.108 mol) of methanesulfonic acid, followed by heating.Stir at 70 to 75 C for 1 hour.Cool to 15 ~ 25 C for 2 hours, filter, cold isopropanol wash, vacuum drying (temperature 45 C ~ 55 C, pressure -0.01MPa ~ -0.1MPa) 12-16 hours to obtain a white solid as methanesulfonic acid Rasagiline I, 17.1g, yield 59.4% (total yield 58.0%, based on (R)-(-)-1-aminoindole), HPLC purity 99.87%, maximum singleAn impurity of 0.04%.
47%	In isopropyl alcohol; for 0.5h;	Rasagiline (1) (1 equivalent) was dissolved in IPA (3 vol) and cooled to 0-50C before a solution of methanesulfonic acid (1 equivalent) in IPA (2 vol) was added. The mixture was stirred for 30 minutes, filtered and the resultant solid washed with IPA (2 vol) and then with TBME (2 vol). The solid was dried under vacuum at lOmbar at 400C to obtain the product as a white solid.Molar yield = 47% Chemical purity = 99.84% (measured by HPLC)Optical purity = 100% (measured by chiral HPLC) (no (S)-enantiomer detected)
	In isopropyl alcohol; for 0.166667h;	The residue after evaporation (<strong>[136236-51-6]rasagiline</strong> base) was dissolved in 214.5 g of isopropanol and 20.4 g of methanesulfonic acid were added over 10 minutes while stirring and cooling. During the addition crystallization of <strong>[136236-51-6]rasagiline</strong> mesylate took place. The resulting suspension was heated while stirring to reflux, and after complete dissolution of solids, was cooled to 10 C. Upon cooling, <strong>[136236-51-6]rasagiline</strong> mesylate was crystallized. The mixture was stirred at 10 C. for 15 minutes and filtered. Solid product was washed on a filter with fresh isopropanol and dried under vacuum at 60 C. 41.0 g of dry <strong>[136236-51-6]rasagiline</strong> mesylate were obtained.
	In methanol; ethyl acetate; at 45℃; for 0.25h;Reflux;	Example 2; Rasagiline base (10 g) was added to a mixture of ethyl acetate (300 ml) and methanol (13 ml), and the mixture was heated to 45-500C. The resulting mass was followed by the addition of methane sulfonic acid (5.89 g) and the mass temperature was raised to reflux. Methanol (32 ml) was added to the resulting mass to provide a clear solution, followed by stirring for 15 minutes. The reaction mass was slowly cooled to 600C without stirring and kept for 1 hour at 600C. The resulting mass was further cooled to 50-550C and kept for 12 hours at 50-550C. The resulting mass was further cooled to 40-450C and maintained for 1-2 hours at 40-450C. The resulting mass was finally cooled to room temperature (25-300C) and maintained for 2 hours. The resulting solid was filtered and then dried at 60 - 65C to produce 9.7 g of <strong>[136236-51-6]rasagiline</strong> mesylate [Purity by HPLC: 99.95%; Particle size Data: (Dgo)^ 1496 microns; (D50)= 864 microns].Level of organic volatile impurities: methanol - 15 parts per million (ppm), isopropyl alcohol - 265 ppm, and toluene - 18 ppm.
	In isopropyl alcohol; at 0 - 5℃;	The <strong>[136236-51-6]rasagiline</strong> base (1 eq) prepared above was taken in isopropyl alcohol (3 vol). The mixture was cooled to 0-5C. To this was added, dropwise, a solution of methanesulfonic acid (1 eq) in isopropyl alcohol (2 vol) at 0-5C and stirred for 1 hour. A white solid crystallised which was filtered and washed with isopropyl alcohol (1 vol). The crystalline <strong>[136236-51-6]rasagiline</strong> mesylate formed was dried under vacuum at 40C for 3 hours.
	In isopropyl alcohol; at 75℃;Product distribution / selectivity;	Rasagiline tartrate (200 g), is charged into a round bottom flask containing water and stirred to produce a solution, and pH is adjusted to 1 1 .98 with aqueous sodium hydroxide solution under constant stirring. Rasagiline free base is extracted from the aqueous solution using two lots of ethyl acetate (930 mL and 1000 mL). The combined organic layer is washed with two lots of water (1070 mL and 1090 mL), followed by distillation under vacuum below 700C. To the residue, ethyl acetate (200 ml) is added and distilled under vacuum to obtain a residue, which is analyzed by chromatography (R-isomer: 98.46%; S-isomer: 1.54%; chemical purity: 99.28%). The residue is dissolved in isopropyl alcohol (1200 mL), followed by addition of methanesulfonic acid (93.7 g) over 15 minutes. The mixture is stirred and heated to 75C under constant stirring and maintained at that temperature for 10 minutes. The mixture is allowed to cool to 25C, and then precipitated solid is filtered and washed with isopropyl alcohol (200 mL). The filtered solid is suction dried, then dried at 700C for about 8 hours to give <strong>[136236-51-6]rasagiline</strong> mesylate in 83% yield.Chiral purity: R-Propargylaminoindane mesylate = 99.95%; S-Propargyl aminoindane mesylate = 0.05%.Chemical purity: Rasagiline mesylate >99.9%; N-Allylaminoindane <0.05%.
		3. Salt formationCrude <strong>[136236-51-6]rasagiline</strong> base from the hydrolysis step was dissolved in i-PrOH (75 mL), filtered and heated to 50-60 C. MsOH (8.04 g, 83.6 mmol, 1.0 eq.) was added dropwise in 5-10 min, seeded with Rasagiline mesylate crystal resulting in a fast crystallization of the product. Solution was further stirred for 15 min at this temperature after which the solution was cooled down to room temperature, filtered and washed with cold IPA to obtain 20.5 g Rasagiline mesylate as white crystals in 88% overall yield starting from Formula 3 and 100% purity (by HPLC).
	In acetone; at 25 - 35℃; for 1h;	ExampIe-7:Preparation of (R)-<strong>[136236-51-6]rasagiline</strong> Mesylate Form-I3.4 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 27 mL acetone were taken in round bottom flask at 25C. 8.7 g of methane sulphonic acid was added and maintain for 1 hour at 35C. The reaction mixture was filtered and wet-cake was washed with acetone and dried for 12 hours at 55C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> Mesylate. The product is characterized by XRD (FIG.11) and IR (FIG.12). The water content is less than 0.5%, which shows it is anhydrous.
17.8 g	In isopropyl alcohol; at 25 - 65℃; for 0.5h;	Example-2-Preparation of R(+) N propargyl amino indane Mesylate A solution of methanesulfonic acid (13.50g) in Isopropyl alcohol (100.00ml) was added drop wise to a solution of Pure Rasagiline free base (20.00g) in Isopropyl alcohol (100.00ml) at 25-27 deg C. The temperature was then raised to 35-38 deg C and the reaction mixture was heated to 60-65 deg C for 30 minutes to provide a clear solution. The hot bath was removed and the reaction mass was allowed to come to 28-30 deg C.The reaction mass was cooled to 10 +/-2 deg C and the mass maintained for 1 hr. The mass was filtered under suction, the bed washed with chilled (-2 to 0 deg C) Isopropyl alcohol and dried in oven at 85-90 deg C. Yield 17.8g Purity: 99.99 %.
	In isopropyl alcohol; at 50 - 60℃;	Crude <strong>[136236-51-6]rasagiline</strong> base from the hydrolysis step was dissolved in i-PrOH (75 mL), filtered and heated to 50-60 C. MsOH (8.04 g, 83.6 mmol, 1.0 eq.) was added dropwise in 5-10 min, seeded with Rasagiline mesylate crystal resulting in a fast crystallization of the product. Solution was further stirred for 15 min at this temperature after which the solution was cooled down to room temperature, filtered and washed with cold IPA to obtain 20.5 g Rasagiline mesylate as white crystals in 88% overall yield starting from Formula 3 and 100% purity (by HPLC).

Reference： [1]Applied Catalysis A: General,2015,vol. 492,p. 76 - 82
[2]Patent: US2009/292141,2009,A1 .Location in patent: Page/Page column 4
[3]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 13
[4]Patent: US8741962,2014,B2 .Location in patent: Page/Page column 17
[5]Organic Process Research and Development,2014,vol. 18,p. 1169 - 1174
[6]Patent: US2011/218361,2011,A1 .Location in patent: Page/Page column 4-5
[7]Patent: WO2015/70995,2015,A1 .Location in patent: Page/Page column 27
[8]Patent: CN109180499,2019,A .Location in patent: Paragraph 0073-0079; 0080-0085
[9]Patent: WO2009/147432,2009,A1 .Location in patent: Page/Page column 14
[10]Patent: US2007/112217,2007,A1 .Location in patent: Page/Page column 13
[11]Patent: WO2009/122301,2009,A2 .Location in patent: Page/Page column 12
[12]Patent: WO2010/13048,2010,A1 .Location in patent: Page/Page column 10
[13]Patent: WO2010/59913,2010,A2 .Location in patent: Page/Page column 23-24
[14]Patent: WO2012/96635,2012,A1 .Location in patent: Page/Page column 7
[15]Patent: WO2012/153349,2012,A2 .Location in patent: Page/Page column 29
[16]Patent: WO2013/54346,2013,A2 .Location in patent: Page/Page column 13
[17]Patent: US2014/18578,2014,A1 .Location in patent: Paragraph 0031

3
[ 161735-79-1 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
91.6%	With sodium hydroxide; In water; at 3 - 5℃; for 1h;pH 7.5 - 11;Product distribution / selectivity;	15 g of rasagiline mesylate were dissolved in 150 ml water while stirring. The solution was cooled to 5 C. and 25% NaOH solution was added slowly. During the addition, batch temperature was maintained between 3 and 5 C. Solid precipitation was observed after reaching a pH of 7.5. After reaching a pH of 11, the NaOH addition was stopped, the batch was stirred while cooling for one hour and filtered. The filtration proceeded quickly. The solid product was washed with water on the filter and dried under vacuum.8.8 g of solid dried rasagiline base were attained. The yield was 91.6%. The melting point of the solid was determined to be 38.2-38.4 C.
91.6%	With sodium hydroxide; In water; at 3 - 5℃;pH 11;	EXAMPLE 3; Splitting and Spontaneous Crystallization from Water15 g of rasagiline mesylate were dissolved in 150 ml water while stirring. The solution was cooled to 5 C. and 25% NaOH solution was added slowly. During the addition, batch temperature was maintained between 3 and 5 C. Solid precipitation was observed after reaching a pH of 7.5. After reaching a pH of 11, the NaOH addition was stopped, the batch was stirred while cooling for one hour and filtered. The filtration proceeded quickly. The solid product was washed with water on the filter and dried under vacuum.8.8 g of solid dried rasagiline base were attained. The yield was 91.6%. The melting point of the solid was determined to be 38.2-38.4 C.
	With sodium hydroxide; In water; toluene;pH ~ 14;	120 g of rasagiline mesylate (R(+)-N-propargyl-1-aminoindan mesylate) were dissolved in 700 ml of deionized water. 400 ml of toluene were added and the mixture was basified with 25% NaOH solution to a pH of about 14. After stirring, two phases separated. The lower water phase was extracted with 200 ml of toluene. The phases were allowed to separate and the aqueous phase was discarded.The two toluenic extractions were combined and the solvent was distilled under vacuum. The yield of rasagiline base was 88.5 g of a yellowish oil with a melting point of below 20 C.; B) Crystallization of Rasagiline Base148 g of rasagiline base oil prepared as described above were dissolved in 180 ml of isopropanol. The solution was cooled to 17 C. and 252 ml of deionized water were added at this temperature. The solution was cooled to 10 C. and seeded with solid rasagiline base. Immediate crystallization was observed. 100 ml of water were then added to the mixture. The mixture was cooled to 1 C., stirred at this temperature for 30 min and filtered. The solid was washed on the filter with 200 ml of water and dried under vacuum.

With sodium hydroxide; In water; toluene;pH 14;

120 g of rasagiline mesylate were dissolved in 700 ml of deionized water. 400 ml of toluene were added and the mixture was basified with 25% NaOH solution to a pH of about 14. After stirring, two phases separated. The lower water phase was extracted with 200 ml of toluene. The phases were allowed to separate and the aqueous phase was discarded.The two toluenic extractions were combined and the solvent was distilled under vacuum. The yield of rasagiline base was 88.5 g of a yellowish oil with a melting point of below 20 C.25.1 g of the liquid rasagiline base was sampled. The sample was mixed with ethanol and the solvent was distilled under vacuum. 22.6 g of the rasagiline base residue, in the form of a yellowish oil remained after the ethanol evaporation. The rasagiline base in oil form remained in oil form for a number of weeks, and did not crystallize spontaneously.

Reference： [1]Patent: US2008/161408,2008,A1 .Location in patent: Page/Page column 3
[2]Patent: US2009/318564,2009,A1 .Location in patent: Page/Page column 4
[3]Patent: US2008/146676,2008,A1 .Location in patent: Page/Page column 1-2
[4]Patent: US2008/161408,2008,A1 .Location in patent: Page/Page column 2; 3

4
(R-(+)-N-propargyl-1-aminoindan)L-tartarate [ No CAS ]
[ 161735-79-1 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; toluene; at 40 - 50℃;pH 14;Product distribution / selectivity;	155 g of rasagiline tartrate, prepared essentially as described in U.S. Pat. No. 5,532,415 example 6B, and 20 g of rasagiline mesylate, prepared as described in example 1, were dissolved in 800 ml of water. 400 ml of toluene were added to the solution and the mixture was basified with 25% NaOH solution to a pH of about 14 and heated to 45+/-5 C.After stirring, two phases were separated. The lower water phase was extracted twice with 300 ml of toluene at 45+/-5 C. The organic phases were combined and the aqueous phase was discarded.The combined organic phase was washed with 200 ml of deionized water. Then the solvent was distilled under vacuum and 50 ml isopropanol were added to the resulting residue. The solvent was removed by vacuum and additional 50 ml isopropanol were added and then removed by vacuum. 100 g of syrup-like liquid rasagiline base were formed.

Reference： [1]Patent: US2008/161408,2008,A1 .Location in patent: Page/Page column 3

5
[ 75-75-2 ]
[ 1166392-46-6 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-(2,3 dibromopropyl)-1-aminoindan With potassium hydroxide In denaturated industrial spirit; water at 80 - 90℃; for 5h; Stage #2: methanesulfonic acid In isopropyl alcohol at 25 - 30℃;	8 N-(2,3 dibromo propyl)-i-aminoindan (lisgm) was dissolved in 500 ml denatured industrial spirit, 100ml water was added followed by 100 gm potassium hydroxide. The mixture was heated to 80-90 C for 5 hrs. The reaction mass was quenched into 2.5 lit water and extracted with 250 ml ethyl acetate. The organic phase was dried & concentrated to residue. The residue was dissolved in isopropyl alcohol (160ml) at 25-30C. L-tartaric acid (i3.5gm) dissolved in (20 ml ) of water was added at 25-30 C and the reaction mass was heated at 600C for 30 min. and cooled to 25-30 C under stirring. The resulting suspension was filtered. This solid was refluxed under stiiring in a mixture of methanol : isopropyl alcohol 1 :i (300ml). The slurry was cooled at o- 5 0C and filtered.This solid was further stirred with 10% sodium hydroxide solution and extracted with dichloro methane 250ml. The organic layer was separated, dried and concentrated under vacuum to residue. The residue is dissolved in isopropyl alcohol and 5.7 ml methane sulphonic acid was added dropwise at 25-30 C. The resulting suspension was cooled to 0-5 0C and filtered. The solid was further recrystallised from isopropyl alcohol to get 10 gms (R) N-propargyl l-indanamine mesylate HPLC (99.8%) Chiral purity (99.5%).

Reference： [1]Current Patent Assignee: CIPLA LTD - WO2009/81148, 2009, A1 Location in patent: Page/Page column 12-13

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20 - 25℃;	1 Examples 1-13: Preparation of Rasagiline mesylate form I. General procedure: rasagiline mesylate (100 mg) was suspended in a solvent (1 mL) and heated (in a closed vial) at the temperature indicated in the table for 1 hour. The mixtures were allowed to cool to ambient temperature, stirred for 24 hours at this temperature before evaporation of the solvent (by opening the vial and allowing to evaporate under ambient temperature pressure conditions). The results are summarized in Table 1.
	In methanol; ethyl acetate for 0.25h; Reflux;	1 EXAMPLES; Example 1; Rasagiline mesylate (5 g) was added to ethyl acetate (150 ml) and the mixture was heated to reflux, followed by the addition of methanol (20 ml), to form a clear solution, and then stirred for 15 minutes. The resulting solution was slowly cooled to 6O0C with slow stirring. The stirring was stopped and the reaction mass was maintained for 1 hour at same temperature to grow the crystals. The resulting mass was further cooled to 45-500C and kept for 12 hours at 45-500C. The resulting mass was finally cooled to 25-300C, the material was filtered and then dried under vacuum at 60 - 65°C to produce 3.7 g of rasagiline mesylate [Purity by HPLC: 99.92%; Particle size Data: (D90) = 1407 microns; (D50) = 663 microns].Level of organic volatile impurities: methanol - 10 parts per million (ppm), isopropyl alcohol - 294 ppm, and toluene - 17 ppm.
	In acetonitrile at 0℃; Reflux;	3.c Step (c): Purification of Rasagiline Mesylate The wet crude obtained in step (b) was charged into a 500 mL round-bottomed flask together with 426 mL of acetonitrile. The suspension was heated up to reflux until complete dissolution occurred, cooled down to 20-25° C. and stirred for 1 hour, cooled down further to 0-5° C. and stirred for at least 1 hour more. The suspension was then filtered, and the collected solid was washed with 2*55 mL of acetonitrile to give 67.38 g of white wet product (65.76 g of dry crude, partial yield 92.68%; 99.93% by HPLC).

	In isopropyl alcohol at -20 - 75℃;	3 Example 3; Preparation of (R)-N-propargyl-1-aminoindane MesylateBy proceeding according to Example 2, the isopropanol solution of Rasagiline mesylate, which is obtained after decoloration by adding carbon, is quickly cooled for example in about 30 minutes, at about 0° C. and 10° C., to obtain a precipitate of Rasagiline mesylate. Subsequently the crystalline dispersion is heated for about 15-30 minutes, to about 70-75° C., to almost complete redissolution of the precipitate and finally cooled to about -20° C. and 40° C., more preferably to about 0° C. and 10° C., to obtain a precipitate of crystalline Rasagiline mesylate. The product has a DSC thermogram as reported in FIG. 2 and a XRPD spectrum as illustrated in FIG. 1, wherein the most intense diffraction peaks fall at 4.6; 9.1; 13.7; 16.4; 16.8; 18.3; 21.2; 21.7; 22.3; 22.9; 24.4; 26.2; e 27.5+/-0.2° in 2θ.
	In acetonitrile at 25 - 55℃;	1 Example 1; Rasagiline mesylate (1 eq) was taken in acetonitrile (4 vol) and heated to 55°C for 20-30 minutes until a clear solution was obtained. The solution was cooled to 25°C for 30 minutes and filtered. The solid product was dried at 25-30°C under vacuum for 2 hours. XRPD and DSC analysis data confirmed that the product obtained was a crystalline form of rasagiline mesylate.
	In isopropyl alcohol Reflux;	69 Example 69; Preparation of Rasagiline Mesylate9.04 g of rasagiline mesylate and 36 mL of isopropanol were heated to reflux, until complete dissolution occurred, and stirred for 30 minutes at reflux. After this time, the mixture was cooled down to 0-5° C. and stirred for 30 minutes. The suspension was then filtered, and the collected solid was washed with 10 mL of isopropanol and dried at 50° C. for 4 h under vacuum. 8.66 g of white solid were thus obtained (95.80% yield).
	In isopropyl alcohol at 0 - 5℃; for 1h; Reflux;	1 Reference Example 1; Preparation of Rasagiline Mesylate Crystals9.04 g of rasagiline mesylate and 36 mL of isopropanol were heated to reflux, until complete dissolution occurred, and stirred for 30 minutes at reflux. After this time, the mixture was cooled down to 0-5° C. and stirred for 30 minutes. The suspension was then filtered, and the collected solid was washed with 10 mL of isopropanol and dried at 50° C. for 4 h under vacuum. 8.66 g of white solid were thus obtained (95.80% yield).Analytical data: Particle size: D(v, 0.1): 17.4 μm, D(v, 0.5): 62.6 μm, D(v, 0.9): 118.0 μm.; Bulk density (g/mL): 0.236; Tapped density (g/mL): 0.407; HR: 1.72; CI: 42; Specific Surface Area (BET): 0.3216 m2/g.
	In dichloromethane at 25℃; for 1h;	1 Examples 1-13; Preparation of Rasagiline Mesylate form IGeneral procedure: rasagiline mesylate (100 mg) was suspended in a solvent (1 mL) and heated (in a closed vial) at the temperature indicated in the table for 1 hour. The mixtures were allowed to cool to ambient temperature, stirred for 24 hours at this temperature before evaporation of the solvent (by opening the vial and allowing to evaporate under ambient temperature pressure conditions). The results are summarized in Table 1.
	In isopropyl alcohol at 20 - 65℃;	2 Example-2; Rasagiline mesylate (462.0 g) was added to isopropyl alcohol (4620 ml) taken in a R.B.F.The reaction mass was heated to 60-65"C under stirring. The reaction mixture was maintained at the same temperature until a clear solution was obtained.Heating and stirring were stopped and the reaction mixture gradually cooled to room temperature in around 15 hours. The reaction mass was filtered under vacuum and dried under vacuum (650-750 mm Hg) at 60-65 °C for around 12 hoursDry wt =367 g. Yield=79.44%. Purity = 99.3% Particle size data (D90) = 337. 1 μm.
	In methanol at 20℃; Distillation;	24 Rasagiline mesylate (1.0 g) is charged into a flask containing methanol (4 mL). The solvent is distilled under vacuum below 20° C. A vacuum is applied after distillation for about 2-3 hours.

7
[ 75-75-2 ]
(1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine L-(+)-tartrate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: (1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine L-(+)-tartrate With sodium hydrogencarbonate In water; ethyl acetate at 20 - 25℃; Inert atmosphere; Stage #2: methanesulfonic acid In isopropyl alcohol Reflux;	2 Example 2; Preparation of (R)-N-propargyl-1-aminoindane MesylateIn a IL rector maintained under nitrogen atmosphere, N-propargyl-1-aminoindane (47.43 g; 277 mmol) obtained from Example 1, ethanol (340 mL) and L(+)-tartaric acid (21.2 g; 141.25 mmol) are added. The mixture is refluxed for about 1 h. Then the mixture is cooled at 0-5° C., in 5-6 h, and kept to such temperature for about 1 h. The mixture is filtered and the filter washed with 0-5° C. pre-cooled ethanol. 48 g of wet solid are obtained which are dried in oven at 60° C. to constant weight. 31.6 g of (R)-N-propargyl-1-aminoindane tartrate are obtained.(R) -N-propargyl-1-aminoindane tartrate (31.6 g; 128.46 mmol), thus obtained, is loaded in a 1 L reactor and maintained under nitrogen atmosphere. Ethyl acetate (217 mL), sodium bicarbonate (13.5 g; 160.71 mmol) and water (190 mL) are added. The mixture is stirred to complete dissolution at 20-25° C. The phases are separated and the organic one is washed with water (30 mL). The phases are separated again and the organic one is concentrated under vacuum, obtaining (R)-N-propargyl-1-aminoindane as an oily residue. The residue is taken up with isopropanol (50 mL) and the solvent distilled off under vacuum to dryness. The residue is then cooled at 40-50° C. and taken up with isopropanol (65 mL). Metansulphonic acid (11.5 g; 119.66 mmol) is added to the solution. The mixture is heated to reflux to obtain a solution which is discoloured by adding carbon. The clear solution is cooled at 75° C., and left to crystallize. The solution is cooled at 0-5° C. in 5-6 h and maintained at such temperature for at least 1 h. 32 g of wet solid are recovered by filtration, the solid is dried in oven at 60° C. to constant weight. 28.7 g of (R)-N-propargyl-1-aminoindane mesylate are obtained. Yield: 89% from (R)-N-propargyl-1-aminoindane tartrate. The product has a DSC thermogram as reported in FIG. 2, and a XRPD spectrum as illustrated in FIG. 1, wherein the most intense diffraction peaks fall at 4.6; 9.1; 13.7; 16.4; 16.8; 18.3; 21.2; 21.7; 22.3; 22.9; 24.4; 26.2; and 27.5+/-0.2° in 2θ.

Reference： [1]Current Patent Assignee: DIPHARMA FRANCIS S.R.L. - US2010/29987, 2010, A1 Location in patent: Page/Page column 4

8
[ 75-75-2 ]
(R-(+)-N-propargyl-1-aminoindan)L-tartarate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
100 % ee	In acetone for 0.75h; Reflux;	14 A rasagiline tartrate salt (25 g) is charged into a round-bottom flask containing acetone (375 mL) and stirred for about 5 minutes. Methanesulfonic acid (11.22 g) is added to the solution, heated to reflux, and maintained for about 45 minutes. The solution is cooled to 25-30°C and stirred for solid formation. The solid is filtered, washed with acetone (50 mL), and dried under vaccum at 600C to afford the title compound (19 g).Purity by chiral HPLC: 100% R-isomer.

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2010/59913, 2010, A2 Location in patent: Page/Page column 21

9
[ 34698-41-4 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium carbonate / acetonitrile / 24 h / 55 °C 2.1: isopropyl alcohol / 1.5 h / 25 - 30 °C / Reflux 3.1: ammonia / water / pH ~ 8.5 - 9 3.2: 2 h / 25 - 30 °C
	Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 2: 0.75 h / 25 - 65 °C 3: sodium hydroxide / water / 20 °C 4: acetone / 1 h / 25 - 35 °C
	Multi-step reaction with 5 steps 1.1: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 2.1: 0.75 h / 25 - 65 °C 3.1: sodium hydroxide / water / 20 °C 4.1: hydrogen bromide / 0.5 h / 25 - 65 °C 5.1: sodium hydroxide / ethyl acetate / 4 h / 65 °C 5.2: 0.5 h / 40 °C

	Multi-step reaction with 4 steps 1: Candida antarctica lipase B; Pd/AlO(OH); potassium carbonate / toluene / 12 h / 50 °C / Resolution of racemate; Inert atmosphere; Schlenk technique; Enzymatic reaction 2: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 3: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 4: isopropyl alcohol / 0.5 h / 5 - 10 °C
	Multi-step reaction with 6 steps 1: ethanol; tert-butyl methyl ether / 20 °C 2: ethanol / 2.32 h / 79 °C 3: sodium hydroxide / ethyl acetate / 0.5 h / 20 °C 4: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 5: sodium hydroxide / toluene / 29 h / 30 °C 6: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2011/48612, 2011, A2
[2]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[3]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[4]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]
[5]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

10
[ 75-75-2 ]
[ 1201685-18-8 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine L-(+)-tartrate With ammonia In water Stage #2: methanesulfonic acid In acetone at 25 - 30℃; for 2h;	3 EXAMPLE 3 : PREPARATION OF R-(+)-RASAGILINE MESYLATE. R-(+) Rasagi l ine tartrate ( 20.0g, 0.081 mol) was dissolved in DM water (200 ml) and the pH of the solution was adj usted to about 8.5-9 by adding aqueous ammonia solution. The solution was extracted with cyclohexane and the organic layer was concentrated at about 40- 45°C to obtain a oily residue (9 gm)(assay by HPLC 97.35%). The residue was dissolved in acetone at about 25-3.0º C and stirred with methane sulfonic acid (6.06 g, 1 .20 mol) at 25- 30°C for 2h The prec ipitated. Rasagiline mesylate was filtered and dried at about 50-55°C to obtain 12 gm of Rasagi li ne mesylate.Purity by HPLC : 99.97 %.Particle size distri bution : D m - 1 6.79μιη; D50 = 39.1 8μηι D90 = 74.327 μm.

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2011/48612, 2011, A2 Location in patent: Page/Page column 23

11
[ 83-33-0 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: ethanol / 8 h / 25 - 30 °C 2.1: ethanol; sodium tetrahydroborate / 8 h / 25 - 30 °C 3.1: isopropyl alcohol / 1.5 h / 25 - 30 °C / Reflux 4.1: ammonia / water / pH ~ 8.5 - 9 4.2: 2 h / 25 - 30 °C
	Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / tert-butyl methyl ether / 8 h 1.2: 1 h / -70 - -30 °C 2.1: diisobutylaluminium hydride / toluene; hexane / 1 h / -70 - -30 °C 2.2: 1 h / 20 °C 3.1: tert-butyl methyl ether / 21 h / 10 °C / Heating 4.1: sodium hydroxide 5.1: isopropyl alcohol / 16 h / 20 - 75 °C
	Multi-step reaction with 6 steps 1: hydroxylamine hydrochloride; sodium hydroxide / water; methanol / 70 - 75 °C 2: hydrogen; ammonia / Raney nickel / methanol / 10 - 42 °C / Autoclave 3: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 4: 0.75 h / 25 - 65 °C 5: sodium hydroxide / water / 20 °C 6: acetone / 1 h / 25 - 35 °C

	Multi-step reaction with 7 steps 1.1: hydroxylamine hydrochloride; sodium hydroxide / water; methanol / 70 - 75 °C 2.1: hydrogen; ammonia / Raney nickel / methanol / 10 - 42 °C / Autoclave 3.1: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 4.1: 0.75 h / 25 - 65 °C 5.1: sodium hydroxide / water / 20 °C 6.1: hydrogen bromide / 0.5 h / 25 - 65 °C 7.1: sodium hydroxide / ethyl acetate / 4 h / 65 °C 7.2: 0.5 h / 40 °C
	Multi-step reaction with 6 steps 1: hydroxylamine hydrochloride / ethanol; water / 0.75 h / Reflux 2: palladium 10% on activated carbon; hydrogen / ethanol / 4 h / 70 °C 3: Candida antarctica lipase B; Pd/AlO(OH); potassium carbonate / toluene / 12 h / 50 °C / Resolution of racemate; Inert atmosphere; Schlenk technique; Enzymatic reaction 4: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 5: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 6: isopropyl alcohol / 0.5 h / 5 - 10 °C
	Multi-step reaction with 6 steps 1: sodium tetrahydroborate / methanol / 3 h / 0 - 20 °C 2: Thermomyces lanuginosus lipase / hexane / 0.25 h / 35 °C / Inert atmosphere; Resolution of racemate; Enzymatic reaction 3: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 4: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 5: potassium carbonate / acetonitrile / 16 h / 60 °C 6: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 6 steps 1: sodium tetrahydroborate / methanol / 3 h / 0 - 20 °C 2: pseudomonas fluorescens lipase / toluene / 6 h / 30 °C / Inert atmosphere; Resolution of racemate; Enzymatic reaction 3: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 4: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 5: potassium carbonate / acetonitrile / 16 h / 60 °C 6: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 7 steps 1: sodium tetrahydroborate / methanol / 3 h / 0 - 20 °C 2: dmap / dichloromethane / 4 h / 20 °C 3: Candida rugosa lipase / tetrahydrofuran; aq. phosphate buffer / 24 h / 30 °C / pH 7 / Resolution of racemate; Enzymatic reaction 4: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 5: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 6: potassium carbonate / acetonitrile / 16 h / 60 °C 7: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 8 steps 1: hydroxylamine hydrochloride / ethanol / 0.17 h / 20 - 25 °C 2: ammonia; hydrogen / methanol / 20 h / 42 °C / 2625.26 Torr 3: ethanol; tert-butyl methyl ether / 20 °C 4: ethanol / 2.32 h / 79 °C 5: sodium hydroxide / ethyl acetate / 0.5 h / 20 °C 6: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 7: sodium hydroxide / toluene / 29 h / 30 °C 8: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2011/48612, 2011, A2
[2]Current Patent Assignee: EVERLIGHT CHEMICAL INDUSTRIAL CORPORATION - US2011/218361, 2011, A1
[3]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[4]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[5]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]
[6]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[7]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[8]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[9]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

12
C₂₁H₃₃NO₄Ti [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: ethanol; sodium tetrahydroborate / 8 h / 25 - 30 °C 2.1: isopropyl alcohol / 1.5 h / 25 - 30 °C / Reflux 3.1: ammonia / water / pH ~ 8.5 - 9 3.2: 2 h / 25 - 30 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2011/48612, 2011, A2

13
[ 136236-51-6 ]
[ 161735-79-1 ]

Reference： [1]Patent: WO2012/153349,2012,A2

14
[ 1875-50-9 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tert-butyl methyl ether / 21 h / 10 °C / Heating 2: sodium hydroxide 3: isopropyl alcohol / 16 h / 20 - 75 °C
	Multi-step reaction with 3 steps 1: 0.75 h / 25 - 65 °C 2: sodium hydroxide / water / 20 °C 3: acetone / 1 h / 25 - 35 °C
	Multi-step reaction with 4 steps 1.1: 0.75 h / 25 - 65 °C 2.1: sodium hydroxide / water / 20 °C 3.1: hydrogen bromide / 0.5 h / 25 - 65 °C 4.1: sodium hydroxide / ethyl acetate / 4 h / 65 °C 4.2: 0.5 h / 40 °C

Reference： [1]Current Patent Assignee: EVERLIGHT CHEMICAL INDUSTRIAL CORPORATION - US2011/218361, 2011, A1
[2]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[3]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2

15
[ 1227784-59-9 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: diisobutylaluminium hydride / toluene; hexane / 1 h / -70 - -30 °C 1.2: 1 h / 20 °C 2.1: tert-butyl methyl ether / 21 h / 10 °C / Heating 3.1: sodium hydroxide 4.1: isopropyl alcohol / 16 h / 20 - 75 °C

Reference： [1]Current Patent Assignee: EVERLIGHT CHEMICAL INDUSTRIAL CORPORATION - US2011/218361, 2011, A1

16
[ 1309125-23-2 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: isopropyl alcohol / 16 h / 20 - 75 °C

Reference： [1]Current Patent Assignee: EVERLIGHT CHEMICAL INDUSTRIAL CORPORATION - US2011/218361, 2011, A1

17
(R)-2,3-dihydro-1H-inden-1-amine hydrochloride [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide; tetrabutylammomium bromide / water / 0.25 h / 15 - 20 °C 1.2: 2.75 h / 15 - 20 °C 2.1: isopropyl alcohol / 0.5 h / 5 - 10 °C
	Multi-step reaction with 4 steps 1.1: pyridine / dichloromethane / 0.58 h / 20 °C / Ice bath 2.1: caesium carbonate / acetonitrile / 0.17 h / 30 - 35 °C 2.2: 4 h / 30 - 35 °C 3.1: potassium hydroxide / water; methanol / 30 - 35 °C 4.1: isopropyl alcohol / 20 - 60 °C 4.2: 0.42 h / 20 - 60 °C
	Multi-step reaction with 2 steps 1.1: sodium hydroxide; tetrabutylammomium bromide / water / 0.25 h / 15 - 20 °C 1.2: 2.75 h / 15 - 20 °C 2.1: isopropyl alcohol / 0.5 h / 5 - 10 °C

Multi-step reaction with 2 steps 1: sodium hydroxide / toluene / 29 h / 30 °C 2: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: USV PRIVATE - EP2364967, 2011, A2
[2]Current Patent Assignee: NOBEL ILAC SANAYII VE TICARET A.S. - WO2012/96635, 2012, A1
[3]Current Patent Assignee: USV PRIVATE - US8741962, 2014, B2
[4]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

18
[ 75-75-2 ]
rasagiline tartrate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	In isopropyl alcohol at 5℃; for 1.5h; Reflux;	5 Example 5 Preparation of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine mesylate (Rasagiline mesylate) Rasagiline tartrate (15.0 g, 0.046 moles) was added to IPA (150 ml) under stirring followed by addition of methanesulfonic acid (6.0 g, 0.06 moles). The mixture was heated to reflux for 45 min. and cooled to room temperature. The mixture was further cooled to 5-10°C and stirred for 45 min. The obtained solid was filtered and dried to get (18 g, 83%) of the title compound.

Reference： [1]Current Patent Assignee: USV PRIVATE - EP2364967, 2011, A2 Location in patent: Page/Page column 13

19
[ 155666-94-7 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: caesium carbonate / acetonitrile / 0.17 h / 30 - 35 °C 1.2: 4 h / 30 - 35 °C 2.1: potassium hydroxide / water; methanol / 30 - 35 °C 3.1: isopropyl alcohol / 20 - 60 °C 3.2: 0.42 h / 20 - 60 °C
	Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile; toluene / 30 - 35 °C 2: potassium hydroxide; water / methanol / 0.5 h / 30 - 35 °C 3: isopropyl alcohol / 50 - 60 °C

Reference： [1]Current Patent Assignee: NOBEL ILAC SANAYII VE TICARET A.S. - WO2012/96635, 2012, A1
[2]Current Patent Assignee: NOBEL ILAC SANAYII VE TICARET A.S. - US2014/18578, 2014, A1

20
[ 75-75-2 ]
[ 694436-33-4 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine hydrobromide With sodium hydroxide In ethyl acetate at 65℃; for 4h; Stage #2: methanesulfonic acid In ethyl acetate at 40℃; for 0.5h;	6 ExampIe-6:Preparation of (R)-Rasagiline Mesylate15.0 g rasagiline hydrobromide Form-I and 150 ml ethyl acetate were taken in round bottom flask. 10% NaOH 20 g in ethyl acetate was added to the reaction mixture and heated to 65°C. The reaction mixture was stirred for 4 hours at same temperature. After the completion of the reaction, the reaction mixture was distilled to remove ethyl dropwise addition of methanesulfonic acid 6 g and stirred at 40°C for 30 minutes. The reaction was cooled to room temperature and resulting crystals were isolated by suction filtration to give the title compound with m.p. 157°C.

Reference： [1]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2 Location in patent: Page/Page column 28-29

21
indan-1-one oxime [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrogen; ammonia / Raney nickel / methanol / 10 - 42 °C / Autoclave 2: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 3: 0.75 h / 25 - 65 °C 4: sodium hydroxide / water / 20 °C 5: acetone / 1 h / 25 - 35 °C
	Multi-step reaction with 6 steps 1.1: hydrogen; ammonia / Raney nickel / methanol / 10 - 42 °C / Autoclave 2.1: potassium carbonate; N,N-dimethyl-formamide; sodium hydroxide / 7 h / 40 - 70 °C 3.1: 0.75 h / 25 - 65 °C 4.1: sodium hydroxide / water / 20 °C 5.1: hydrogen bromide / 0.5 h / 25 - 65 °C 6.1: sodium hydroxide / ethyl acetate / 4 h / 65 °C 6.2: 0.5 h / 40 °C
	Multi-step reaction with 5 steps 1: palladium 10% on activated carbon; hydrogen / ethanol / 4 h / 70 °C 2: Candida antarctica lipase B; Pd/AlO(OH); potassium carbonate / toluene / 12 h / 50 °C / Resolution of racemate; Inert atmosphere; Schlenk technique; Enzymatic reaction 3: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 4: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 5: isopropyl alcohol / 0.5 h / 5 - 10 °C

Multi-step reaction with 7 steps 1: ammonia; hydrogen / methanol / 20 h / 42 °C / 2625.26 Torr 2: ethanol; tert-butyl methyl ether / 20 °C 3: ethanol / 2.32 h / 79 °C 4: sodium hydroxide / ethyl acetate / 0.5 h / 20 °C 5: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 6: sodium hydroxide / toluene / 29 h / 30 °C 7: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[2]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2
[3]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]
[4]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

22
di-(R-(+)-N-propargyl-1-aminoindan) L-tartrate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 20 °C 2.1: hydrogen bromide / 0.5 h / 25 - 65 °C 3.1: sodium hydroxide / ethyl acetate / 4 h / 65 °C 3.2: 0.5 h / 40 °C

Reference： [1]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/153349, 2012, A2

23
[ 75-75-2 ]
rasagiline tartrate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	In isopropyl alcohol at 5 - 10℃; for 0.75h;	5 Example 5 Preparation of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine mesylate (Rasagiline Mesylate) Example 5 Preparation of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine mesylate (Rasagiline Mesylate) Rasagiline tartrate (15.0 g, 0.046 moles) was added to IPA (150 ml) under stirring followed by addition of methanesulfonic acid (6.0 g, 0.06 moles). The mixture was heated to reflux for 45 min. and cooled to room temperature. The mixture was further cooled to 5-10° C. and stirred for 45 min. The obtained solid was filtered and dried to get (18 g, 83%) of the title compound.

Reference： [1]Current Patent Assignee: USV PRIVATE - US8741962, 2014, B2 Location in patent: Page/Page column 17

24
N-[(1R)-2,3-dihydro-1H-inden-1-yl]-2-methoxyacetamide [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 2: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 3: isopropyl alcohol / 0.5 h / 5 - 10 °C

Reference： [1]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]

25
(S)-1-Aminoindane [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Pd/AlO(OH) / toluene / 6 h / 70 °C / Inert atmosphere; Schlenk technique 2: Candida antarctica lipase B; Pd/AlO(OH); potassium carbonate / toluene / 12 h / 50 °C / Resolution of racemate; Inert atmosphere; Schlenk technique; Enzymatic reaction 3: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 4: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 5: isopropyl alcohol / 0.5 h / 5 - 10 °C

Reference： [1]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]

26
[ 501-52-0 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: polyphosphoric acid / 0.5 h / 90 °C 2: hydroxylamine hydrochloride / ethanol; water / 0.75 h / Reflux 3: palladium 10% on activated carbon; hydrogen / ethanol / 4 h / 70 °C 4: Candida antarctica lipase B; Pd/AlO(OH); potassium carbonate / toluene / 12 h / 50 °C / Resolution of racemate; Inert atmosphere; Schlenk technique; Enzymatic reaction 5: triethanolamine; sodium hydroxide / water / 6.25 h / 80 °C / Reflux 6: potassium carbonate / acetonitrile / 12 h / 30 °C / Reflux 7: isopropyl alcohol / 0.5 h / 5 - 10 °C

Reference： [1]Ma, Guozhen; Xu, Zhongqi; Zhang, Pengfei; Liu, Jinpo; Hao, Xilin; Ouyang, Jingping; Liang, Ping; You, Song; Jia, Xian [Organic Process Research and Development, 2014, vol. 18, # 10, p. 1169 - 1174]

27
[ 26452-98-2 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Candida rugosa lipase / tetrahydrofuran; aq. phosphate buffer / 24 h / 30 °C / pH 7 / Resolution of racemate; Enzymatic reaction 2: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 3: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 4: potassium carbonate / acetonitrile / 16 h / 60 °C 5: isopropyl alcohol / 1 h / Reflux

Reference： [1]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]

28
[ 6351-10-6 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Thermomyces lanuginosus lipase / hexane / 0.25 h / 35 °C / Inert atmosphere; Resolution of racemate; Enzymatic reaction 2: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 3: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 4: potassium carbonate / acetonitrile / 16 h / 60 °C 5: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 5 steps 1: pseudomonas fluorescens lipase / toluene / 6 h / 30 °C / Inert atmosphere; Resolution of racemate; Enzymatic reaction 2: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 3: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 4: potassium carbonate / acetonitrile / 16 h / 60 °C 5: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 6 steps 1: dmap / dichloromethane / 4 h / 20 °C 2: Candida rugosa lipase / tetrahydrofuran; aq. phosphate buffer / 24 h / 30 °C / pH 7 / Resolution of racemate; Enzymatic reaction 3: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 4: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 5: potassium carbonate / acetonitrile / 16 h / 60 °C 6: isopropyl alcohol / 1 h / Reflux

Reference： [1]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[2]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[3]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]

29
[ 25501-32-0 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 22 h / 0 - 20 °C / Inert atmosphere 2: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 3: potassium carbonate / acetonitrile / 16 h / 60 °C 4: isopropyl alcohol / 1 h / Reflux

Reference： [1]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]

30
(R)-(+)-1-azidoindan [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triphenylphosphine; potassium hydroxide; water / tetrahydrofuran / 24 h / 20 °C 2: potassium carbonate / acetonitrile / 16 h / 60 °C 3: isopropyl alcohol / 1 h / Reflux

Reference： [1]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]

31
[ 10277-74-4 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 16 h / 60 °C 2: isopropyl alcohol / 1 h / Reflux
	Multi-step reaction with 3 steps 1: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 2: sodium hydroxide / toluene / 29 h / 30 °C 3: isopropyl alcohol / 1 h / 55 - 80 °C
	Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 16 h / 60 °C 2: isopropyl alcohol / 1 h / 70 - 75 °C

Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide; dmap / dichloromethane / 15 - 20 °C / Inert atmosphere 2: triphenylsilyl radical; 2-Chlorobenzeneboronic acid / toluene / 24 h / 10 - 15 °C / Inert atmosphere 3: isopropyl alcohol / 1 h / 70 - 75 °C

Reference： [1]De Mattos, Marcos Carlos; De Fonseca, Thiago Sousa; Da Silva, Marcos Reinaldo; De Oliveira, Maria Da Conceição Ferreira; De Lemos, Telma Leda Gomes; De Marques, Ricardo Araújo [Applied Catalysis A: General, 2015, vol. 492, # 1, p. 76 - 82]
[2]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1
[3]Current Patent Assignee: SHANGHAI BOCIMED PHARMACEUTICAL CO LTD - CN109180499, 2019, A
[4]Current Patent Assignee: SHANGHAI BOCIMED PHARMACEUTICAL CO LTD - CN109180499, 2019, A

32
(R)-1-aminoindan (S)-N-acetyl-L-glutaminate (2:1) [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium hydroxide / ethyl acetate / 0.5 h / 20 °C 2: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 3: sodium hydroxide / toluene / 29 h / 30 °C 4: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

33
(R)-1-aminoindan (S)-N-acetyl-L-glutaminate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: ethanol / 2.32 h / 79 °C 2: sodium hydroxide / ethyl acetate / 0.5 h / 20 °C 3: hydrogenchloride / isopropyl alcohol / 0.5 h / 5 - 20 °C / Inert atmosphere 4: sodium hydroxide / toluene / 29 h / 30 °C 5: isopropyl alcohol / 1 h / 55 - 80 °C

Reference： [1]Current Patent Assignee: KRKA DD NOVO MESTO - WO2015/70995, 2015, A1

34
C₁₂H₁₁NO [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triphenylsilyl radical; 2-Chlorobenzeneboronic acid / toluene / 24 h / 10 - 15 °C / Inert atmosphere 2: isopropyl alcohol / 1 h / 70 - 75 °C

Reference： [1]Current Patent Assignee: SHANGHAI BOCIMED PHARMACEUTICAL CO LTD - CN109180499, 2019, A

35
[ 75-75-2 ]
(1R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine hemihydrate [ No CAS ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
92.6%	Stage #1: (1R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine hemihydrate With potassium carbonate In water Large scale; Stage #2: methanesulfonic acid In isopropyl alcohol at 20℃; for 1.5h; Large scale;	3; 6 Example 6 Preparation of rasagiline mesylate: In a 50L glass reactor, 0.662 kg (2.69 mol) of R- () -N- (2-propargyl) -2,3-dihydro-1H-indene-1-amine prepared in the method of Example 5 was added. -L- () -tartrate, dissolved by adding 10L of purified water. The pH was adjusted to about 10 with a 20% potassium carbonate solution, and extracted twice with ethyl acetate. The organic phases were combined, washed once with water, once with saturated brine, dried over anhydrous sodium sulfate, filtered with suction, and evaporated to dryness. Transfer to a 50L glass reactor, add 3.3L of isopropanol to dissolve, and dropwise add a solution consisting of 0.34kg (3.54mol) methanesulfonic acid and 0.7L of isopropanol. After the dropwise addition, the mixture was stirred at room temperature for 1.5 hours, filtered with suction, and dried under vacuum to obtain 0.666 kg of a white solid with a yield of 92.6%. HPLC purity was 99.92%, maximum single impurity was 0.04%; optical purity was 99.77%.

Reference： [1]Current Patent Assignee: QILU PHARMACEUTICAL GROUP CO LTD - CN110776429, 2020, A Location in patent: Paragraph 0049; 0050; 0055; 0056

36
[ 2889348-17-6 ]
[ 161735-79-1 ]
[ 2889347-95-7 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(II) sulfate; (+)-sodium L-ascorbate In water; N,N-dimethyl-formamide	36 Synthesis of Compound 16: General procedure: Add compound 14 sequentially to a 20mL cylindrical glass bottle with a magnet(107mg, 0.5mmol, 1equiv, prepared according to "Synthesis of Compound 14"),1-Phenyl-2-propyn-1-ol (66 mg, 0.5 mmol, 1 equiv.) and DMF (2 mL),Stir to dissolve, take sodium ascorbate (99mg, 0.5mmol, 1equiv.) and dissolve it in water (1mL),Mixed with copper sulfate (50μL, 0.05mmol, 0.1equiv., 1M aqueous solution), the blue color of the solution turns to brown first,After stirring, it turns into light yellow. After mixing evenly, it is added to the reaction system and reacted for 12 hours.After the LC-MS detection reaction was completed, the reaction system was first diluted with water (10 mL), and then extracted with EA (20 mL×3).The combined organic phases were washed with LiCl solution (1M, 100 mL×3), saturated brine (100 mL), dried over Na2SO4, filtered and concentrated.The crude product was subjected to column chromatography (DCM:MeOH=95:5) to obtain a white solid (126 mg, 74% yield).
	With copper(II) sulfate; (+)-sodium L-ascorbate In water; N,N-dimethyl-formamide	36 Synthesis of Compound 16: General procedure: Add compound 14 sequentially to a 20mL cylindrical glass bottle with a magnet(107mg, 0.5mmol, 1equiv, prepared according to "Synthesis of Compound 14"),1-Phenyl-2-propyn-1-ol (66 mg, 0.5 mmol, 1 equiv.) and DMF (2 mL),Stir to dissolve, take sodium ascorbate (99mg, 0.5mmol, 1equiv.) and dissolve it in water (1mL),Mixed with copper sulfate (50μL, 0.05mmol, 0.1equiv., 1M aqueous solution), the blue color of the solution turns to brown first,After stirring, it turns into light yellow. After mixing evenly, it is added to the reaction system and reacted for 12 hours.After the LC-MS detection reaction was completed, the reaction system was first diluted with water (10 mL), and then extracted with EA (20 mL×3).The combined organic phases were washed with LiCl solution (1M, 100 mL×3), saturated brine (100 mL), dried over Na2SO4, filtered and concentrated.The crude product was subjected to column chromatography (DCM:MeOH=95:5) to obtain a white solid (126 mg, 74% yield).

Reference： [1]Current Patent Assignee: SHANGHAI JIAO TONG UNIVERSITY; SHANGHAITECH UNIVERSITY - CN115536638, 2022, A Location in patent: Paragraph 0239; 0252-0258; 0483-0491
[2]Current Patent Assignee: SHANGHAI JIAO TONG UNIVERSITY; SHANGHAITECH UNIVERSITY - CN115536638, 2022, A Location in patent: Paragraph 0239; 0252-0258; 0483-0491

37
[ 70146-15-5 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydroxide / water; dichloromethane / Large scale 2.1: potassium carbonate / acetonitrile / 24 h / 60 - 70 °C / Large scale 2.2: 30 min / 50 - 80 °C / Large scale 3.1: sodium hydroxide / water; dichloromethane / > 10 min / Large scale 3.2: 30 min / 50 - 80 °C / Large scale

Reference： [1]Current Patent Assignee: SHANGHAI FUDAN FORWARD PHARMACEUTICAL CO LTD - CN116082166, 2023, A

38
[ 1135344-69-2 ]
[ 161735-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 3-mercaptopropionic acid; lithium hydroxide / N,N-dimethyl-formamide / 5 h / 25 °C 2: isopropyl alcohol / 3 h / 25 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BOJI MEDICAL TECH CO LTD - CN115947675, 2023, A

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	161735-79-1	MDL No. :	MFCD08460604
Formula :	C₁₃H₁₇NO₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JDBJJCWRXSVHOQ-UTONKHPSSA-N
M.W :	267.34	Pubchem ID :	3052775
Synonyms :	TVP1012 mesylate;(R)-AGN1135 mesylate	Chemical Name :	(R)-N-(Prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine methanesulfonate

Num. heavy atoms :	18
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.38
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	71.91
TPSA :	74.78 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.88 cm/s

Log Po/w (iLOGP) :	2.35
Log Po/w (XLOGP3) :	-1.34
Log Po/w (WLOGP) :	2.24
Log Po/w (MLOGP) :	1.65
Log Po/w (SILICOS-IT) :	2.85
Consensus Log Po/w :	1.55

[ CAS No. 161735-79-1 ] {[proInfo.proName]}

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.77
Solubility :	45.6 mg/ml ; 0.171 mol/l
Class :	Very soluble
Log S (Ali) :	0.27
Solubility :	497.0 mg/ml ; 1.86 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-3.53
Solubility :	0.0789 mg/ml ; 0.000295 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.58

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
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P413
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P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 161735-79-1 ] {[proInfo.proName]}

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