Name: 136236-51-6|(R)-N-(2-Propynyl)-2,3-dihydroinden-1-amine|99+%
Brand: Ambeed
SKU: A981553
Price: 6.0 USD
Availability: InStock
Rating: 91 (27 reviews)

1
[ 915797-28-3 ]
[ 136236-51-6 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 5013 - 5016

2
[ 496-11-7 ]
[ 136236-51-6 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 5013 - 5016

3
[ 217640-41-0 ]
[ 136236-51-6 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 5013 - 5016

4
C₁₀H₁₂O₃S [ No CAS ]
[ 2450-71-7 ]
[ 136236-51-6 ]
N-Propargyl-1(S)-aminoindan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at -29 - 20℃;	Example 8 N-propargyl-1-(R)aminoindan (Rasagiline) Methanesulfonyl anhydride (3.0 g, 17.2 mmol) as a solution in dichloromethane (8 mL+4 mL) was added to a stirred solution of (S)-1-indanol (1.02 g, 7.6 mmol) and triethylamine (4.4 mL, 31.5 mmol) in dichloromethane (20 mL) at -26 C. (internal, -35 C. external) over 10 minutes. During the addition the internal temperature rose to -20 C. The reaction was maintained at -29 C. (internal, -35 C., external) for 45 minutes before propargylamine (5 mL, 78 mmol) was added over 2 minutes. The reaction was allowed to warm slowly to room temperature overnight before being portioned between ethyl acetate (50 mL) and ice-water (75 mL, pH of solution 9.7). The organic layer was concentrated under reduced pressure to afford a brown oil which was partitioned between methyl tert-butyl ether (50 mL) and aqueous hydrochloric acid (1M, 40 mL, pH of solution <1). The aqueous layer was basified to pH>12.5 by addition of aqueous sodium hydroxide solution (2M, 30 mL) before being extracted with ethyl acetate (50 mL+30 mL). The combined final organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound as a brown liquid (0.81 g, 68%). Analysis of this material by chiral GC indicated it to be 46% e.e.

Reference： [1]Patent: US2006/199974,2006,A1 .Location in patent: Page/Page column 8

5
[ 87-69-4 ]
[ 136236-51-6 ]
di-(R-(+)-N-propargyl-1-aminoindan) L-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;Heating / reflux;Product distribution / selectivity;	An example was designed to produce crystals as described in U.S. Pat. No. 6,630,514, example 6A. A first solution of 5.0 g of L-tartaric Acid in 55 ml methanol was prepared and heated to reflux. Then, a solution of 5.7 g of (R)-PAI in 55 ml methanol was added to the first solution while heating and stirring. 322 ml of t-butylmethyl ether was added to the resulting mixture under reflux conditions over 20 minutes. Crystallization of <strong>[136236-51-6]rasagiline</strong> tartrate took place during the addition. The batch was cooled to 17 C. and filtered. The solid product was washed on a filter with t-butylmethyl and dried under vacuum. Dry solid product (7.6 g white crystalline powder) was sampled and analyzed. Analysis: m.p. 176.4-178.4 C., Purity by TLC-one spot (PAI) R-PAI tartrate final product was attained.

Reference： [1]Patent: US2007/112217,2007,A1 .Location in patent: Page/Page column 13

6
[ 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

7
di-(R-(+)-N-propargyl-1-aminoindan) L-tartrate [ No CAS ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; toluene;	59.0 g of wet rasagiline tartrate were mixed with 109.0 g water, and sodium hydroxide (31.5 g of 25% solution) was added. The mixture was stirred and 135 g of Toluene were added. Then the resulting mixture was settled, and the lower aqueous layer was separated and discarded. The upper organic layer was washed twice with water (65 ml and 20 ml) and the solvent was evaporated under vacuum on water bath. The residue after evaporation was dissolved in 56 g of isopropanol and the solvent was evaporated under the same conditions. 29.3 g of rasagiline free base were obtained as a yellow oil.
	With sodium hydroxide; In water; at 20℃;	E) Preparation of (R)-Rasagiline free base50 g of di-(R-(+)-N-propargyl-l-aminoindan)-L-tartrate, 500 mL water and 16 g (40%) sodium hydroxide solution were taken in round bottom flask at room temperature. The reaction mixture was stirred and treated with 250 mL toluene to separate the layers. The separated aqueous layer was extracted with 125 mL toluene at 25C. The combined toluene layer was dried over sodium sulfate and charcoalized with 5 g activated carbon. The reaction mixture was filtered and washed with toluene. The toluene layer was distilled completely under vacuum at 55C to obtain R-(+)-rasagiline base as oil.

Reference： [1]Patent: US2007/112217,2007,A1 .Location in patent: Page/Page column 13
[2]Patent: WO2012/153349,2012,A2 .Location in patent: Page/Page column 30

8
[ 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

9
(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

10
(R-(+)-N-propargyl-1-aminoindan)L-tartarate [ No CAS ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium hydroxide; In water; toluene; at 45℃; for 0.25h;pH 13 - 14;	EXAMPLE 10; Splitting and Precipitation from Isopropanol-Water, Seeded Crystallization from Solution Isopropanol-Water; 100.0 g of Rasagiline Tartrate (1) was suspended in 458 ml deionized water, 229 ml Toluene was added and 46 ml of 25% NaOH solution was introduced at stirring. The mixture was heated to 45 C., stirred at 45 C for 15 minutes and settled at this temperature.Two phases were separated. The lower aqueous phase (pH=13-14) was discarded, the upper toluenic phase was washed with 140 ml deionized water. The resulting emulsion was settled, and two phases were separated. The lower aqueous phase (pH=9-10) was discarded, the toluenic solution was evaporated under vacuum in evaporator.After the solvent evaporation completion 60 ml isopropanol was added to the residue and evaporation was continued.After completion of the evaporation 50 ml of isopropanol was added and distilled out under the same conditions.The residue, oil of R-PAI base (46.4 g), was dissolved in 56 ml isopropanol.The solution was cooled to 16 C. and 147.5 ml of deionized water was added by portions in 3 hr at cooling and stirring. During the addition of water precipitation development was observed and the batch was immediately seeded with crystalline R-PAI base.The resulting suspension was cooled to 2 C., stirred at this temperature overnight and filtered. The solid was washed with water and dried at room temperature under vacuum.48.1 g of Solid dry R-PAI base were attained, with a yield of 96% on oil base. FIG. 12 is a micrograph of this rasagiline base.Analysis: Melting point (by DSC)-41.3 C., S-isomer by HPLC 0.01%, Purity by HPLC-100%, Assay by HPLC-96%
92 - 96%	With sodium hydroxide; In water; toluene; at 45℃; for 0.25h;Product distribution / selectivity;	70.0 g of Rasagiline Tartrate salt (1) suspended in 320 ml deionized water at stirring. The suspension heated to 45 C. and 31 ml of 25% NaOH solution was added with 160 ml Toluene. The mixture was stirred and the resulting emulsion was settled. Two phases were separated. The lower aqueous phase (pH=13-14) was discarded. The upper toluenic phase was washed with 100 ml deionized water at 45 C. and settled. Lower aqueous phase (pH=9-10) was discarded.Toluenic solution was evaporated under vacuum in evaporator, after the solvent evaporation completion 50 ml isopropanol was added to the residue and evaporation was continued.After completion of the evaporation 25 ml of isopropanol was added and distilled out under the same conditions.The residue, oil of R-PAI base (33.9 g), was dissolved in 41 ml isopropanol.The solution was cooled to 15 C. and 58 ml of deionized water was added by portions in 2 hr at cooling and stirring. During the addition of water oily precipitate was formed. The resulting emulsion of oil in water was stirred at 1-3 C. for one hour, no crystallization was observed.The batch was seeded with crystalline Rasagiline base at 1-3 C. and immediate exothermic crystallization took place. 50 ml of water was added to the resulting slurry to improve stirrability and flowability. The batch was stirred for additional 30 minutes and filtered. The solid was washed with water and dried at room temperature under vacuum.31.5 g of solid dry R-PAI base were attained, with a yield of 92% on oil base. FIG. 11 is a micrograph of this rasagiline base.Analysis: Melting point (by DSC)-40.8 C., S-isomer by HPLC 0.02%, Purity by HPLC -100%, Assay by HPLC -98%
	With sodium hydroxide; In water;pH 11.98;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 rasagiline 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%.

Reference： [1]Patent: US2009/318564,2009,A1 .Location in patent: Page/Page column 6-7
[2]Patent: US2008/161408,2008,A1 .Location in patent: Page/Page column 4; 5
[3]Patent: WO2010/59913,2010,A2 .Location in patent: Page/Page column 23-24

Yield	Reaction Conditions	Operation in experiment
		a) dissolving a salt of P(+)-N-propargyl-1-aminoindan in water to form a solution; b) cooling the solution to a temperature of about 0-15C; c) basifying the solution to a pH of about 11 to form a suspension; and d) obtaining the crystalline rasagiline base from the suspension.
		Example 15b - 1.0 mg Rasagiline base This example describes a 1 mg rasagiline base formulations containing malic acid with an extra color coating.
		Rasagiline is melted in the beaker glass at 60-70C and covered with an ice-cold watch glass Result:

12
[ 1166392-44-4 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In denaturated industrial spirit; water; at 80 - 90℃; for 5h;	R-(-)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 <n="12"/>quenched into 2.5 lit water and extracted with 250 ml ethyl acetate three times. The combined organic phase was dried over sodium sulphate & concentrated to about 500ml. 100 gm oxalic acid was added to the ethyl acetate concentrate under stirring at 25-300C and stirred for 1 hr. The resulting precipitated was isolated by filtration to yield 50 gm of (R)- N-propargyl l-indanamine oxalate .

Reference： [1]Patent: WO2009/81148,2009,A1 .Location in patent: Page/Page column 10-11

13
[ 136236-51-6 ]
[ 1175018-74-2 ]
[ 1175018-79-7 ]
[ 1175018-73-1 ]

Yield	Reaction Conditions	Operation in experiment
		1. (R)-PAI base (30 g) and 32% HCl (100 ml) were refluxed for 33 hours (see scheme 2). The reaction mixture was cooled, toluene (150 ml) and water (150 ml) were added and the mixture was stirred for 15 min. The aqueous phase was separated, brought to pH 14 with 47% NaOH and extracted with 150 ml toluene. The organic phase was evaporated to give 36 g dark brown oil which exhibited 3 spots in TLC, two of which were the desired compounds (hexane-4/EA-6,2-Chloro-AAI base: Rf=0.67; cis-3-chloro-AAI base: Rf=0.33, visualized in UV). The third spot had the same Rf as the starting material (0.47) and it was thus thought to be the starting material. However, when trans-3-chloro-AAI (see below) was synthesized it was determined that both the trans and the starting material have the same Rf values under the TLC conditions used. Subsequent testing revealed that third spot was due mostly to PAI and only trace amounts of the trans isomer were formed. 2. The compounds formed in step 1 were separated by filtering-column chromatography [Aldrichimica Acta, 21(4), 106-107 (1998)]. Thus 15 g of the product of step 1 was separated on 400 g silica (Merck type 9385) with a mixture of hexane-7/EA-3 to give 5.6 g pure (R)-2-chloro-AAI (15% overall yield) and 5.0 g cis-3-chloro-AAI base (13% overall yield for steps 1 and 2). 3. To 6.7 g of 2-chloro-AAI base in 100 ml diethyl ether was added 9 ml of 14.5% HCl/ethanol solution. The reaction mixture was stirred for ½ hr at ambient temperature and ½ hr at 5-10 C. The precipitate was filtered, washed with ether and dried in vacuum at 50 C. to give 7.1 g (90% yield) of the pure compound, m.p.=166-169 C. (see scheme 2). The compound exhibited satisfactory NMR and IR spectra which confirmed its structure. 1H-NMR Spectrum The 1H-NMR spectrum is shown in FIG. 1. NMR Peak assignments are listed below: Proton delta (ppm) Multiplicity Coupling Constant (J, Hz) H1 (1H) 4.80 dd 7, 5 H2 (2H) 2.33 m -H3I (1H) 2.82 ddd 17, 8, 6H3II (1H) 3.18 dt 17, 8 H5, H6, H7 (3H) 7.24-7.25 m - H8 (1H) 7.85 d 15 H10 (2H) 3.83, 3.96 AB q 15H12I (1H) 5.65 s -H12II (1H) 5.95 s - H13 (2H) 10.10 broad s - Mass Spectroscopy (MS) The mass spectrum of 2-chloro-AAI-HCl was obtained using a Finnigan 4000 Quadropole Low Resolution Mass Spectrometer, operated in electron impact (EI) mode. The electron impact (EI) spectrum exhibits molecular ions at m/z 207 [M]+. and 206 [M+.-H]+., and characteristic fragments at m/z 171 [M+.-HCl]+., 132 [M+.-C3H4Cl.]+ and 116 [M+.-C3H6ClN.]+. The EI spectrum is in agreement with the molecular formula of 2-chloro-AAI.Elemental Analysis Calculated C: 59.03% H: 6.19% N: 5.74% Found C: 58.93% H: 6.20% N: 5.68% These results correspond to the molecular formula.FT-IR SpectrumThe infrared (FT-IR) spectrum of 2-chloro-AAI-HCl is shown in FIG. 2.

Reference： [1]Patent: US7572834,2009,B1 .Location in patent: Page/Page column 12-13

14
[ 6165-75-9 ]
[ 10277-74-4 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
74.56%	With sodium hydroxide; In water; toluene; at 30 - 50℃;Product distribution / selectivity;	Step (a): Preparation of Rasagiline BaseIn a 1 L round-bottomed flask under nitrogen and equipped with mechanical stirring, were charged 55.00 g of (R)-1-aminoindan, 165 mL of toluene and 147 mL of water. The mixture was stirred at 20-25° C., and subsequently 36.34 g of 50percent aqueous NaOH solution were added dropwise without exceeding 30° C. Once the addition was complete, 81.03 g of propargyl benzenesulfonate were added dropwise to the reaction mixture maintaining the temperature below 30° C. A biphasic brown solution was obtained.The reaction mixture was heated to 45-50° C. and stirred for 4 hours at this temperature. After this period of time, the mixture was cooled down to 20-25° C. and was allowed to stand. The two phases were then separated. 110 mL of toluene and 165 mL of water were added to the stirred organic phase, and the pH was adjusted to 7.5+/-0.2 by the dropwise addition of 35percent aqueous HCl solution (5.50 g were required). 4.125 g of celite were then added, the mixture was stirred for 20 min at 20-25° C. and then filtered, washing the filter cake with 2.x.15 mL of toluene. The filtrate was allowed to stand, and the phases were separated. 165 mL of water were then added to the organic phase, and the pH was adjusted to 7.5+/-0.2 by the dropwise addition of 35percent aqueous HCl solution (0.62 g were required). The mixture was stirred for 10 min, and then the phases were separated.5.00 g of anhydrous sodium sulphate were added to the toluenic phase, the mixture was stirred for 1 h at 20-25° C. and filtered, washing the filter cake with 2.x.15 mL of toluene. The resultant toluenic solution contained 52.72 g of rasagiline base (yield: 74.56percent).

Reference： [1]Patent: US2009/292141,2009,A1 .Location in patent: Page/Page column 3-4

Yield	Reaction Conditions	Operation in experiment
	at 20℃;melt crystallization;Purification / work up;	EXAMPLE 4; Melt Crystallization; 6 g of <strong>[136236-51-6]rasagiline</strong> base liquid in syrup-like form, from example 1, after toluenic evaporation were dissolved in 20 ml of isopropanol. The solution was evaporated in a warm water bath using a rotating evaporator under 12 mbar vacuum until complete solvent removal. The residue was then dissolved in an additional 20 ml of isopropanol and the evaporation was repeated. The resulting residue crystallized spontaneously at room temperature after a few hours. The solid crystalline residue was determined to be <strong>[136236-51-6]rasagiline</strong> base. 5.2 g of the solid crystalline base were attained. The yield was quantitative.
	With sodium hydrogencarbonate; In water; ethyl acetate;pH 8 - 9;Purification / work up;	Example 4; Preparation of Crystalline Form of (R)-N-propargyl-1-aminoindane Free Base(R)-Rasagiline oil (10.1 g, 38 mmoli), obtained according to Example 2, is suspended in a mixture of water (50 ml) and ethyl acetate (200 ml) and treated with a saturated solution of sodium bicarbonate to a pH range comprised between 8 and 9. The phases are separated and the organic one is washed with water (2×50 ml) and filtered on paper, then it is concentrated under reduced pressure to constant weight. The so obtained oily residue is treated with cyclohexane (25 ml) and the so obtained mixture is heated under stirring till a clear solution is obtained. The solution is then slowly cooled and maintained under stirring for about 3 hours at 5 C. Crystals form which are filtered and washed with cyclohexane and dried under vacuum. 5.1 g of Rasagiline free base are obtained in crystalline solid form, with a yield of 78%; m.p. 40-41 C.; and HPLC purity of 99.8%. The water content in the compound determined by titration according to Karl Fischer is about 0.1%. The product has a DSC thermogram as reported in FIG. 4, and an XRPD spectrum as shown in FIG. 3, wherein the most intense diffraction peaks fall at 8.4; 12.3; 12.4; 16.0; 16.8; 20.2; 20.9; 24.9; 25.4 e 26.3+/-0.2 in 2theta.

16
[ 6165-76-0 ]
[ 10277-74-4 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
		(R)-I -Indanamine (1 eq) was taken in dry THF (3 vol) and to the cooled reaction mixture, DBU (1.5 eq) was added dropwise. The reaction mixture was stirred for 1 hour at 0-5C. Propargyl tosylate (1.5 eq) was added dropwise at 0-5C and the mixture stirred for 2 hours at 20-25C. After completion of the reaction, the THF was removed under vacuum and water (3 vol) was added followed by 10% aqueous NaOH (10 vol) and the mixture was stirred for 15 minutes. Extraction was done with DCM, followed by washing with 10% aqueous NaOH and water. The DCM was removed under vacuum at 4O0C to afford rasagiline base.
		R)-1-Aminoindan (1 equivalent) was dissolved in dry THF (3 vol) and cooled to 0-50C. DBU (1.5 equivalents) was added slowly and the resultant mixture stirred for 30 minutes before propargyl tosylate (1.25 equivalents) was added dropwise. The reaction mixture was stirred for 4 hours at 15-200C. After completion of the reaction, the THF was removed under vacuum and water (3 vol) added. The product was extracted with DCM (3 x 3 vol), <n="15"/>followed by washing with 10% aqueous NaOH (2 x 3 vol) and water (2 x 3 vol). The DCM was removed under vacuum at 400C to obtain the product as a light yellow oil.Molar yield = 80-82% Chemical purity = 64.33% (measured by HPLC)

Reference： [1]Patent: WO2010/13048,2010,A1 .Location in patent: Page/Page column 9-10
[2]Patent: WO2009/147432,2009,A1 .Location in patent: Page/Page column 13 - 14

17
[ 136236-51-6 ]
[ 136236-50-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogenchloride; In tert-butyl methyl ether; at 10 - 15℃; for 0.5h;Product distribution / selectivity;	B] The oil obtained in example 2 (10g) was dissolved in methyl tertiary butyl ether (150 ml) and the solution was cooled to 10-15C under stirring. The reaction mixture was purged with hydrochloride gas till the pH of the reaction mixture was acidic and then stirred at 10-15C for 30 min. The product precipitated was collected by filtration, washed with methyl tertiary butyl ether to neutral pH to obtain 12 g (yield: 99 %) of the title compound.; Process for preparation of R(+)-Rasagiline hydrochloride Form I;
	With hydrogenchloride; In diethyl ether;Cooling with ice;Product distribution / selectivity;	1.08 g of <strong>[136236-51-6]rasagiline</strong> free base was dissolved in 10 ml of diethyl ether. The flask was placed in an ice bath (no stirring). HCl (g) was bubbled through the solution (1 minute). After termination a sample of the solid was isolated by filtration and analysed by XRPD: <strong>[136236-51-6]rasagiline</strong> hydrochloride Form I.
	With hydrogenchloride; In water; isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 64; Preparation of Rasagiline Hydrochloride Form IRasagiline base (2.49 g) was dissolved in 2-propanol (10.6 mL). Hydrochloric acid (1.43 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 0.37 g.Analytical data: XRD: Form I, see FIG. 27. IR: see FIG. 28.

Reference： [1]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 13
[2]Patent: US2010/10098,2010,A1 .Location in patent: Page/Page column 5-6
[3]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 11

18
[ 104-15-4 ]
[ 136236-51-6 ]
[ 164294-86-4 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 1h;	Example 5; Preparation of Rasagiline Tosylate Form I150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. p-Toluene sulfonic acid (167 mg) was added, and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was concentrated by evaporation under ambient conditions.Analytical data: XRD: Form I, see FIG. 9. IR: see FIG. 10.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9

19
[ 87-69-4 ]
[ 136236-51-6 ]
(1R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine hemihydrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In isopropyl alcohol; at 40℃; for 2.16667h;	Preparation of <strong>[136236-51-6]rasagiline</strong> hemitartrate In 726 ml of 2-propanol 40.9 g of L ( + ) -tartaric acid (anhydrous) were dissolved under heating to 40C to obtain Solution 1. Separately Solution 2 was prepared by dissolving 110.3 g of <strong>[136236-51-6]rasagiline</strong> free base in 168 ml of 2-propanol under stirring and heating to 40 C. Solution 2 was slowly added under rigorous stirring to Solution 1 within 130 minutes. The obtained suspension was then cooled to 15-20C within 1 hour and further stirred at this temperature for 1 hour. The product was filtered, washed with 70 ml of pre-cooled 2-propanol (having a temperature of 5-10 C) and dried in vacuum drier at 50C and a pressure under 50 mbar . 132.6 of crystalline product was obtained with an assay of 100% and a molar yield of 88.0% (enatiomeric purity 100.00 area%, chromatographic purity 100.00 area%) .
72%	In methanol; butanone; for 1.16667h;Reflux;	Rasagiline free base (5.0 g) and methanol (75 mL) were charged in a flask followed by addition of L-(+)-tartaric acid (1.95 g) and mixture was stirred for 10 minutes. To the mixture, methyl ethyl ketone (25 mL) was added and mixture was heated to reflux temperature followed by stirring at the same for 1 hour. The reaction mixture was cooled to room temperature and maintained at the same for 1 hour. The solid obtained is isolated by filtration and washed with methyl ethyl ketone (10 mL) followed by drying at 60C under vacuum to afford title compound in 72% yield. HPLC purity is 99.98%.
	In isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 51; Preparation of Rasagiline Mixture of Tartrate Form I and Hemitartrate Form IRasagiline base (1.61 g) was dissolved in 2-propanol (6.9 mL). L-Tartaric acid (1.41 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 2.04 g.

Reference： [1]Patent: WO2015/70995,2015,A1 .Location in patent: Page/Page column 28
[2]Patent: EP2610239,2013,A1 .Location in patent: Paragraph 0045; 0046; 0047; 0048
[3]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 10

20
[ 526-95-4 ]
[ 136236-51-6 ]
[ 1204184-71-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	In ethanol; water; for 2h;Product distribution / selectivity;	To a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml of a 1 :1 mixture of ethanol and water 192 mul (0.61 mmol, 1.05 eq) of a 45-50 % w/w solution of gluconic acid in water was added. The clear solution was stirred for 2 h and then evaporated. A solid foam was formed upon drying in high vacuum (211 mg, 0.58 mmol, quant.)
	In water; isopropyl alcohol; at 40℃; for 1h;	Example 3; Preparation of Rasagiline Gluconate Amorphous Form150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. Gluconic acid (343 mg, 50% aqueous) was added and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. MTBE (1 mL) was added and the mixture stirred for an additional 24 hours. The mixture was concentrated by evaporation under ambient conditions.Analytical data: XRD: Amorphous form, see FIG. 5. IR: see FIG. 6.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 8
[2]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9

21
[ 110-16-7 ]
[ 136236-51-6 ]
[ 164294-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 7; Preparation of Rasagiline Maleate Form IRasagiline base (1.2 g) was dissolved in 2-propanol (7.7 mL). Maleic acid (1.22 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 2.3 g.Analytical data: XRD: Form I, see FIG. 13. IR: see FIG. 14.
	In isopropyl alcohol; at 20℃;Heating;	Example 1Process for preparing Rasagiline Maleate Crystalline Form II[0074] A mixture of isopropyl alcohol (30 ml) and maleic acid (2.23 g) was heated to reflux temperature of about 80 to 83C. A solution of <strong>[136236-51-6]rasagiline</strong> base (3 g) dissolved in isopropyl alcohol (30 ml) was added to the hot solution. The reaction mass was cooled gradually to 20 to 25C, and the solid was filtered. The solid obtained was further washed with chilled isopropyl alcohol (10 ml) and dried in vacuum oven at 50 to 55C for 8 hours to yield 2.1 g of <strong>[136236-51-6]rasagiline</strong> maleate crystalline Form II.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/80589,2011,A2 .Location in patent: Page/Page column 13

22
[ 65-85-0 ]
[ 136236-51-6 ]
[ 694436-34-5 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 1h;	Example 1; Preparation of Rasagiline Benzoate Form I150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. Benzoic acid (107 mg) was added and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried at under ambient conditions.Analytical data: XRD: Form I, see FIG. 1. IR: see FIG. 2.
	In n-heptane; isopropyl alcohol;	Example 13; (Rasagiline benzoate) Into solution of <strong>[136236-51-6]rasagiline</strong> base (0.66 g) in 2-propanol (10 ml), benzoic acid (0.47 g) was added. To this solution, w0 ml of heptane was slowly added, then left the solution to evaporate slowly until crystals of <strong>[136236-51-6]rasagiline</strong> benzoate were formed.
	In isopropyl alcohol;	Into solution of <strong>[136236-51-6]rasagiline</strong> base (0.66 g) in 2-propanol (10 ml), benzoic acid (0.47 g) was added. To this solution, wO ml of heptane was slowly added, then left the solution to evaporate slowly until crystals of <strong>[136236-51-6]rasagiline</strong> benzoate were formed.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 8-9
[2]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 10
[3]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 20

23
[ 110-17-8 ]
[ 136236-51-6 ]
[ 164294-87-5 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 53; Preparation of Rasagiline Fumarate Form IRasagiline base (1.80 g) was dissolved in 2-propanol (7.7 mL). Fumaric acid (1.22 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 2.58 g.Analytical data: XRD: Form I, see FIG. 25. IR: see FIG. 26.
	In n-heptane; isopropyl alcohol;	Example 12; (Rasagiline fumarate) Into solution of <strong>[136236-51-6]rasagiline</strong> base (0.54 g) in 2-propanol (15 ml), fumaric acid (0.37 g) was added. To this solution, 20 ml of heptane was slowly added to induce the precipitation of <strong>[136236-51-6]rasagiline</strong> fumarate.
	In isopropyl alcohol;	Into solution of <strong>[136236-51-6]rasagiline</strong> base (0.54 g) in 2-propanol (15 ml), fumaric acid (0.37 g) was added. To this solution, 20 ml of heptane was slowly added to induce the precipitation of <strong>[136236-51-6]rasagiline</strong> fumarate.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 10
[2]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9-10
[3]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 19-20

24
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan hydrogen phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With phosphoric acid; In water; isopropyl alcohol; at 40℃; for 1h;	Example 6; Preparation of Rasagiline Phosphate Amorphous Form150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. Phosphoric acid (86 mg 85% aqueous) was added and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 48 hours at this temperature. The mixture was concentrated by evaporation under ambient conditions.Analytical data: XRD: Amorphous form, see FIG. 11. IR: see FIG. 12.
	With phosphoric acid; In isopropyl alcohol; at 25 - 40℃; for 1h;	3 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 20 mL isopropanol were taken in round bottom flask at 25C. 0.5 g of phosphoric acid was added and heated at 40C with stirring for 1 hours. The reaction mixture was cooled to 25C and stirred for 1 hours. The product was filtered and washed with isopropanol. The product was dried for 12 hours at 55C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> phosphate. The product is characterized by XRD (FIG.5) and IR (FIG.6)

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 25

25
[ 110-15-6 ]
[ 136236-51-6 ]
[ 1204184-69-9 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 18; Preparation of Rasagiline Succinate Form IRasagiline base (1.78 g) was dissolved in 2-propanol (7.6 mL). Succinic acid (1.23 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 2.08 g.Analytical data: XRD: Form I, see FIG. 15. IR: see FIG. 16.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9

26
[ 64-19-7 ]
[ 136236-51-6 ]
[ 164294-89-7 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 2h;Product distribution / selectivity;	Example 29; Preparation of Rasagiline Acetate Mixture of Forms I and IIRasagiline base (2.23 g) was dissolved in 2-propanol (9.5 mL). Acetic acid (0.78 g) was added and the mixture was stirred for 2 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried under vacuum at 40 C. Yield 1.82 g.
	In di-isopropyl ether; for 1h;	To a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1.5 ml diisopropyl ether 33 mul acetic acid was added. After stirring for 1 h, the solvent was removed in vacuo during which precipitation was observed. After drying in high vacuum for 2 h a crystalline solid was obtained.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 10
[2]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 12

27
[ 6556-12-3 ]
[ 136236-51-6 ]
[ 1204184-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 1h;	Example 4; Preparation of Rasagiline Glucuronate Amorphous Form150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. D-glucuronic acid (184 mg) was added and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried at under ambient conditions.Analytical data: XRD: Amorphous form, see FIG. 7. IR: see FIG. 8.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9

28
[ 526-99-8 ]
[ 136236-51-6 ]
[ 1204184-70-2 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 40℃; for 1h;	Example 2; Preparation of Rasagiline Galactarate Form I150 mg of <strong>[136236-51-6]rasagiline</strong> base was dissolved in 1 mL of 2-propanol. Galactaric acid (184 mg) was added and the mixture was stirred for 1 h at 40 C. The mixture was allowed to cool to ambient temperature and stirred for 24 hours at this temperature. The mixture was filtered and dried at under ambient conditions.Analytical data: XRD: Form I, see FIG. 3. IR: see FIG. 4.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 9

29
[ 98-11-3 ]
[ 136236-51-6 ]
[ 1201908-33-9 ]

Yield	Reaction Conditions	Operation in experiment
99.5%	In toluene; at 20℃;Product distribution / selectivity;	Example 67; Preparation of Rasagiline Besylate Form IRasagiline base (10.05 g) was dissolved in toluene (40 mL) at room temperature. Benzenesulfonic acid (9.25 g) was added at room temperature. The mixture was stirred for 5 h. The solid obtained was filtered and dried under vacuum at 40 C. 19.27 g of a white powder was collected (Yield: 99.5%).Analytical data: XRD: substantially identical to FIG. 31. IR: substantially identical to FIG. 32.
	In ethyl acetate; at 10 - 25℃; for 3h;Product distribution / selectivity;	Exam pie- 1:Preparation of (R)-<strong>[136236-51-6]rasagiline</strong> besylate Form-I with larger particle size.50 g of <strong>[136236-51-6]rasagiline</strong> free base and 150 mL ethyl acetate were stirred at 25C in a round bottom flask. 57.7 g of benzene sulfonic acid solution in 180 mL ethyl acetate was added and stirred for 3 hours at about 10C. The product was filtered and washed with ethyl acetate. The <strong>[136236-51-6]rasagiline</strong> besylate thus obtained was dissolved in 315 mL ethyl acetate at about 50C. The stirring should be at the rate of about 100 RPM (rotation per minute). The reaction mixture was cooled to 25C with slow cooling rate and stirred for 18 hours. The reaction mixture was further cooled to about 10C and stirred for 2 hours. The product was filtered and washed with ethyl acetate. The wet-cake was dried at 40C to 45C for 6 to 8 hours. The product was sieved with 60 Mesh to obtain the crystalline Form-I of <strong>[136236-51-6]rasagiline</strong> besylate with larger particle size. The particle size distribution (PSD) was measured by the following method. The product was characterized by XRD (FIG.l), IR (FIG.2) and DSC (FIG.3). The mother liquor obtained after filtration was used for recovery of <strong>[136236-51-6]rasagiline</strong> besylate. The product was sieved through a 60 Mesh. Malvern Laser diffraction, using the Malvern Mastersizer 2000 instrument. The laser diffraction relies on the fact that diffraction angle of light is inversely proportional to particle size. Properties of particles are measured and interpreted as measurements of a sphere (a sphere being the only shape that can be described by one unique number). In addition, the laser diffraction calculates a particle size distribution based around volume terms, thus eliminating particle count from the determination of particle size. The PSD histogram is depicted in FIG. 4.Dispersant Light liquid ParaffinInstrument Malvern Mastersizer S Ver. 2.19Analysis Model PolydispersePresentation 3PAEParticle Refractive Index 1.5Dispersant Refractive Index 1.4Range Lens 300 mmBeam Length 2.35 mmSampler MSISpeed 2000 rpmSweeps 5000Obscuration 10% to 30%Results:The Particle Size distribution provided in FIG.4 is a representative histogram provided herein as reference.

Reference： [1]Patent: US2010/41920,2010,A1 .Location in patent: Page/Page column 11
[2]Patent: WO2012/153349,2012,A2 .Location in patent: Page/Page column 24

30
[ 75-75-2 ]
[ 136236-51-6 ]
N-propargyl-1-(R)-aminoindan mesylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol;Product distribution / selectivity;	Example 13 Resolution of (+/-)-Lambda^-(2-chloroallyl)-2,3-dihydro-lH-indeii-l-amine (XIVa)A 50 mL round bottomed flask was charged with (+/-)-N-(2-chloroallyl)-2,3- dihydro-lH-inden-1 -amine (XIV) (2.4 g, 11.55 mmol), acetone (12 mL) and (+)- O,O'-Dibenzoyl-D-tartaric acid (4.14 g, 1 1.55 mmol). The slurry was heated to reflux for 30 minutes, then cooled to room temperature in two hour. The product was filtered and washed with acetone (2 x 3 mL) at room temperature. The product was dried under reduced pressure at 50 0C for four hours, obtaining 2.84 g of product.The salt was suspended in water (10 mL) and MTBE (7 mL) and 10% aqueous ammonia was added until pH=9. After phase separation the organic layer was dried over sodium sulfate and concentrated under reduced pressure 1.01 g of the title product. The optical purity was determined by transformation into Rasagiline base as described in Example 5 and converting the free base into the mesylate salt with methanesulfonic acid in isopropanol. [OC]D= +5.2 (c=l, EtOH) The enantiomeric purity was upgraded by repeating the crystallization step of the dibenzoyl tartrate from acetone.
	In acetone; at 25 - 35℃; for 1h;Product distribution / selectivity;	3.4 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.7) and IR (FIG.8). The water content is less than 0.5%, which shows it is anhydrous.

Reference： [1]Patent: WO2010/49379,2010,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 25

31
[ 1175018-73-1 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium t-butanolate; In ISOPROPYLAMIDE; at 0 - 5℃; for 2.16667h;Inert atmosphere;Product distribution / selectivity;	Method 2A 100 mL round bottomed flask under nitrogen was charged with (i?)-N-(2- chloroallyl)-2,3-dihydro-lH-inden-l-amine (XIII) (3.0 g, 14.4 mmol), dimethylacetamide (15 mL) and was cooled to 0 0C. To the cooled solution was added sodium tert-butoxide (1.66 g, 17.3 mmol) divided into 4 portions every 30 minutes. After further 40 minutes at 0-5 0C the mixture was diluted with toluene (50 mL) and washed three times with water (15 mL). The organic layer was dried over sodium sulfate and the residue was purified by flash chromatography on silica gel eluting with 5% MeOH in AcOEt, affording 1.99 g of the title compound as a light green oil (82% yield).The mesylate salt was obtained from isopropanol, . [OC]D= +25.2 (c=l, EtOH). 1H NMR (CDCl3, 300 MHz, 298K): 1.69 (bs, IH), 1.82-1.91 (m, IH), 2.28 (t, J=2.5, IH), 2.38-2.41 (m, IH), 2.83 (ddd, J=15.8, 8.2, 6.3, IH), 3.04 (ddd, J=15.9, 8.3, 5.8, IH), 3.50 (dd, J=16.8, 2.5, IH), 3.52 (dd, J=16.9, 2.1 , IH), 4.42(t, J=6, IH), 7.16-7.27 (m, 3H), 7.31-7.38 (m, IH)13C NMR (CDCl3, 75.4 MHz, 298K): 30.6, 33.4, 36.2, 62.0, 71.6, 82.7, 124.3, 125.0, 126.4, 127,7, 143.9, 144.6

Reference： [1]Patent: WO2010/49379,2010,A1 .Location in patent: Page/Page column 44-45

32
[ 1224439-21-7 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
95%		Example 6(R)-N-prop-2-ynyl-2,3-dihydro-lH-inden-l -amine (Rasagiline base)A 50 two-necked flask, was charged, under nitrogen atmosphere, with (i?)-tert- butyl 2,3-dihydro-lH-inden-l-yl(prop-2-ynyl)carbamate (Villa) (300 mg, 1.10 mmol), dissolved in dioxane (11 mL). 37% HCl in water (0.5 mL) was added. After stirring for 30 minutes at room temperature, the reaction mixture was quenched with a saturated solution of NaHCO3 in water (10 mL). Dioxane was removed under reduced pressure and the aqueous layer was extracted with diethyl ether (3 x 20 mL). The organic phase was dried over sodium sulfate and concentrated to a residue, obtaining the title compound (177 mg), as a brown oil. Yield: 95%.1H NMR (CDCl3, 300 MHz, 298K): 1.69 (bs, IH), 1.82-1.91 (m, IH), 2.28 (t,J=2.5, IH), 2.38-2.41 (m, IH), 2.83 (ddd, J=15.8, 8.2, 6.3, IH), 3.04 (ddd, J=15.9, 8.3, 5.8, IH), 3.50 (dd, J=16.8, 2.5, IH), 3.52 (dd, J=16.9, 2.1, IH), 4.42(t, J=6, IH), 7.16- 7.27 (m, 3H), 7.31-7.38 (m, IH)13C NMR (CDCl3, 75.4 MHz, 298K): 30.6, 33.4, 36.2, 62.0, 71.6, 82.7, 124.3,125.0, 126.4, 127,7, 143.9, 144.6

Reference： [1]Patent: WO2010/49379,2010,A1 .Location in patent: Page/Page column 40

Yield	Reaction Conditions	Operation in experiment
		A) Preparation of rasagiline base oil 100.0g of Rasagiline Tartrate was suspended in 458 ml deionized water, 229ml Toluene was added and 46 ml of 25% NaOH solution was introduced at stirring. The mixture was heated to 45C, stirred at 45C for 15 minutes and settled at this temperature. Two phases were separated. The lower aqueous phase (pH=13-14) was discarded, the upper toluenic phase was washed with 140 ml deionized water. The resulting emulsion was settled, and two phases were separated. The lower aqueous phase (pH=9-10) was discarded. The toluenic solution was evaporated under vacuum in evaporator. After the solvent evaporation completion 60 ml isopropanol was added to the residue and evaporation was continued. After completion of the evaporation 50 ml of isopropanol was added and distilled out under the same conditions. The residue, oil of R-PAI base, was obtained.

34
[ 87-69-4 ]
[ 136236-51-6 ]
(1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine L-(+)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; isopropyl alcohol;Reflux;Product distribution / selectivity;	Rasagiline free base (8.0 g), L-(+)-tartahc acid (2.10 g), methanol (56 mL) and isopropyl alcohol (40 mL) are placed in a flask and the mixture is stirred for 5- 15 minutes. The mixture is heated to reflux and maintained for 60-90 minutes under constant stirring. The mixture is then cooled to 25-35C and stirred for 60- 90 minutes. The solid obtained is filtered under vacuum, washed with isopropyl alcohol (8 mL), and dried for 6-8 hours at 60-700C to afford the title compound. HPLC purity is 99.94%
	In methanol; isopropyl alcohol;Reflux;	Rasagiline free base (8.0 g), L-(+)-tartaric acid (2.10 g), methanol (56 mL) and isopropyl alcohol (40 mL) are placed in a flask and the mixture is stirred for 5-15 minutes. The mixture is heated to reflux and maintained for 60-90 minutes under constant stirring. The mixture is then cooled to 25-35 C. and stirred for 60-90 minutes. The solid obtained is filtered under vacuum, washed with isopropyl alcohol (8 mL), and dried for 6-8 hours at 60-70 C. to afford the title compound.HPLC purity is 99.94%

Reference： [1]Patent: WO2010/59913,2010,A2 .Location in patent: Page/Page column 23
[2]Patent: US2011/218360,2011,A1 .Location in patent: Page/Page column 9

35
[ 144-62-7 ]
[ 136236-51-6 ]
(R)-(+)-n-propargyl-1-aminoindane oxalate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.1%	In isopropyl alcohol;	EXAMPLE 2Rasagiline Oxalate; 60 g <strong>[136236-51-6]rasagiline</strong> base were suspended in 885 ml 2-propanol. Then, 32.7 g oxalic acid dissolved in 885 ml 2-propanol were added. The mixture was allowed to stand in a refrigerator overnight, then filtrated and subsequently washed with 100 ml cooled 2-propanol. The residue was dried in a drying cabinet at 45 C. Yield: 87.6 g (93.1% of the theoretical) white crystals; water content (Karl Fischer): about 0.1%; melting point 204 C. (clear, brown melt); TFC: peak at 209.52 C.; [alpha]D20: +28.9 (2% in ethanol); elemental analysis: C=64.39% (theoretical: 64.36%), H=5.91% (theoretical: 5.79%), N=5.43% (theoretical: 5.36%).

Reference： [1]Patent: US2010/234636,2010,A1 .Location in patent: Page/Page column 4

36
[ 56-84-8 ]
[ 136236-51-6 ]
[ 1260684-36-3 ]

Yield	Reaction Conditions	Operation in experiment
	In water; isopropyl alcohol; at 0 - 70℃; for 1h;	82 mg L-aspartic acid was dissolved in 7 ml water at 700C. A solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 2 ml isopropanol was added at this temperature. The solution remained clear, was cooled to O0C and stirred at this temperature for 1 h. Since no turbidity was observed the solvents were removed in vacuo. The residual clear oil partially crystallised on standing. After a slurry wash with acetone, a white crystalline material was obtained (40 mg). Analysis revealed that this material was aspartic acid.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 9

37
[ 112-80-1 ]
[ 136236-51-6 ]
[ 1260684-14-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	In di-isopropyl ether; for 1.5h;Inert atmosphere;Product distribution / selectivity;	To a solution of 4.5 g (26.3 mmol) <strong>[136236-51-6]rasagiline</strong> in 120 ml diisopropyl ether 8.3 ml (26.3 mmol, 1.0 eq) oleic acid was added under nitrogen. After stirring for 90 min, the solvent was removed in vacuo at 300C. Drying on the rotary evaporator was continued for another 2 h at this temperature. Drying in high vacuum for 2 h yielded 11.2 g (24.7 mmol, 94 %) of a yellow oil.1H NMR (de-DMSO, 300 MHz): delta = 7.31 (m, 1 H, PhH), 7.21-7.10 (m, 3 H, PhH), 5.30 (t, J = 4.8 Hz, 2 H, olefin-H), 4.25 (t, J = 6.3 Hz, 1 H, N-CH), 3.37 (d, J = 2.8 Hz, 2 H, N-CH2), 3.04 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.90 (m, 1 H, ring-CH), 2.71 (quint, J = 15.0, 7.5 Hz, 1 H, ring-CH), 2.26 (m, 1 H, ring-CH), 2.15 (t, J = 7.5 Hz, 2 H, C(O)CH2), 1.97 (m, 4 H, 2 x C=CHCH2), 1.76 (m, 1 H, ring-CH), 1.48 (brt, J = 7.2 Hz, 2 H, C(O)CH2CH2), 1.25-1.21 (s, 18 H, 9 x CH2), 0.84 (t, J = 6.3 Hz, 3 H, omega-CH3). The integrals show a ratio of amine/acid = 1 :1.IR: v = 2925.56, 2854.04, 1712.92, 1615.04, 1551.28, 1459.31 , 1402.52 cm"1. IR indicates protonation of the amine.HPLC (by area%): 99.80 %.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 14-15

38
[ 151-21-3 ]
[ 136236-51-6 ]
[ 1260684-44-3 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In water; for 2h;	167 mg (0.58 mmol, 1.0 eq) sodium lauryl sulphate was dissolved in 1 ml water and 40 mul acetic acid followed by addition of a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml acetone. After stirring for 2 h the solution was evaporated in vacuo. The residue was reslurried in 2 ml acetone and 1 ml methanol. The mixture was filtered through cotton wool to remove sodium acetate. The filtrate was evaporated to yield a solid foam.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 10

39
[ 849585-22-4 ]
[ 136236-51-6 ]
[ 1260684-39-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	In acetone; for 2h;	To a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml acetone 44 mul (0.58 mmol, 1.0 eq) DL-lactic acid was added. The formation of a white, milky precipitate was observed. After stirring for 2 h, a waxy precipitate was formed on the glass wall. The supernatant was removed and the wax was washed with 2 ml acetone. On drying in high vacuum (6 h) a white, sticky solid foam was obtained (150 mg, 0.58 mmol, quant.).

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 9

40
[ 77-92-9 ]
[ 136236-51-6 ]
[ 1236349-13-5 ]

Yield	Reaction Conditions	Operation in experiment
57%	In acetone;	To a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml acetone a solution of 117 mg (0.61 mmol, 1.05 eq) anhydrous citric acid in 1 ml warm acetone was added. The solution became turbid during addition forming a waxy precipitate. The supernatant was removed and the wax was washed with 2 ml acetone twice using sonication. On drying in high vacuum a white solid foam was obtained. Drying was continued for 6 h on high vacuum (120 mg, 0.33 mmol, 57 %).
	In methanol;	Example 1 - Preparation of Mono-<strong>[136236-51-6]rasagiline</strong> citrate; SaltIn the following experiment, <strong>[136236-51-6]rasagiline</strong> base was mixed with citric acid (1:1 mohmol) and then methanol was added to the mixture. After stirring and complete dissolution of solids, the solution was evaporated under vacuum in rotary evaporator at bath temperature 60C. The resulting foamy substance was dried under vacuum to obtain mono-<strong>[136236-51-6]rasagiline</strong> citrate.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2012/15946,2012,A1 .Location in patent: Page/Page column 16

41
[ 802294-64-0 ]
[ 136236-51-6 ]
[ 1260684-10-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	In di-isopropyl ether; for 1.5h;	To a solution of 43 mg (0.58 mmol, 1.0 eq) propionic acid in 0.5 ml diisopropyl ether a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 0.5 ml diisopropyl ether was added. After stirring for 90 min the solvent was removed in vacuo. The residue was dried in high vacuum for 5 h to yield a thick oil (143 mg, 0.58 mmol, quant.). 1H NMR (CJ6-DMSO, 400 MHz): delta = 7.30 (m, 1 H, PhH), 7.24-7.10 (m, 3 H, PhH), 4.25 (t, J = 6.4 Hz, 1 H, N-CH), 3.38 (dd, J = 2.4, 1.2 Hz, 2 H, N-CH2), 3.09 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.90 (m, 1 H, ring-CH), 2.72 (quint., J = 15.0, 7.6 Hz, 1 H, ring-CH), 2.28 (m, 1 H, ring-CH), 2.19 (q, J = 7.6 Hz, 2 H, C(O)CH2), 1.74 (m, 1 H, ring-CH), 0.99 (t, J = 7.6 Hz, 3 H, CH3). The integrals confirm a ratio of amine/acid = 1 :1. IR: v = 3291.7, 2930.4, 2852.3, 1716.1 , 1599.2, 1560.0, 1459.1 , 754.7, 648.3 cm'1. IR indicates protonation of the amine.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 11-12

42
[ 136236-51-6 ]
[ 109-52-4 ]
[ 1260684-09-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	In di-isopropyl ether; for 1.5h;	To a solution of 60 mg (0.58 mmol, 1.0 eq) pentanoic acid in 0.5 ml diisopropyl ether a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 0.5 ml diisopropyl ether was added. After stirring for 90 min the solvent was removed in vacuo. The residue was dried in high vacuum for 5 h to yield a thick oil (158 mg, 0.58 mmol, quant.). 1H NMR (d6-DMSO, 400 MHz): delta = 7.30 (m, 1 H, PhH), 7.23-7.12 (m, 3 H, PhH), 4.24 (t, J = 6.4 Hz, 1 H, N-CH), 3.37 (d, J = 2.4 Hz, 2 H, N-CH2), 3.09 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.89 (m, 1 H, ring-CH), 2.72 (quint., J = 15.0, 7.6 Hz, 1 H, ring-CH), 2.27 (m, 1 H, ring-CH), 2.19 (t, J = 7.4 Hz, 2 H, C(O)CH2), 1.74 (m, 1 H, ring-CH), 1.47 (m, 2 H, C(O)CH2CH2), 1.29 (m, 2 H, CH3CH2), 0.86 (t, J = 7.6 Hz, 3 H, CH3). The integrals confirm a ratio of amine/acid = 1 :1.IR: v = 3291.5, 2957.6, 2932.9, 1712.3, 1606.7, 1552.1 , 1458.4, 754.9, 661.6 crr1. IR indicates protonation of the amine.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 11

43
[ 142-62-1 ]
[ 136236-51-6 ]
[ 1260684-13-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	In di-isopropyl ether; for 1.5h;Inert atmosphere;	To a solution of 7.0 g (40.9 mmol) <strong>[136236-51-6]rasagiline</strong> in 120 ml diisopropyl ether 5.1 ml (40.9 mmol, 1.0 eq) hexanoic acid was added under nitrogen. After stirring for 90 min, the solvent was removed in vacuo at 300C. Drying on the rotary evaporator was continued for another 2 h at this temperature. Drying in high vacuum for 2 h yielded 11.6 g (40.3 mmol, 99 %) of a light brown oil.1H NMR (de-DMSO, 300 MHz): delta = 7.31 (m, 1 H, PhH), 7.21-7.10 (m, 3 H, PhH), 4.25 (t, J = 6.3 Hz, 1 H, N-CH), 3.37 (d, J = 2.8 Hz, 2 H, N-CH2), 3.06 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.90 (m, 1 H, ring-CH), 2.74 (quint., J = 15.0, 7.5 Hz, 1 H, ring-CH), 2.28 (m, 1 H, ring-CH), 2.17 (t, J = 7.5 Hz, 2 H, C(O)CH2), 1.74 (m, 1 H, ring-CH), 1.48 (quint., J = 14.4, 7.2 Hz, 2 H, C(O)CH2CH2), 1.25-1.21 (m, 4 H, 2 x CH2), 0.85 (t, J = 6.6 Hz, 3 H, U)-CH3). The integrals confirm a ratio of amine/acid = 1 :1.IR: v = 2956.13, 2931.46, 2859.22, 1714.75, 1608.88, 1551.24, 1459.09, 1401.15 cnr1. IR indicates protonation of the amine.HPLC (by area%): 99.63 %.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 14

44
[ 124-07-2 ]
[ 136236-51-6 ]
[ 1260684-12-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	In di-isopropyl ether; for 1.5h;Inert atmosphere;Product distribution / selectivity;	To a solution of 6.0 g (35.0 mmol) <strong>[136236-51-6]rasagiline</strong> in 120 ml diisopropyl ether 5.5 ml (35.0 mmol, 1.0 eq) octanoic acid was added under nitrogen. After stirring for 90 min, the solvent was removed in vacuo at 3O0C. Drying on the rotary evaporator was continued for another 2 h at this temperature. Drying in high vacuum for 2 h yielded 10.9 g (34.6 mmol, 99 %) of a light brown oil.1H NMR (d6-DMSO, 300 MHz): delta = 7.31 (m, 1 H, PhH), 7.21-7.13 (m, 3 H, PhH), 4.25 (t, J = 6.3 Hz, 1 H, N-CH), 3.37 (d, J = 2.8 Hz, 2 H, N-CH2), 3.05 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.91 (m, 1 H, ring-CH), 2.74 (quint, J = 15.0, 7.5 Hz, 1 H, ring-CH), 2.28 (m, 1 H, ring-CH), 2.17 (t, J = 7.5 Hz, 2 H1 C(O)CH2), 1.76 (m, 1 H, ring-CH), 1.48 (bit, J = 6.9 Hz, 2 H, C(O)CH2CH2), 1.24 (S, 8 H, 4 x CH2), 0.85 (t, J = 6.3 Hz, 3 H, omega-CH3). The integrals confirm a ratio of amine/acid = 1 :1.IR: v = 2954.71 , 2927.69, 2855.59, 1713.63, 1607.76, 1548.75, 1459.54, 1401.97 cm"1. IR indicates protonation of the amine.HPLC (by area%): 99.58 %.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 13

45
[ 334-48-5 ]
[ 136236-51-6 ]
[ 1260684-11-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	In di-isopropyl ether; for 1.5h;Inert atmosphere;	To a solution of 6.0 g (35.0 mmol) <strong>[136236-51-6]rasagiline</strong> in 120 ml diisopropyl ether 6.75 ml (35.0 mmol, 1.0 eq) decanoic acid was added under nitrogen. After stirring for 90 min, the solvent was removed in vacuo at 3O0C. Drying on the rotary evaporator continued for another 2 h at this temperature. Drying in high vacuum for 2 h yielded 11.5 g (33.5 mmol, 96 %) of a yellow oil.1H NMR (d6-DMSO, 300 MHz): delta = 7.32 (m, 1 H, PhH), 7.21-7.12 (m, 3 H, PhH), 4.25 (t, J = 6.3 Hz, 1 H, N-CH), 3.37 (d, J = 2.4 Hz, 2 H, N-CH2), 3.05 (t, J = 2.4 Hz, 1 H, alkynyl-H), 2.91 (m, 1 H, ring-CH), 2.74 (quint., J = 15.0, 7.5 Hz, 1 H, ring-CH), 2.28 (m, 1 H, ring-CH), 2.17 (t, J = 7.5 Hz, 2 H, C(O)CH2), 1.76 (m, 1 H, ring-CH), 1.47 (brt, J = 6.9 Hz, 2 H, C(O)CH2CH2), 1.23 (s, 12 H, 6 x CH2), 0.85 (t, J = 6.3 Hz, 3 H, omega-CH3). The integrals confirm a ratio of amine/acid = 1 :1.IR: v = 2925.62, 2854.60, 1713.00, 1616.02, 1548.12, 1459.44, 1401.58 cm"1. IR indicates protonation of the amine. HPLC (by area%): 99.81 %.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 12-13

46
[ 60-33-3 ]
[ 136236-51-6 ]
[ 1260684-08-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	In acetone; for 2h;	To a solution of 300 mg <strong>[136236-51-6]rasagiline</strong> (1.75 mmol) in 6 ml acetone 0.54 ml (1.75 mmol, 1.0 eq) linoleic acid was added. After stirring for 2 h the solvent was evaporated at 300C in vacuo. Drying in high vacuum led to a brownish oil (0.77 g, 1.75 mmol, quant.).IR: v = 3308.9, 3009.2, 2927.2, 2854.8, 1712.2, 1615.9, 1548.5, 1459.5, 753.8 crrf1. IR indicates protonation of the amine.

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 11

47
[ 577-11-7 ]
[ 136236-51-6 ]
[ 1260684-42-1 ]

Yield	Reaction Conditions	Operation in experiment
100%		Sodium docusate was converted into the corresponding acid by aqueous work-up with 1 M hydrochloric acid and dichloromethane. The organic phase was dried and evaporated. 245 mg (0.58 mmol) of the resulting acid was dissolved in 1 ml acetone and added to a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml acetone. After stirring for 2 h the solvent was evaporated to yield a solid waxy material (365 mg, 0.58 mmol, quant.).

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 10

48
[ 81-07-2 ]
[ 136236-51-6 ]
[ 1260684-40-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	In acetone;	To a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1.5 ml acetone a solution of 106 mg (0.58 mmol, 1.0 eq) saccharin in 1.5 ml acetone was added. The solution was stirred over night. Evaporation of the solvent in vacuo and drying in high vacuum yielded a white, solid foam (208 mg, 0.58 mmol, quant.).
63%	In isopropyl alcohol; at 20℃;Cooling with ice;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base are dissolved in 6.0 ml of isopropyl alcohol whereupon 534 mg (2.915 mmoles) of saccharine are added. The solution is allowed to stand overnight at room temperature. The solvent is evaporated in vacuo, the residue is treated with a mixture of diisopropyl acetate and diisopropyl ether and the precipitated solid substance is filtered. Thus 826 mg of the title compound are obtained which is dissolved in 4.0 ml of hot isopropanol, to the solution 5.0 ml of diisopropyl ether are added and the product is crystallized by slow cooling of the solution. The suspension is cooled with icecold water, the precipitated crystals are filtered off and finally washed with cold diisopropyl ether. Yield 653 mg (63 %), off-white crystals.Melting point: 107.0-108..5 CElementary analysis for the Formula: C19H18N2O3S (354.43) :Calculated [%] C: 64.39 H: 5.12 N: 7.90 S: 9.05 O: 13.54 Found [%] C: 64.34 H: 5.08 N: 7.98 S: 9.13IR (KBr): 3289, 2953, 2830, 2731, 1622, 1583, 1455, 1271, 1152, 1118 cm"1.1H-NMR (DMSO-t , 400 MHz) delta 7.66 (m, 1H), 7.60 (m, 4H), 7.38 (m, 1H), 7.37 (m, 1H), 7.31 (t, 1H), 4.81 (dd, 1H, J = 7.3, 4.2 Hz), 4.00 (m, 2H), 3.75 (m, 1H), 3.10 (m, 1H), 2.89 (m, 1H), 2.43 (m, 1H), 2.19 (m, lH) ppm.HPLC purity: >99.8%[a] 22D =+13.5 (c=l; EtOH)

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 21-22

49
[ 2211-98-5 ]
[ 136236-51-6 ]
[ 1260684-46-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With acetic acid; In water; acetone; for 2h;	202 mg (0.58 mmol, 1.0 eq) sodium 4-dodecylbenzenesulfonate was dissolved in 1 ml water and 40 mul acetic acid was added. The resulting solution was added to a solution of 100 mg (0.58 mmol) <strong>[136236-51-6]rasagiline</strong> in 1 ml acetone. After stirring for 2 h, the solution was evaporated in vacuo. The residue was reslurried in 2 ml acetone. The mixture was filtered through cotton wool to remove sodium acetate. The filtrate was evaporated to yield a solid foam (300 mg, 0.58 mmol, quant.).

Reference： [1]Patent: WO2011/3938,2011,A1 .Location in patent: Page/Page column 10

50
[ 140-10-3 ]
[ 136236-51-6 ]
rasagiline cinnamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether;	Example 10; (Rasagiline cinnamate) Rasagiline base (0.55 g) was dissolved in diethyl ether (20 ml) and trans-cinnamic acid (0.48g) was added to the solution. The solution was left to slowly evaporate until crystals of <strong>[136236-51-6]rasagiline</strong> cinnamate were formed.
	In diethyl ether;	Rasagiline base (0.55 g) was dissolved in diethyl ether (20 ml) and trans-cinnamic acid (0.48g) was added to the solution. The solution was left to slowly evaporate until crystals of <strong>[136236-51-6]rasagiline</strong> cinnamate were formed.

Reference： [1]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 19

51
[ 611-71-2 ]
[ 136236-51-6 ]
[ 1309125-28-7 ]

Yield	Reaction Conditions	Operation in experiment
	In n-heptane; isopropyl alcohol;	Example 14; (Rasagiline D-mandelate) Rasagiline base (0.69g) was dissolved in 2-propanol (20 ml) and was combined with solution of D-(-)-mandelic acid (0.61 g) in 2-propanol (10 ml). To this combined solution 20 ml of heptane was slowly added, then left the solution to evaporate slowly until crystals of <strong>[136236-51-6]rasagiline</strong> D-mandelate formed.
	In isopropyl alcohol;	Rasagiline base (0.69g) was dissolved in 2-propanol (20 ml) and was combined with solution of D-(-)-mandel ic acid (0.61 g) in 2-propanol (1 0 ml ). To th is combined solution 20 ml of heptane was slowly added, then left the solution to evaporate slowly until crystals of <strong>[136236-51-6]rasagiline</strong> D-mandelate formed.

Reference： [1]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 10
[2]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 20

52
[ 3144-16-9 ]
[ 136236-51-6 ]
[ 1309125-24-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	In methanol; at 20℃; for 1h;	(<strong>[136236-51-6]rasagiline</strong> (S)-camsylate, compound of the Formula VI) 500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base and 677 mg (2.915 mmoles) of (1 £)-(+)- 10-camphorsulfonic acid are dissolved in 1.0 ml of methanol at room temperature. The solution is stirred for an hour, then evaporated in vacuo and the residue is treated with diisopropyl ether. The solid product is filtered and washed with diisopropyl ether. Thus 1.094 g of a light yellow beige crude salt is obtained which is crystallized from 4.5 ml of hot isopropyl alcohol. The suspension thus obtained is cooled in an icecold water-bath. The precipitated crystals are filtered and finally washed with cold diisopropyl ether.Yield: 932 mg (79 %), off-white crystalsMelting point: 168.5-170.0 CElementary analysis for the Formula: C22H29N04S (403..54):Calculated [%] C: 65.48 H: 7.24 N: 3.47 S: 7.95 0: 15.86 Found [%] C: 65.33 H: 7.06 N: 3.36 S: 8.17IR (KBr): 3455, 3302, 2959, 2656, 1736, 1479, 1220, 1169,1038 cm"1.1H-NMR (DMS0-< 400 MHz) delta 9.46 (s, 2H), 7.61 (d, 1H, J = 7.5 Hz), 7.38 (m, 1H), 7.37 (m, 1H), 7.31 (m, 1H), 4.82 (dd, 1H, J - 7.7, 4.3 Hz), 4.02 (dd, 1H, J = 17.0, 2.5 Hz), 3.98 (dd, 1H, J - 17.0, 2.5 Hz), 3.76 (t, 1H, J = 2.5 Hz), 3.1 1 (m, 1H), 2.90 (m, 1H), 2.89 (d, 1H, J = 14.8 Hz), 2.68 (m, 1H), 2.44 (m, 1H), 2.39 (d, 1H, J = 14.8 Hz), 2.23 (m, 1H), 2.21 (m, 1H), 1.94 (t, 1H, J = 4.5 Hz), 1.86 (m, 1H), 1.79 (d, 1H, J = 18.5 Hz), 1.29 (m, 1H), 1.27 (m, 1H), 1.05 (s, 3H), 0.74 (s, 3H) ppm.HPLC purity: >99.8%[a] 22D =+36.7 (c=l; EtOH)
	In n-heptane; isopropyl alcohol;	Example 3; (Rasagiline (+)-camphor-1 0-sulfonate) Rasagiline base (0.50g) was dissolved in 2-propanol (10 ml) and was combined with solution of (+)-camphor-10-sulfonic acid (0.68 g) in 2-propanol (5 ml). To this combined solution 20 ml of heptane was slowly added, and left to evaporate slowly. After several hours crystals of <strong>[136236-51-6]rasagiline</strong> (+)-camphor-1 0-sulfonate formed.

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 28-29
[2]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9

53
[ 17199-29-0 ]
[ 136236-51-6 ]
[ 1309125-23-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	In isopropyl alcohol; at 20℃;Heating; Cooling with ice;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base are dissolved in 3.3 ml of isopropanol whereupon a hot solution of 444 mg (2.918 mmoles) of (S)-mandelic acid and 3.4 ml of isopropanol is added. The warm solution is cooled to room temperature under stirring, whereby intensive crystal formation begins. The suspension is cooled with icecold water, the precipitated crystals are filtered.Yield 800 mg (85 %), white crystalsMelting point: 111.5-112.5 CElementary analysis for the Formula: C2oH21N03 (323.40):Calculated [%] C: 74.28 H: 6.55 N: 4.33 0: 14.84 Found [%] C: 74.09 H: 6.44 N: 4.27IR (KBr): 3406, 3233, 2129, 1639, 1560, 1454, 1344, 1189, 1088, 1063 cm"1.1H-NMR (DMSO-i¾, 400 MHz) delta 7.41 (d, 2H), 7.35 (d, 1H), 7.33 (t, 2H), 7.26 (t, 1H), 7.23 (d, 1H), 7.19 (t, 1H), 7.16 (t, 1H), 4.95 (s, 1H), 4.31 (t, 1H, J = 6.4 Hz), 3.44 (d, 2H, J = 2.4 Hz), 3.13 (t, 1H, J = 2.4 Hz), 2.95 (m, 1H), 2.75 (m, 1H), 2.29 (m, 1H), 1.81 (m, 1H) ppm. HPLC purity: >99.8%[a] 22D = +66.8 (c-l; EtOH)
	In n-heptane; isopropyl alcohol;	Example 1; (Rasagiline L-mandelate) Rasagiline base (0.77g) was dissolved in 2-propanol (10 ml) and was combined with solution of L-(+)-mandelic acid (0.68 g) in 2-propanol (10 ml). To this combined solution 20 ml of heptane was slowly added, and thus formed crystalline precipitate was filtered to give <strong>[136236-51-6]rasagiline</strong> L-mandelate.
	In ethyl acetate; isopropyl alcohol; at 20℃; for 24h;Heating;	Example 2Process for preparing Rasagiline Mandelate Crystalline Form I[0075] A mixture of isopropyl alcohol (30 ml) and L-(+)-mandelic acid (2.9 g) was heated to reflux temperature of about 80 to 83C. A solution of <strong>[136236-51-6]rasagiline</strong> base (3 g) dissolved in ethyl acetate (30 ml) was added to the hot solution. The reaction mass was cooled gradually to about 20 to 25C and stirred for 24 hours at 25 to 30C. The resulting solid was filtered, washed with chilled isopropyl alcohol (10 ml) and then dried in vacuum oven at 50 to 55C for 8 hours to yield 3.9 g of <strong>[136236-51-6]rasagiline</strong> mandelate crystalline Form I.

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 19
[2]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 8
[3]Patent: WO2011/80589,2011,A2 .Location in patent: Page/Page column 13

54
[ 65-86-1 ]
[ 136236-51-6 ]
[ 1309125-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	In water; isopropyl alcohol;Heating;	Example 9; (Rasagiline orotate) Rasagiline base (1.19 g) was dissolved in 2-propanol (120 ml), then <strong>[65-86-1]orotic acid</strong> (1.08 g) was added, followed by water (6 ml), then a suspension was heated until clear solution was momentarily obtained, then left to cool to r.t and crystallize to give rasagiline orotate.
	In water; isopropyl alcohol;Heating;	Rasagiline base (1 .1 9 g) was dissolved in 2-propanol (120 ml), then <strong>[65-86-1]orotic acid</strong> (1 .08 g) was added, followed by water (6 ml), then a suspension was heated until clear solution was momentarily obtained, then left to cool to r.t and crystallize to give rasagiline orotate.

Reference： [1]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 19

55
[ 35963-20-3 ]
[ 136236-51-6 ]
[ 1309125-29-8 ]

Yield	Reaction Conditions	Operation in experiment
19%	In methanol; at 20℃; for 1h;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base and 677 mg (2.915 mmoles) of (li?)-10-camphorsulfonic acid are dissolved in 1.0 ml of methanol. The solution is stirred for an hour, evaporated to dryness in vacuo and the residue is treated with diisopropyl ether. The solid product is filtered off and washed with diisopropyl ether. Thus 1.051 g of a beige coloured crude salt is obtained which is crystallized from a mixture of hot isopropyl-alkohol and diisopropyl ether. The suspension thus formed is cooled with an ice-water bath, the precipitated crystals are filtered and finally washed with cold diisopropyl ether.Yield 219 mg (19 %), off-white crystals.Mp,: 140-142C.Elementary analysis for the Formula: C22H29N04S (403.54):Calculated [%] C: 65.48 H: 7.24 N: 3.47 S: 7.95 O: 15.86 Found [%] C: 65.23 H: 7.00 N: 3.34 S: 8.14IR (KBr): 3442, 3228, 2958, 2806, 1745, 1482, 1230, 1 167,1041 cm"1.1H-NMR (DMSO-i¾, 400 MHz) delta 9.47 (s, 2H), 7.61 (d, 1H, J = 7.6Hz), 7.38 (m, 1H), 7.37 (m, 1H), 7.31 (m, 1H), 4.82 (dd, 1H, J = 7.7, 4.3 Hz), 4.02 (dd, 1H, J = 17.6, 2.6 Hz), 3.98 (dd, 1H, J = 17.6, 2.5 Hz), 3.76 (t, 1H, J = 2.5 Hz), 3.12 (m, 1H), 2.90 (m, 1H), 2.89 (d, 1H, J= 14.8 Hz), 2.67 (m, 1H), 2.44 (m, 1H), 2.39 (d, 1H, J = 14.8 Hz), 2.23 (m, 1H), 2.21 (m, 1H), 1.94 (t, 1H, J = 4.6 Hz), 1.85 (m, 1H), 1.79 (d, 1H, J = 18.1 Hz), 1.29 (m, 1H), 1.27 (m, 1H), 1.05 (s, 3H), 0.74 (s, 3H) ppm.HPLC purity: >99.8 %[a] 22D = +l l,l (c=l; EtOH)
	In n-heptane; isopropyl alcohol;	Example 15; (Rasagiline (-)-camphor-10-sulfonate) Rasagiline base (0.57g) was dissolved in 2-propanol (10 ml) and was combined with solution of (-)-camphor-10-sulfonic acid (0.77 g) in 2-propanol (5 ml). To this combined solution 20 ml of heptane was slowly added, and left to evaporate slowly. After several hours crystals of <strong>[136236-51-6]rasagiline</strong> (-)-camphor-10-sulfonate formed.
	In isopropyl alcohol;	Rasagiline base (0.57g) was dissolved in 2-propanol (10 ml) and was combined with solution of (-)-camphor-I O-sulfonic acid (0.77 g) in 2-propanol (5 ml). To this combined solution 20 ml of heptane was slowly added, and left to evaporate slowly. After several hours crystals of <strong>[136236-51-6]rasagiline</strong> (-)-camphor-I O-sulfonate formed.

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 31-32
[2]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 10
[3]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 20

56
[ 136236-51-6 ]
[ 86-48-6 ]
[ 1309125-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	In n-heptane; isopropyl alcohol;	Example 11; (Rasagiline 1-hydroxy-2-naftoate) Rasagiline base (0.60 g) was dissolved in 2-propanol (15 ml) then 1-hydroxy-2-naftoic acid (0.66 g) was added. To this solution 20 ml of heptane was slowly added and the solution was left to crystallize, to give rasigaline 1-hydroxy-2-naftoate.
	In isopropyl alcohol;	Rasagiline base (0.60 g) was dissolved in 2-propanol (15 ml) then 1 -hydroxy-2- naftoic acid (0.66 g) was added. To this solution 20 ml of heptane was slowly added and the solution was left to crystallize, to give rasigaline 1 -hydroxy-2-naftoate.

Reference： [1]Patent: EP2325159,2011,A1 .Location in patent: Page/Page column 9
[2]Patent: WO2011/64216,2011,A1 .Location in patent: Page/Page column 19

57
[ 69-72-7 ]
[ 136236-51-6 ]
[ 1313048-99-5 ]

Yield	Reaction Conditions	Operation in experiment
66%	In isopropyl alcohol;Heating;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base are dissolved in 3.8 ml of isopropyl alcohol at room temperature, whereupon a hot solution of 403 mg (2.918 mmoles) of 2-hydroxy-benzoic acid and 1.4 ml of isopropyl alcohol is added. The solution is mixed, cooled, whereupon the precipitated crystals are filtered, washed with cold alcohol and dried on the air.Yield: 596 mg (66 %), off-white crystals.Melting point: 120.5-121.5 CElementary analysis for the Formula: C^H^NC^ (309.37):Calculated [%] C: 73.77 H: 6.19 N: 4.53 0: 15.51 Found [%] C: 73.47 H: 6.24 N: 4.45IR (KBr): 3274, 3001, 2828, 2592, 2368, 1629, 1589, 1485, 1465, 1390, 1332 cm"1 -NMR (DMSO-d6, 400 MHz) delta 7.72 (dd, 1H, J = 7.7, 1.7 Hz), 7.57 (d, 1H, J = 7.4 Hz), 7.32 (m, 2H), 7.26 (m, 2H), 6.74 (d, 1H, J = 7.4 Hz), 6.71 (t, 1H, J = 8.8 Hz), 4.71 (dd, 1H, J = 7.4, 4.8 Hz), 3.85 (m, 2H), 3.54 (t, 1H, J = 2.4 Hz), 3.06 (m, 1H), 2.86 (m, 1H), 2.40 (m, lH), 2.15 (m, lH) ppm. HPLC purity: >99.8%[a] 22D = +16.4 (c=l ; EtOH)
	In ethyl acetate; acetone;Reflux;	Example 3Process for preparing Rasagiline Salicylate Crystalline Form I[0076] A mixture of acetone (20 ml) and salicylic acid (2.6 g) was heated to reflux temperature, followed by the addition of a solution of <strong>[136236-51-6]rasagiline</strong> base (3 g) dissolved in ethyl acetate (30 ml). The solvent was distilled completely under vacuum. Isopropyl alcohol (10) and diisopropyl ether (20 ml) were added to the resulting residue and stirred for 4 days. The separated solid was filtered, washed with chilled diisopropyl ether (5ml) and then dried in vacuum oven at 50 to 55C for 8 hours to yield 3.5 g of <strong>[136236-51-6]rasagiline</strong> salicylate crystalline Form I.

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 24-25
[2]Patent: WO2011/80589,2011,A2 .Location in patent: Page/Page column 14

58
[ 34698-41-4 ]
[ 136236-51-6 ]

Reference： [1]Patent: US2011/152381,2011,A1
[2]Patent: WO2012/153349,2012,A2
[3]Organic Process Research and Development,2014,vol. 18,p. 1169 - 1174
[4]Patent: WO2015/70995,2015,A1

59
(1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine L-(+)-tartrate [ No CAS ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; toluene; at 40 - 47℃;Industry scale; Inert atmosphere;	Step 2-Preparation of Rasagiline Base, 30 and 60 Liter Glass Lined Reactors with PTFE Piping, Hastelloy Filter-Dryer, Under Nitrogen Atmosphere25% NaOH solution (5.8 kg), deionized water (13.2 kg), dry Pure Rasagiline Tartrate (6.0 kg) prepared in Step 1 was introduced into 60 liter glass lined reactor. 13 kg of Toluene (13 kg) was added and the mixture was heated to 40 C. at stirring. After complete dissolution of solid the batch was stirred at 40-47 C. for 30 minutes then settled without stirring at the same temperature for phase separation.Lower aqueous phase was separated and discarded. Organic phase was washed in the reactor with 8 kg process water at 44-47 C.The batch was settled in reactor at 47-49 C. for 30 minutes and the lower aqueous phase was separated and discarded to waste, organic phase remained in the reactor.The solvent was distilled from the organic phase under vacuum, then 6.1 kg of ethanol were introduced into the reactor and the distillation was repeated.Residue of evaporation (Rasagiline base oil) was cooled to 19 C. and mixed with 2.6 kg of absolute ethanol. The solution was transferred through 0.2mu filter to 30 liter glass lined reactor. The line and the filter were washed with 1.9 kg absolute ethanol.Combined ethanolic solution and wash were cooled to 11 C. at stirring and 2 kg of process water added to the batch.Cooling was continued, crystallization of Rasagiline base started and batch was stirred at 11-12 C. for 1¼ hours. Then 8.5 kg of process water was added by portions during one hour.The batch was cooled to 6 C. and was held at this temperature for 30 minutes and then transferred to filter-dryer. The solid product was filtered under pressure of nitrogen and was washed twice with process water in nitrogen atmosphere.The cake was dried under vacuum at agitation and gentle heating (jacket temperature 35 C.) for 19 hours.Dry product-3.7 kg

Reference： [1]Patent: US2011/152381,2011,A1 .Location in patent: Page/Page column 9-10

60
[ 136236-51-6 ]
[ 161735-79-1 ]

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

61
[ 83-33-0 ]
[ 136236-51-6 ]

Reference： [1]Patent: US2011/218361,2011,A1
[2]Patent: WO2012/153349,2012,A2
[3]Organic Process Research and Development,2014,vol. 18,p. 1169 - 1174
[4]Applied Catalysis A: General,2015,vol. 492,p. 76 - 82
[5]Applied Catalysis A: General,2015,vol. 492,p. 76 - 82
[6]Applied Catalysis A: General,2015,vol. 492,p. 76 - 82
[7]Patent: WO2015/70995,2015,A1

62
[ 1227784-59-9 ]
[ 136236-51-6 ]

Reference： [1]Patent: US2011/218361,2011,A1

63
[ 1309125-23-2 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide;	Synthesis of Rasagiline 13.1 g of the compound (III) was alkalinized with 100 mL of sodium hydroxide (2%), and extracted with hexane for three times (100 mL each). The hexane layer was treated with sodium sulfate to remove water, filtered and concentrated, so as to obtain 6.2 g of rasagiline. The yield was 90%.

Reference： [1]Patent: US2011/218361,2011,A1 .Location in patent: Page/Page column 4

64
[ 136236-51-6 ]
[ 694436-33-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogen bromide; In isopropyl alcohol; at 5 - 10℃; for 0.5h;	Example 22 Preparation of <strong>[136236-51-6](1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine</strong> hydrobromide (Rasagiline hydrobromide): Rasagiline base (81 g, 0.47 moles) was dissolved in IPA (810 ml) under stirring to obtain a solution. The obtained solution was cooled to 5C. A solution of HBr in IPA (200 ml) was added dropwise to the cooled solution and stirred for 30 min at 5-10C. The obtained solid was filtered and dried to get (112 g, 90%) of the title compound.
	With hydrogen bromide; at 25 - 65℃; for 0.5h;Product distribution / selectivity;	Example-2:Preparation of (R)-<strong>[136236-51-6]rasagiline</strong> hydrobromide Form-I: bottom flask at 25C. 7.5 g of cone, hydrobromic acid was added and heated at 65C with stirring for 30 min. 60 mL methyl tert-butyl ether was added and stirred for 1 hour at 55C. The reaction mixture was cooled to 35C and filtered. The wet-cake was washed with mixture of methanol and methyl tert-butyl ether and dried for 12 hours at 55C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> hydrobromide. The product is characterized by XRD (FIG.5) and IR (FIG.6). The water content is less than 0.5%, which shows it is anhydrous. TGA (FIG.7)

Reference： [1]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 15
[2]Patent: WO2012/153349,2012,A2 .Location in patent: Page/Page column 25-26

65
[ 136236-51-6 ]
[ 1312753-57-3 ]
[ 1312753-56-2 ]

Yield	Reaction Conditions	Operation in experiment
15%; 15%		Example 23 : Preparation of N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (Impurity A) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide (Impurity B) (R)-Rasagiline base pure (30 g) was dissolved in HBr (250 ml) and the solution was heated to reflux for 36 h. After the completion of reaction the mixture was cooled, diluted with water (500 ml) and slowly the solution was basified using aqueous ammonia solution. The mixture was extracted with methyl tertiary butyl ether (MTBE). The separated MTBE layer was evaporated to get a dark brown oil which exhibited 3 spots on TLC, two of which were of the desired compounds i.e., N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (Impurity A) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide (Impurity B). The third spot had same Rf as that of the starting material i.e., the unreacted Rasagiline base. The products formed were separated by column chromatography (silica gel) using hexane-ethyl acetate mixture (75:25) as mobile phase to give pure N-2-Propene-1-yl-2-bromo-(R)-aminoindan (15% overall yield) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan (15% overall yield).
15%; 15%	With hydrogen bromide; for 36h;Reflux;	Example 23 Preparation of N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (Impurity A) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide (Impurity B) (R)-Rasagiline base pure (30 g) was dissolved in HBr (250 ml) and the solution was heated to reflux for 36 h. After the completion of reaction the mixture was cooled, diluted with water (500 ml) and slowly the solution was basified using aqueous ammonia solution. The mixture was extracted with methyl tertiary butyl ether (MTBE). The separated MTBE layer was evaporated to get a dark brown oil which exhibited 3 spots on TLC, two of which were of the desired compounds i.e., N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (Impurity A) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide (Impurity B). The third spot had same Rf as that of the starting material i.e., the unreacted Rasagiline base. The products formed were separated by column chromatography (silica gel) using hexane-ethyl acetate mixture (75:25) as mobile phase to give pure N-2-Propene-1-yl-2-bromo-(R)-aminoindan (15% overall yield) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan (15% overall yield). The obtained N-2-Propene-1-yl-2-bromo-(R)-aminoindan (5 g) in 100 ml of MTBE was added to 10 ml of 10% HBr/ IPA solution and the reaction mixture was stirred at 5-10 C. for 30 min. The precipitated solid was filtered, washed with MTBE and dried to give 8.7 g of N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (90% yield). Mass spectrum: [M+1]+: 252 (0157) N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide was synthesized by a similar process provided for synthesizing N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide. Mass spectrum: [M+1]+: 252

Reference： [1]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 15-16
[2]Patent: US8741962,2014,B2 .Location in patent: Page/Page column 20

66
[ 57-10-3 ]
[ 136236-51-6 ]
[ 1260684-23-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	In isopropyl alcohol; at 5 - 10℃; for 0.5h;	Example 24 : Preparation of <strong>[136236-51-6](1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine</strong> palmitate (Rasagiline palmitate): Rasagiline base (81 g, 0.47 moles) was dissolved in IPA (810 ml) under stirring to obtain a solution. The obtained solution was cooled to 5C. A solution of palmitic acid (0.49 moles, 125.6 g) in IPA (200 ml) was added dropwise to the cooled solution. After complete addition, the solution was stirred for 30 min at 5-10C. The obtained solid was filtered and dried to get (172 g, 85%) of the title compound.
85%	In isopropyl alcohol; at 5 - 10℃; for 0.5h;	Example 24 Preparation of <strong>[136236-51-6](1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine</strong> palmitate (Rasagiline Palmitate) Rasagiline base (81 g, 0.47 moles) was dissolved in IPA (810 ml) under stirring to obtain a solution. The obtained solution was cooled to 5 C. A solution of palmitic acid (0.49 moles, 125.6 g) in IPA (200 ml) was added dropwise to the cooled solution. After complete addition, the solution was stirred for 30 min at 5-10 C. The obtained solid was filtered and dried to get (172 g, 85%) of the title compound.

Reference： [1]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 16
[2]Patent: US8741962,2014,B2 .Location in patent: Page/Page column 20; 21

67
[ 6165-75-9 ]
(R)-2,3-dihydro-1H-inden-1-amine hydrochloride [ No CAS ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
65.8%	With sodium hydroxide; In toluene; at 30℃; for 29h;	Example 11 Preparation of rasagiline To a reactor 8.14 g of propargyl benzenesulphonate, 75.71 g of (R)- 1-aminoindan hydrochloride and 57 ml of toluene were added. The mixture was heated to 30°C, and then 18 ml of 15percent NaOH were slowly added, the mixture was further stirred at the same temperature for 29 hours . After completing the reaction 38.5 ml of water and 16 ml of toluene were added to the reaction mixture and stirred for 15 minutes, then the stirring was stopped and the phases were separated. The organic phase was washed with 38.5 ml of water and stirred for 15 minutes, then the phases were separated. The upper organic phase was washed with 38.5 ml of 10percent NaOH and stirred for 15 minutes, than the phases were separated. The organic phase was mixed with 23 ml of water and the pH was adjusted to 3.2 by addition of 12 ml of 10percent solution of H2S04. The phases were separated and the organic phase was discarded. To the water phase 38.5 ml of toluene were added and the pH was adjusted to 7.3 by adding 9 ml of 10percent NaOH. The phases were separated and the water phase was extracted twice by addition of 38.5 ml of toluene and adjusting pH to 7.3 by addition of 10percent solution of NaOH. Organic phases were collected and the solvent of the organic phase was evaporated under vacuum by heating and stirring. After the evaporation 4.87 g of an oily product with an assay of 74.9percent was obtained. Yield: 65.8percent, Enatiomeric purity: 99.96 area percent
65.8%	With sodium hydroxide; In toluene; at 30℃; for 29h;	To a reactor 8.14 g of propargyl benzenesulphonate, 75.71 g of (R) - 1-aminoindane hydrochloride and 57 ml of toluene were added. The mixture was heated to 30°C, and then 18 ml of 15percent NaOH were slowly added, the mixture was further stirred at the same temperature for 29 hours. After completion of the reaction 38.5 ml of water and 16 ml of toluene were added to the reaction mixture and stirred for 15 minutes, then the stirring was stopped and the phases were separated. The organic phase was washed with 38.5 ml of water and stirred for 15 minutes, then the phases were separated. The upper organic phase was washed with 38.5 ml of 10percent NaOH and stirred for 15 minutes, then the phases were separated. The organic phase was mixed with 23 ml of water and the pH was adjusted to 3.2 by addition of 12 ml of 10percent solution of H2SO4. The phases were separated and the organic phase was discarded. To the water phase 38.5 ml of toluene were added and the pH was adjusted to 7.3 by adding 9 ml of 10percent NaOH. The phases were separated and the water phase was extracted twice by addition of 38.5 ml of toluene and adjusting pH to 7.3 by addition of 10percent solution of NaOH. Organic phases were collected and the solvent of the organic phase was evaporated under vacuum by heating and stirring. After the evaporation 4.87 g of an oily product with an assay of 74.9percent was obtained . Yield: 65.8percent, Enantiomeric purity: 99.96 area percent
		Example 1Preparation of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine (Rasagiline base crude)900ml water was charged in a round bottom flask at room temperature followed by addition of NaOH pellets (70.5 g) and tetrabutyl ammonium bromide (6 g) under stirring.After completion of addition, the reaction mixture was cooled to 15-20°C. R-(-)-1-aminoindan hydrochloride (150 g) was charged and the mixture was stirred for 15 min followed by dropwise addition of propargyl benzenesulfonate (180 g) to the reaction mixture over a period of 45 min.The reaction mixture was stirred at 15-20°C for 2 hr.The reaction mass was checked on TLC for completion of reaction.1 L of toluene was charged to the reaction mass and stirred for 30 min.The toluene layer was separated and washed with 10percent aqueous NaOH solution.The aqueous layer was again extracted with 500 ml of toluene.The combined toluene layer was washed with water (2x500ml).250ml of water was added to the toluene layer and the mixture was cooled to 15-20°C followed by dropwise addition of 10percent aqueous sulfuric acid solution to attain pH 3.The toluene layer was separated and washed with 500 ml water.The combined aqueous layer was washed with toluene (2x 250 ml).The aqueous layer was cooled to 15-20°C and 10percent aqueous NaOH solution was added dropwise till pH 8.The reaction mixture was charged with 500 ml of toluene and stirred for 30 min.The toluene layer was separated and aqueous layer was extracted with 250 ml of toluene.The combined toluene layer was washed with (2x 500 ml) water.The separated toluene layer was dried over anhydrous sodium sulfate and distilled off under vacuum at 65°C to get (90 g, 60 percent) of the title compound as an oil.; Example 2: Purification of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine (Rasagiline base pure); Rasagiline base crude (dissolved in methylene dichloride) was purified by column chromatography using neutral alumina as a stationary phase and hexane-ethyl acetate (90:10) mixture as mobile phase to get (81.0 g, 90percent) of the title compound as an oil.; Example 3: Recovery of R(-)-aminoindan; The aqueous mother liquor obtained after separation of toluene layer (containing rasagiline base, Example 1) was basified to pH 12 using 10percent aq. NaOH (100 ml). 500 ml of toluene was charged to the above mixture and the reaction mass was stirred for 30 min. The toluene layer was separated and the aqueous layer was extracted with 250 ml of toluene. The combined toluene layers were washed with (2x 500 ml) water. The toluene layer was separated, dried over anhydrous sodium sulfate and distilled under vacuum at 65°C to get (15 g, 10 percent) of the title compound as an oil.

81.0 g

Example 1 Preparation of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine (Rasagiline Base Crude) 900 ml water was charged in a round bottom flask at room temperature followed by addition of NaOH pellets (70.5 g) and tetrabutyl ammonium bromide (6 g) under stirring. After completion of addition, the reaction mixture was cooled to 15-20° C. R-(-)-1-aminoindan hydrochloride (150 g) was charged and the mixture was stirred for 15 min followed by dropwise addition of propargyl benzenesulfonate (180 g) to the reaction mixture over a period of 45 min. The reaction mixture was stirred at 15-20° C. for 2 hr. The reaction mass was checked on TLC for completion of reaction. 1 L of toluene was charged to the reaction mass and stirred for 30 min. The toluene layer was separated and washed with 10percent aqueous NaOH solution. The aqueous layer was again extracted with 500 ml of toluene. The combined toluene layer was washed with water (2*500 ml). 250 ml of water was added to the toluene layer and the mixture was cooled to 15-20° C. followed by dropwise addition of 10percent aqueous sulfuric acid solution to attain pH 3. The toluene layer was separated and washed with 500 ml water. The combined aqueous layer was washed with toluene (2*250 ml). The aqueous layer was cooled to 15-20° C. and 10percent aqueous NaOH solution was added dropwise till pH 8. The reaction mixture was charged with 500 ml of toluene and stirred for 30 min. The toluene layer was separated and aqueous layer was extracted with 250 ml of toluene. The combined toluene layer was washed with (2*500 ml) water. The separated toluene layer was dried over anhydrous sodium sulfate and distilled off under vacuum at 65° C. to get (90 g, 60percent) of the title compound as an oil.Example 2 Purification of (1R)-2,3-dihydro-N-2-propynyl-1H-indane-1-amine (Rasagiline Base Pure) (0132) Rasagiline base crude (dissolved in methylene dichloride) was purified by column chromatography using neutral alumina as a stationary phase and hexane-ethyl acetate (90:10) mixture as mobile phase to get (81.0 g, 90percent) of the title compound as an oil.

Reference： [1]Patent: WO2015/70995,2015,A1 .Location in patent: Page/Page column 26
[2]Patent: WO2016/116607,2016,A1 .Location in patent: Page/Page column 31-32
[3]Patent: EP2364967,2011,A2 .Location in patent: Page/Page column 12-13
[4]Patent: US8741962,2014,B2 .Location in patent: Page/Page column 16

68
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; In methanol; at 25 - 65℃; for 0.5h;	5 g or (R)-(+)-iasagiline base and 15 mL methanol were taken in round bottom flask at 25C. 7.5 g of cone, hydrobromic acid was added and heated at 65C with stirring for 30 min.60 mL methyl tert-butyl ether was added and stirred for 1 hour at 55C. The reaction mixture was cooled to 35C and filtered. The wet-cake was washed with mixture of methanol and methyl tert-butyl ether and dried for 12 hours at 55C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> hydrobromide. The product is characterized by XRD (FIG.l) and IR (FIG.2). The water content is less than 0.5%, which shows it is anhydrous. TGA (FIG.3)

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 24

69
[ 120-18-3 ]
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan 2-napsylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 25 - 55℃; for 0.5h;	10 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 100 mL acetone were taken in round bottom flask at 25C. 12.14 g of naphthalene-2-sulphonic acid was added and heated at 55C with stirring for 30 mins. The reaction mixture was cooled to 25C-35C and stirred for 1 hour. The product was filtered and washed with acetone. The product was dried for 12 hours at 45C under vacuum to obtain crystalline (R)-<strong>[136236-51-6]rasagiline</strong> 2-napsylate. The product is characterized by XRD (FIG.l 1 ) and DSC (FIG.12).

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 26

70
[ 81-04-9 ]
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan 1,5-dinapsylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 25 - 55℃; for 0.5h;Product distribution / selectivity;	10 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 100 mL acetone were taken in round bottom flask at 25C. 16.8 g of naphthalene- 1,5-disulphonic acid was added and heated at 55C with stirring for 30 mins. The reaction mixture was cooled to 25C-35C and stirred for 1 hour. The product was filtered and washed with acetone. The product was dried for 12 hours at 45C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> 1,5- dinapsylate. The product is characterized by XRD (FIG.13) and DSC (FIG.14).

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 26

71
[ 110-04-3 ]
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan 1,2-edisylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 25 - 55℃; for 0.5h;	10 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 100 mL acetone were taken in round bottom flask at 25C. 1 1.08 g of ethane- 1,2-disulphonic acid was added and heated at 55C with stirring for 30 mins. The reaction mixture was cooled to 25C-35C and stirred for 1 hours. The product was filtered and washed with acetone. The product was dried for 12 hours at 45C under vacuum to obtain crystalline Form-II of (R)-<strong>[136236-51-6]rasagiline</strong> 1 ,2- edisylate. The product is characterized by XRD (FIG.9) and DSC (FIG.10).

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 25-26

72
[ 78619-96-2 ]
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan ascorbate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 25 - 65℃; for 0.5h;	10 g or (R)-(+)-<strong>[136236-51-6]rasagiline</strong> freebase and 20 mL methanol were taken in round bottom flask at 25C. 10.3 g ascorbic acid was added and heated at 65C with stirring for 30 min. 60 mL methyl tert-butyl ether was added and stirred for 1 hour at 55C. The reaction mixture was cooled to 35C and filtered. The wet-cake was washed with mixture of methanol and methyl tert-butyl ether and dried for 12 hours at 55C under vacuum to obtain 15 g crystalline (R)-<strong>[136236-51-6]rasagiline</strong> ascorbate

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 27

73
[ 85-47-2 ]
[ 136236-51-6 ]
R-(+)-N-propargyl-1-aminoindan 1-napsylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 25 - 55℃; for 0.5h;	10 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 100 mL acetone were taken in round bottom flask at 25C. 12.14 g of naphthalene- l -sulphonic acid was added and heated at 55C with stirring for 30 mins. The reaction mixture was cooled to 0C-5C and stirred for 1 hour. The product was filtered and washed with chilled acetone. The product was dried for 12 hours at 45C under vacuum to obtain crystalline (R)-<strong>[136236-51-6]rasagiline</strong> 1 -napsylate. The product is characterized by XRD (FIG.17) and DSC (FIG.18).

Reference： [1]Patent: WO2011/121607,2011,A2 .Location in patent: Page/Page column 26-27

74
[ 97-67-6 ]
[ 136236-51-6 ]
[ 1377248-96-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	In methanol; for 1h;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base and 391 mg (2.915 mmoles) of ( )-malic acid are dissolved in 1.0 ml of methanol. The solution is stirred for an hour, evaporated to dryness in vacuo and the residue is treated with a mixture of isopropyl-alcohol and diisopropyl ether. The solid substance is filtered off, washed with the above solvent mixture and dried on the air.Yield: 706 mg (79 %), off-white crystals.Melting point: 83-89 CElementary analysis for the Formula: C16H19N05 (305,33):Calculated [%] C: 62.94 H: 6.27 N: 4.59 0: 26.20 Found [%] C: 62.68 H: 6.23 N: 4.47IR (KBr): 3357, 3232, 2953, 2819, 1695, 1563, 1462, 1282, 1167, 1085 cm"1.1H-NMR (DMSO-<¾, 400 MHz) delta 7.41 (d, 1H), 7.26 (m, 1H), 7.23(m, 1H), 7.20 (m, 1H), 4.43 (m, 1H), 4.13 (t, 1H, J = 6.3 Hz), 3.58 (m, 2H), 3.28 (m, 1H), 2.98 (m, 1H), 2.78 (m, 1H), 2.57 (dd, 1H, J = 15.6, 6.5 Hz), 2.40 (dd, 1H, 15.6, 6.2 Hz), 2.32 (m, 1H), 1.91 (m, 1H) ppm.HPLC purity: >99,8%[a] 22D = +20,8 (c=l ; EtOH)

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 34

75
[ 79-14-1 ]
[ 136236-51-6 ]
[ 1377248-94-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	In methanol; at 20℃; for 1h;	500 mg (2.920 mmol) of <strong>[136236-51-6]rasagiline</strong> base are dissolved in 1.5 ml of methanol, whereupon 220 mg (2.920 mmol) of hydroxyacetic acid are added. The solution is stirred at room temperature for an hour. The solvent is removed in vacuo and the residue is crystallized from a mixture of isopropyl alcohol and diisopropyl ether. The crystals are filtered, washed with cold diisopropyl ether and air-dried at room temperature.Yield: 452 mg (62 %), off-white crystalsMelting point: 78.0-79.5 CElementary analysis for the Formula C14Hj7N03 (247.30):Calculated [%] C: 68.00 H: 6.93 N: 5.66 O: 19.41 Found [%] C: 67.82 H: 6.86 N: 5.55IR (KBr): 3333, 3276, 2916, 1630, 1550, 1460, 1400, 1314,1082 cm"1. '1H-NMR (DMSO- , 400 MHz): delta 7.35 (m, 1H), 7.22 (m, 1H), 7.18 (m, 1H), 7.16 (m, 1H), 4.30 (m, 1H), 3.87 (m, 2H), 3.43 (s, 2H), 3.11 (m, 1H), 2.93 (m, 1H), 2.74 (m, 1H), 2.22 (m, 1H), 1.79 (m, 1H) ppm. HPLC purity: >99.8 %[a] 22D = +20,0 (c=l; EtOH)

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 16

76
[ 636-61-3 ]
[ 136236-51-6 ]
[ 1377248-97-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	In isopropyl alcohol;Heating; Cooling with ice;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base and 391.5 (2.920 mmoles) of (Z))-malic acid are dissolved in 5.0 ml of hot isopropyl-alcohol. The warm solution is slowly cooled and thereafter placed in an icecold water bath. The precipitated crystals are filtered and washed with cold isopropyl-alcohol; The off-white crude salt thus obtained (830 mg) is recrystallized from 1 1 ml of hot isopropyl-alcohol, filtered in the cold, washed with cooled isopropyl-alcohol and finally dried on the air. Yield : 745 mg (84 %), white crystals.Melting point: 126-129 CElementary analysis for the Formula: Ci6Hi9N0 (305,33): CAlculated [%] C: 62.94 H: 6.27 N: 4.59 O: 26.20 Found [%] C: 62.62 H: 6.40 N: 4.47IR (ICBr): 3222, 2965, 2588, 2454, 1708, 1631, 1561 , 1412, 1311, 1276, 1216, 1183, 1091 cm"1.1H-NMR (DMSO- 6, 400 MHz) delta 8.41 (bs, 4H), 7.41 (d, 1H, J = 7.1 Hz), 7.26 (t, 1H, J = 7.0 Hz), 7.23 (d, 1H, J = 7.2 Hz), 7.20 (t, 1H, J = 7.0 Hz), 4.44 (dd, 1H, J = 6.8, 5.8 Hz), 4.13 (t, 1H, J = 6.6 Hz), 3.58 (d, 2H, J = 2.5 Hz), 3.28 (t, 1H, J = 2.5 Hz), 2.98 (m, 1H), 2.80 (m, 1H), 2.57 (dd, lH, J = 15.6, 6.6 Hz), 2.39 (dd, 1H, J = 15.6, 6.5 Hz), 2.33 (m, 1H), 1.90 (m, 1H) ppm.HPLC purity: >99.8%[a] 22D = +14,l (c=l; EtOH)

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 36-37

77
[ 81-04-9 ]
[ 136236-51-6 ]
di(rasagiline) naphthalene-1,5-disulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In isopropyl alcohol; at 20℃;Cooling with ice;	500 mg (2.920 mmoles) of <strong>[136236-51-6]rasagiline</strong> base are dissolved in 3.0 ml of isopropyl alcohol at room temperature whereupon a solution of 1053 mg (2.922 mmoles) of naphthalene-l,5-disulfonic acid-tetrahydrate in 4.0 ml of isopropyl alcohol is added. The solution is mixed and cooled in an icecold water-bath. The precipitated crystals are filtered, washed with cold isopropyl alcohol and air-dried.Yield: 790 mg (86 %), white crystals Melting point: 204-220 CElementary analysis for the Formula: C34H34N206S2 (630.79):Calculated [%] C: 64.74 H: 5.43 N: 4.44 S: 10.17 0: 15.22 Found [%] C: 64.30 H: 5.62 N: 4.37 S: 10.36IR (KBr): 3245, 2985, 2816, 1596, 1454, 1219, 1150, 1027 cm"1. 1H-NMR (DMSO-i/6, 400 MHz) delta 8.87 (d, 2H, J = 8.7 Hz), 7.93 (dd, 2H, J = 7.1, 1.0 Hz), 7.59 (d, 2H, J = 7.6 Hz), 7.40 (dd, 2H, J = 8.5, 7.2 Hz), 7.38 (m, 2H), 7.37 (m, 2H), 7.31 (t, 2H), 4.81 (m, 2H), 4.00 (m, 4H), 3.77 (t, 2H, J = 2.5 Hz), 3.09 (m, 2H), 2.88 (m, 2H), 2.43 (m, 2H), 2.18 (m, 2H) ppm.HPLC purity: >99.8%[ ] 22D = +15.0 (c=l ; EtOH)

Reference： [1]Patent: WO2012/66366,2012,A1 .Location in patent: Page/Page column 26-27

78
[ 155666-94-7 ]
[ 136236-51-6 ]

Reference： [1]Patent: WO2012/96635,2012,A1
[2]Patent: US2014/18578,2014,A1

79
(R)-2,3-dihydro-1H-inden-1-amine hydrochloride [ No CAS ]
[ 136236-51-6 ]

Reference： [1]Patent: WO2012/96635,2012,A1

80
[ 1378030-60-4 ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In methanol; water; at 30 - 35℃;	2. HydrolysisYellowish-red oil from step 1 was dissolved in MeOH (140 mL) and 20% KOH solution (58 mL) was added to obtain a homogeneous solution. Reaction mixture was stirred at 30-35 C until completion of the starting material as indicated by TLC and HPLC. After the completion of the reaction (>99.9 conversion after 30 min, purity >99.5%), MeOH was evaporated and the aqueous phase was extracted with MTBE. Combined organic phases were dried over MgS04 and filtered to obtain a bright yellow solution which was evaporated to dryness in a rotary evaporator, afforded Formula 1 as an oil (14.3 g, >99.5 HPLC purity).
14.3 g	With water; potassium hydroxide; In methanol; at 30 - 35℃; for 0.5h;	Yellowish-red oil from step 1 was dissolved in MeOH (140 mL) and 20% KOH solution (58 mL) was added to obtain a homogeneous solution. Reaction mixture was stirred at 30-35 C. until completion of the starting material as indicated by TLC and HPLC. After the completion of the reaction (>99.9 conversion after 30 min, purity >99.5%), MeOH was evaporated and the aqueous phase was extracted with MTBE. Combined organic phases were dried over MgSO4 and filtered to obtain a bright yellow solution which was evaporated to dryness in a rotary evaporator, afforded Formula 1 as an oil (14.3 g, >99.5 HPLC purity).

Reference： [1]Patent: WO2012/96635,2012,A1 .Location in patent: Page/Page column 7
[2]Patent: US2014/18578,2014,A1 .Location in patent: Paragraph 0028-0029

81
[ 1875-50-9 ]
[ 136236-51-6 ]

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

82
[ 136236-51-6 ]
[ 1204184-73-5 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphoric acid; In isopropyl alcohol; at 25 - 40℃; for 2h;	Example-5:Preparation of (R)-Rasagiline hydrogen phosphate Form-I3 g of (R)-(+)-<strong>[136236-51-6]rasagiline</strong> base and 20 mL isopropanol were taken in round bottom flask at 25C. 0.5 g of phosphoric acid was added and heated at 40C with stirring for 1 hours. The reaction mixture was cooled to 25C and stirred for 1 hour. The stirring RPM (rotation per minute) should be in the range of 60 to 100 and cooling rate should be 5C/hour. The reaction mixture was maintained overnight and filtered. The product was filtered and washed with isopropanol. The product was dried for 12 hours at 55C under vacuum to obtain crystalline Form-I of (R)-<strong>[136236-51-6]rasagiline</strong> phosphate. The product was characterized by XRD (FIG.9) and IR (FIG.10).Rasagiline hydrogen phosphate samples PSD were measured using MalvernLaser diffraction, using the Malvern Mastersizer 2000 instrument by the method disclosed in example-2. The crystalline <strong>[136236-51-6]rasagiline</strong> hydrogen phosphate may have particle size distributions, wherein the 10th volume percentile particle size (D10) is greater than about 20 um, the 50th volume percentile particle size (D5o) is greater than about 100 mu?iota, or the 90th volume percentile particle size (D90) is greater than about 250 um, or any combination thereof.

Reference： [1]Patent: WO2012/153349,2012,A2 .Location in patent: Page/Page column 28

83
[ 68253-35-0 ]
[ 136236-51-6 ]

Reference： [1]Patent: WO2012/153349,2012,A2
[2]Organic Process Research and Development,2014,vol. 18,p. 1169 - 1174
[3]Patent: WO2015/70995,2015,A1

84
[ 64-18-6 ]
[ 136236-51-6 ]
[ 1429316-88-0 ]

Yield	Reaction Conditions	Operation in experiment
12.0 g	With acetic anhydride; at 0 - 20℃; for 21h;	Example 1 Preparation of R(+)-N formyl-propargyl-aminoindan 15.4 g (0.09 mole) of <strong>[136236-51-6]rasagiline</strong> base (R-(+)-N-Propargyl-aminoindan) was added to a mixture of acetic anhydride (11.4 ml, 0.12 mole) and formic acid (5.7 ml, 0.15 mole) at stirring by portions over 15 min. at cooling. The mixture was stirred at 0-5 C. for hr and then at room temperature for 20 hrs. Reaction mixture was evaporated to dryness under vacuum. The residual oil was dissolved in ethylacetate and transferred to a chromatographic column. Chromatographic isolation: Column 120.0 g, mobile phase EtOAc:Hexane 30:70. Isolated fraction from the chromatographic column containing R(+)-N-formyl-propargyl-aminoindan was evaporated. The residue (15.2 g of oil) was dissolved in 250 ml EtOAc and washed with water, 10% NaHCO3 and brine. Organic solution was dried over Na2SO4 and evaporated. The residue (oil) was dried under high vacuum (2 mbar). Yield-12.0 g of yellowish oil.

Reference： [1]Patent: US2013/89612,2013,A1 .Location in patent: Paragraph 0107-0112

85
C₈H₁₁ClO₆ [ No CAS ]
[ 136236-51-6 ]
[ 1429321-79-8 ]

Yield	Reaction Conditions	Operation in experiment
1.8 g	With triethylamine; In dichloromethane; at 0 - 20℃; for 2.75h;	3. Preparation of 1-Rasagiline-2,3-dimethyl Citramide 1,2-Dimethyl citrate (5.4 g, 24.5 mmol) was dissolved in DCM (100 ml) and thionyl chloride (3.8 g, 32 mmol) was carefully added at RT. The resulted clear solution was stirred for 2 hr at RT and evaporated to dryness. The colorless residue was dissolved in DCM (50 ml) and was then added to a mixture of PAI (8.4 g, 50 mmol) and triethylamine (3.7 g, 37 mmol) in DCM (100 ml) for 15 min at 0-5 C. followed by stirring for 0.5 hr at 0-5 C. and 2 hr at R.T. The reaction mixture was then washed with 1N HCl and water, the organic solution was dried over sodium sulfate and evaporated to dryness to yield 2.9 g of green solid that was purified by column chromatography (20% ethyl acetate in hexane). 1.8 g (20%) of colorless solid was obtained.

Reference： [1]Patent: US2013/89611,2013,A1 .Location in patent: Paragraph 0133; 0138; 0139

86
[ 77-92-9 ]
[ 136236-51-6 ]
[ 1429321-78-7 ]

Yield	Reaction Conditions	Operation in experiment
0.22 g	In water; at 80℃; for 24h;Inert atmosphere;	Citric acid (60.0 g), <strong>[136236-51-6]rasagiline</strong> base (30.0 g) and water (10 ml) were heated under argon at 80 C. for 24 hr. The resulting oil was dissolved in water (300 ml) and 1N HCl (pH=1-2) was added. The reaction mixture was extracted by ethyl acetate (4×100 ml), the ethyl acetate extract was dried over sodium sulfate and evaporated to dryness. The resulting green oily residue (1.0 g) was purified by column chromatography (2% methanol in DCM) to give 0.22 g of a yellow solid.

Reference： [1]Patent: US2013/89611,2013,A1 .Location in patent: Paragraph 0125-0127

87
[ 106-96-7 ]
(R)-2,3-dihydro-1H-inden-1-amine hydrochloride [ No CAS ]
[ 136236-51-6 ]

Yield	Reaction Conditions	Operation in experiment
22 g		Example-l-Preparation of R(+) N propargyl amino indane Acetonitrile (700.00ml), R (-) Aminoindan HC1 (50.00g) and Potassium carbonate (80. lg) were charged to a reactor provided with the CaC^ (fused) guard tube and the reaction mass was heated to 60-62 deg C under stirring for 1 hr.Propargyl chloride (17.0 g) was added to the mass dropwise and the reaction mass maintained for 28 hrs. A sample of the rcn mass was analysed after 28 hrs.Acetonitrile was distilled off at 60-65 deg C under 200 mbar vacuum.The RM was cooled to 25-30 deg C, Water (510ml) was added to the residue and stirred for 20 mins. The aqueous reaction mass was then extracted with Dichloromethane (1x383ml; 1x125 ml) & the DCM. layer separated. 500 ml DM water was added to the combined Dichloromethane layer and the pH adjusted to 2.0-2.5 by adding 55ml (1 :1 cone. HC1: DM water). The DCM layer was separated while the aq. Layer was extracted with DCM (3 X 500ml) and DCM layers discarded. The pH of aq. Layer was adjusted to 4.5-5.0 by addition of 40 ml of 50% aq. potassium carbonate solution. The aq. Layer was extracted with DCM (3x500ml). 500ml DM water was added to the combined DCM layers and a pH= 10.5- 11.0 was adjusted using 25ml of 50% aq. Potassium carbonate solution. DCM layer was separated and distilled out under vacuum to provide an Oily mass. Yield data: Rasagiline free base: 22.0 g Purity: 99.82%

Reference： [1]Patent: WO2013/54346,2013,A2 .Location in patent: Page/Page column 12

88
[ 1875-50-9 ]
[ 136236-51-6 ]
N-Propargyl-1(S)-aminoindan [ No CAS ]

Reference： [1]Chirality,2013,vol. 25,p. 324 - 327

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	136236-51-6	MDL No. :	MFCD00866571
Formula :	C₁₂H₁₃N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RUOKEQAAGRXIBM-GFCCVEGCSA-N
M.W :	171.24	Pubchem ID :	3052776
Synonyms :	(R)-AGN1135;TVP1012;Azilect, HSDB 7699, Rasagiline, TV 1030, TV-1030;(R)-(+)-Rasagiline

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.33
Num. rotatable bonds :	2
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	54.45
TPSA :	12.03 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.05 cm/s

Log Po/w (iLOGP) :	2.51
Log Po/w (XLOGP3) :	1.83
Log Po/w (WLOGP) :	1.65
Log Po/w (MLOGP) :	2.58
Log Po/w (SILICOS-IT) :	2.85
Consensus Log Po/w :	2.28

[ CAS No. 136236-51-6 ] {[proInfo.proName]}

Quality Control of [ 136236-51-6 ]

Related Doc. of [ 136236-51-6 ]

Product Details of [ 136236-51-6 ]

Calculated chemistry of [ 136236-51-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 136236-51-6 ]

Application In Synthesis of [ 136236-51-6 ]

[ 136236-51-6 ] Synthesis Path-Downstream 1~88

Similar Product of
[ 136236-51-6 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.26
Solubility :	0.932 mg/ml ; 0.00544 mol/l
Class :	Soluble
Log S (Ali) :	-1.7
Solubility :	3.39 mg/ml ; 0.0198 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.53
Solubility :	0.0505 mg/ml ; 0.000295 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.13

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	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
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
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. 136236-51-6 ] {[proInfo.proName]}

Quality Control of [ 136236-51-6 ]

Related Doc. of [ 136236-51-6 ]

Product Details of [ 136236-51-6 ]

Calculated chemistry of [ 136236-51-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 136236-51-6 ]

Application In Synthesis of [ 136236-51-6 ]

[ 136236-51-6 ] Synthesis Path-Downstream 1~88

Similar Product of [ 136236-51-6 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Similar Product of
[ 136236-51-6 ]