Home Cart 0 Sign in  

[ CAS No. 104632-25-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 104632-25-9
Chemical Structure| 104632-25-9
Structure of 104632-25-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 104632-25-9 ]

Related Doc. of [ 104632-25-9 ]

Alternatived Products of [ 104632-25-9 ]

Product Details of [ 104632-25-9 ]

CAS No. :104632-25-9 MDL No. :MFCD00876894
Formula : C10H19Cl2N3S Boiling Point : -
Linear Structure Formula :- InChI Key :QMNWXHSYPXQFSK-KLXURFKVSA-N
M.W : 284.25 Pubchem ID :119569
Synonyms :
(S)-Pramipexole (hydrochloride);SND919;(–)-Pramipexole

Calculated chemistry of [ 104632-25-9 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.7
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 75.1
TPSA : 79.18 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -5.58 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 3.46
Log Po/w (WLOGP) : 3.19
Log Po/w (MLOGP) : 1.59
Log Po/w (SILICOS-IT) : 2.64
Consensus Log Po/w : 2.18

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.82
Solubility : 0.0435 mg/ml ; 0.000153 mol/l
Class : Soluble
Log S (Ali) : -4.8
Solubility : 0.00446 mg/ml ; 0.0000157 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.07
Solubility : 0.242 mg/ml ; 0.000853 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.51

Safety of [ 104632-25-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P273-P301+P312+P330-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H412 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 104632-25-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 104632-25-9 ]
  • Downstream synthetic route of [ 104632-25-9 ]

[ 104632-25-9 ] Synthesis Path-Upstream   1~18

  • 1
  • [ 104632-25-9 ]
  • [ 104632-26-0 ]
YieldReaction ConditionsOperation in experiment
86% With potassium hydroxide In water at 20℃; for 1 - 2 h; Example 4; A 100 ml reaction vessel equipped with a magnetic stirrer was charged with 5.0 g of S-Pramipexole dihydrochloride and 37 ml of water. 2 ml of 30percent aqueous hydrogen peroxide solution were added and the reaction mixture was stirred at room temperature. After 1 hour 13 ml of 45percent potassium hydroxide solution were added in portions and the suspension was stirred at room temperature for 1 hour. The precipitate was filtered, washed with cold water and dried at 60° C. under vacuum to yield 3.0 g (86percent) of S-Pramipexole base.; Example 5; A 50 ml reaction vessel equipped with a magnetic stirrer was charged with 2.15 g of S-Pramipexole dihydrochloride and 16 ml of water. 5.6 ml of 45percent potassium hydroxide solution were added in portions and the suspension was stirred at room temperature for 1 hour. The precipitate was filtered, washed with cold water and dried at 60° C. under vacuum to yield 1.3 g (86percent) of Pramipexole base.
Reference: [1] Patent: US2006/69263, 2006, A1, . Location in patent: Page/Page column 4
[2] Patent: WO2005/14562, 2005, A1, . Location in patent: Page/Page column 15
  • 2
  • [ 106006-84-2 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
78.2%
Stage #1: With potassium borohydride; triethylamine; lithium chloride In tetrahydrofuran at 20℃; for 7 h; Inert atmosphere; Reflux
Stage #2: at -5 - 20℃; for 5 h; Reflux
The synthesis method 3 specifically comprises the following steps: (1) Under an atmosphere of nitrogen, 74.8 g of anhydrous lithium chloride was dissolved in 800 ml of anhydrous tetrahydrofuran, and 53.94 g of potassium borohydride and 50 g of triethylamine were added thereto. (2) The mixture was stirred at room temperature for 2 hours. Then, 112.5 g of the intermediate (S) -2-amino-6-propionamido-4,5,6,7-tetrahydrobenzothiazole was added, and the temperature was raised to reflux, After refluxing for 5 hours, the reaction was followed up to the end by TLC. (3) The system was cooled to -5 ° C and 125 g of concentrated hydrochloric acid was added. (4) After stirring at room temperature for 1h, the temperature was raised to reflux, and reflux was maintained for 4 hours. After the system was cooled to room temperature, the pH was adjusted to 9-10 with 30percent potassium carbonate aqueous solution and stirred for 1 hour. The separated aqueous phase was reextracted once with 200 ml of tetrahydrofuran. The organic phase was combined, washed with saturated brine, Dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give an off-white solid which was recrystallized from 1 L of ethyl acetate to give 82.3 g of a white solid in 78.2percent yield.
72%
Stage #1: With chloro-trimethyl-silane In dichloromethane at 0 - 15℃; Inert atmosphere
Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran; dichloromethane at -10 - 0℃; Inert atmosphere
General procedure: In typical experimental procedure for the Synthesis of (3aS,12bS)-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrolemaleate(1b’): Amide (1a) (10 g, 33.43 mmol) and DCM (100 mL) were charged into a round bottomed flask and stirred under nitrogen atmosphere for 10-15 minutes and cooled to 0-5°C. Trimethylsilyl chloride (5.1 mL, 40.12 mmol) was then added to the mixture over 10-15 minutes and stirred for 10-15 minutes at same temperature.Lithium aluminum hydride (19.5 mL, 46.81 mmol) in THF solution is added dropwise at -10-0°C. After complete addition, the solution is allowed to 0-10°C and stirring is continued for 1-2 hours. After completion of reaction (TLC), thereaction was quenched by slow dropwise addition of 2M sodium hydroxide (30 mL)and stirred for 10-15 minutes. Separate aqueous and organic layer. Extract the compound from aqueous layer with DCM (50.0 mL). Combine both the organic layerand wash with 20percent sodium chloride solution. Concentrate the DCM to get the crude which was dissolved in isopropyl alcohol (50.0 mL).
Reference: [1] Patent: CN105936629, 2016, A, . Location in patent: Paragraph 0057; 0058; 0059; 0060; 0061; 0062
[2] Tetrahedron Letters, 2013, vol. 54, # 36, p. 4908 - 4913
[3] Patent: WO2011/21214, 2011, A2,
[4] Patent: CN104496936, 2017, B, . Location in patent: Paragraph 0024; 0030-0033; 0041; 0043; 0051; 0053
  • 3
  • [ 943319-02-6 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
86% With acetyl chloride In isopropyl alcohol at 5 - 20℃; for 12.5 h; b) Direct methodTo the solution of acetyl chloride (21.4 g, 0.26 mole) in propan-2-ol (20 mL) pramipexole p-toluenesulfonate (3 g, 0.008 mole) was added portionwise. The resulting mixture was stirred for 0.5 h at room temp., than for 12 h at 50C. White, crystalline solid of pramipexole dihydrochloride was formed, which was filtered off, it was obtained 1.9 g (86 percent) of the product, m.p. 297-2980C.
78%
Stage #1: With hydrogenchloride In water at 0℃; for 0.25 h;
Stage #2: With sodium hydroxide In water at 0℃; for 3 h;
The p-toluenesulfonic acid salt of (S)-pramipexole 1 was prepared in 54percent yield, according to the literature,27 by reaction of diamine (S)-2 with n-propyl tosylate 15, which was also prepared according to the literature.32 1H NMR (CD3OD): δ 7.72 (2H, d, J=8.0Hz, 2′ and 6′), 7.25 (2H, d, J=8.0Hz, 3′ and 5′), 3.55 (1H, dddd, J=11.6, 8.8, 5.3, 2.90Hz, 6-H), 3.09–3.05 (3H, m, 7a-H and CH2CH2CH3), 2.71–2.60 (3H, m, 4a-H, 4b-H and 7b-H), 2.39 (3H, s, PhCH3), 2.27 (1H, m, 5a-H), 1.93 (1H, dddd, J=12.9, 10.6, 9.6, 6.2Hz, 5b-H), 1.75 (2H, tq, J=8.0, 7.4Hz, CH2CH2CH3), 1.06 (3H, t, J=7.4Hz, CH2CH2CH3). (S)-Pramipexole p-toluenesulfonic salt (0.350 g, 0.914 mmol) was suspended in water (1.5 mL) and, after cooling at 0°C, 12 M hydrogen chloride aqueous solution (76 μL) was added. The mixture was kept under stirring for 15 min. after which 1 M sodium hydroxide aqueous solution (0.914 mL) was added while keeping the temperature at 0°C over 3 h. The precipitate pramipexole 1 was recovered by filtration and following the reported method,27 was transformed into the corresponding dihydrochloride monohydrate (0.245 g, 78percent). The ee was established by HPLC analysis (Chiralpak IA, hexane/ethanol/diethylamine 70:30:0.1) Rt (R)-isomer 5.53min; (S)-isomer 7.39min. 1H NMR (CD3OD): δ 3.69 (1H, dddd, J=11.4, 8.6, 5.3, 3.0Hz, 6-H), 3.17 (1H, dd, J=16.0, 6.2Hz, 7a-H), 3.12 (2H, t, J=8.0Hz, CH2CH2CH3), 2.85–2.72 (3H, m, 4a-H, 4b-H and 7b-H), 2.41 (1H, dddd, J=13.9, 5.3, 3.0, 1.4Hz, 5a-H), 2.08 (1H, dddd, J=13.9, 8.6, 6.3, 2.4Hz, 5b-H), 1.82 (2H, tq, J=8.0, 7.4Hz, CH2CH2CH3), 1.08 (3H, t, J=7.4Hz, CH2CH2CH3). 13C NMR (CD3OD): δ 170.1 (2-C), 133.0 (N-C), 111.6 (S-C), 53.2 (6-C), 46.9 (CH2CH2CH3), 24.9 (7-C), 23.9 (5-C), 20.6 (4-C), 19.5 (CH2CH2CH3), 9.9 (CH2CH2CH3).
Reference: [1] Patent: WO2007/75095, 2007, A1, . Location in patent: Page/Page column 7
[2] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
  • 4
  • [ 1265141-51-2 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
85% With hydrogenchloride In tetrahydrofuran at 20 - 25℃; for 12 h; 20 g of formula III (S)-t-butyl-2-amino-4,5,6,7-tetrahydrobenzo[d] thiazol6yl(propyl) carbamate 5ml of conc. HCl was dissolved in 50ml of THF and stirred for 12 hours at 20 to 25 ° C. The resulting solid was filtered dried to give the pramipexole 16.5g (85percent yield) of the general formula I.
Reference: [1] Patent: KR101546713, 2015, B1, . Location in patent: Paragraph 0075; 0076
  • 5
  • [ 104632-26-0 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogenchloride In water; acetone at 0 - 3℃; for 2 h; Example 8
(S)-2-Amino-6-(n-propyl)amino-4,5,6,7-tetrahydrobenzothiazole dihydrochloride monohydrate, (S)-pramipexole dihydrochloride monohydrate (I*2 HCl*1 H2O)
A solution of (S)-pramipexole free base (Ia) (24.30 g) in acetone (730 ml) was cooled to 0-3°C, its pH was adjusted to 1.5 by the addition of 37percent hydrochloric acid.
The mixture was stirred at that temperature for 2 h and the precipitated crystals were collected by filtration.
The cake was washed with cold acetone and air-dried to give 34.16 g (98percent) product with m.p. 278-280°C. HPLC (purity, Apercent): 99.95percent, [α]D20: -67.3 (c = 1.0, MeOH), optical purity (Apercent) (HPLC, using a chiral, optically active stationary phase): 99.6percent ee.
95.8% With hydrogenchloride In water; isopropyl alcohol at 20℃; for 2 h; S-(-) pramipexole II (47.3 mmol, 10 g) and 100 mL of isopropanol were added, dissolved under stirring, and 8.5 mL of concentrated hydrochloric acid was added dropwise.After the addition was completed, the reaction was performed at room temperature for 2 hours.After the reaction was completed, the mixture was suction-filtered and dried to obtain 13.7 g of a white solid. The yield was 95.8percent, chemical purity was 100percent, and the optical purity was 100percent.
89% With hydrogenchloride In ethanol; isopropyl alcohol at 5 - 20℃; for 2 h; Example 6 A 50 ml reaction vessel equipped with a magnetic stirrer was charged with 2.53 g of S-Pramipexole base and 20 ml of absolute ethanol. The reaction mixture was stirred at room temperature to afford a clear solution. The reaction mixture was filtered and the filtrate was transferred to a 50 ml reaction vessel. 7.8 ml of 14.6percent solution of HCl in isopropanol were added in portions and the resulting reaction mixture was stirred for 1 hour. The mixture was cooled to 5° C. and stirred for additional 1 hour. The precipitate was filtered, washed with cold ethanol and dried at 60° C. under vacuum to yield 3.0 g (89percent) of the desired product.
89% With hydrogenchloride In ethanol; isopropyl alcohol at 5 - 20℃; for 2 h; A reaction vessel equipped with a magnetic stirrer was charged with pramipexole base (2.53 g) and absolute ethanol (20 ml).
The mixture was stirred at room temperature to afford a clear solution.
The solution was filtered and the filtrate was transferred to another reaction vessel.
A solution of about 14.6percent HCl in 2-propanol (7.8 ml) was added in portions and the resulting mixture was stirred for 1 hour.
The mixture was cooled to about 5° C. and stirred for additional 1 hour.
The precipitate was filtered, washed with cold ethanol and dried at 60° C. under vacuum to yield 3.0 g (89percent) of pramipexole dihydrochloride.
89.01% With hydrogenchloride In ethanol; water at 0 - 40℃; Example 4; Pramipexole dihydrochloride monohydrate(S)-(-)-2-Amino-6-(N-propylamino)-4,5,6,7-tetrahydrobenzothiazole (9.15 g, 43.28 mmol) in 500 ml round-bottom flask was dissolved in 30 ml of ethanol and water (0.78 g, 43.33 mmol) was added. A solution was cooled in an ice bath to 00C and gaseous HCl^)1 was blown through whereby a white precipitate fell out. The round- bottomed flask was sealed and it was stirred over night at room temperature. The next <n="16"/>day the precipitate was filtered off by suction and washed with a small amount of anhydrous ethanol. The precipitate was transferred into 100 ml round-bottom flask and anhydrous ethanol (50 ml) was added. The suspension was heated to 45°C and ethanol was evaporated on a rotatory evaporator. The process was repeated for another two times in order to drive out all of the excessive HCl(g). The product was recrystallized from methanol: a salt was dissolved in methanol (70 ml) at 450C, approximately 40 ml of methanol was evaporated and 20 ml of ethanol were added. It was cooled to room temperature and the resulting precipitate was filtered by suction, washed with some cooled anhydrous ethanol and dried in vacuum over P2O5 and NaOH. Yield: 11.631 g (89.01 percent) To the ethanolic solution of pramipexole water was added (27.6 ml, 1.53 mol) and solution was cooled to about -100C. Gaseous HCl(g) was introduced into the solution (200 g). The temperature of the solution and later the suspension must not exceed 250C during addition of gaseous HCl(g) . After the addition the suspension was heated to about 4O0C and concentrated to 2/3 of the volume. 2.65 1 of ethanol was added and the suspension was concentrated to 1/2 of the volume. Again 3.5 1 of ethanol was added and the suspension was concentrated to 1/2 of the volume. The solution was cooled to about -15°C and the product was separated by filtration. The product was dried at 25°C and finally at 400C on air.
88.7% With hydrogenchloride In ethanol; water at 0 - 5℃; for 7 - 8 h; lOOgm (0.4739mole) (S)-Pramipexole was dissolve in 800ml ethanol. Heat it to 50-55°C. Add lOgm-charcoal powder and stirr for 15-20 min. Filter through hyflow andwash it with 200ml ethanol. Add 8.53gm (0.4739mole) water cool the reaction mass to0-5°C. Pass dry HC1 gas to reaction mass till pH becomes 2. Stir for 7-8hrs. Filter theproduct. Purified by refluxing with ethanol.YIELD : 127gm(88.7percent)PURITY: 99.8percent
63.1% With hydrogenchloride In methanol Synthesis Example Example 12; Synthesis of (S)-2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole dihydrochloride. Pramipexole dihydrochloride; 4.40 g (7.36 mmol) of (S)-pramipexole (+)-di-p-toluyl-D-tartrate are dissolved in 88 mL of a 7.5percent Na2CO3 solution and 132 mL of dichloromethane; the phases are decanted and the lower organic phase is washed with 22 mL of deionized water. The phases are decanted and the resulting organic phase is dried with Na2SO4, filtered and concentrated under vacuum to a residue. The resulting residue is dissolved in 22 mL of methanol and bubbled on the HCl (gas) solution until the pH thereof is comprised between 2.5 and 3.8. It is vacuum-distilled to an internal volume of 12 mL and the suspension is stirred at 0°C. The crystals are filtered, washed with methanol and oven-dried to constant weight. 1.32 g (4.64 mmol, 63.1percent yield) of the title compound are obtained. αD= -66.5° (c = 1.0 methanol). Melting point: 274 - 284°C.
98.6 %Chromat. With hydrogenchloride In ethanol at 0℃; for 1.75 h; Compound (7a) free base [15.85 g, 0.075 mol, 98.7percent (AUC) asprepared above] in EtOH (105 mL) was cooled in an ice/water bath. Afterequilibrating for 30 min, HC1 in EtOH [prepared from adding AcCl (12 mL, 0.17mol) to EtOH (36 mL)] was added over 15 min. The mixture became a thickslurry that was difficult to stir. Additional EtOH (20 mL) was added. Afterstirring an additional 1 h in the ice/water bath, the solid was collected by filtrationand washed with cold EtOH (3 * 25 mL). The solid was dried on the filter funnelblowing N2 over the top. The solid was additionally dried in a vacuum oven at 40°C overnight to afford 20.71 g (97percent) of (7a)-2HCl at 98.6percent (AUC) by HPLCanalysis.[0081] The (7a)-2HCl from above was slurried in MeOH (60 mL). Themixture was difficult to stir. An additional 40 mL (in 2 x 20 mL increments) was added to allow stirring. The mixture was then heated to reflux. An additional 20 mL of MeOH was added to dissolve the solid (a total volume of 120 mL ofMeOH). Upon cooling to 45 °C (in 10 °C increments), the compound began tocrystallize. The mixture was cooled to ambient in 10 °C increments. Afterstirring overnight, the mixture was cooled in an ice/BbO bath. After equilibratingfor 1 h, the solid was collected by filtration washing with pre-chilled MeOH (3 x20 mL). The filtrate from the recrystallization was 98.6percent (AUC) by HPLCanalysis. The solid was dried in a vacuum oven overnight at 40 °C to afford 10.26g of a first crop of (7a)-2HCl (48percent) as white crystals: mp (DSC) 259.3-263.3 and265.8-283.5°C; [a]25D -62.5° (c 1.0, methanol); HPLC 99.1percent (AUC), fe = 2.8min; chiral HPLC >99percent (AUC), tR = 12.8 min. Anal. Calcd for CioHi9Cl2N3S: C,42.25; H, 6.74; Cl, 24.95; N, 14.78. Found: C, 42.28; H, 6.58; Cl, 24.83; N,14.63.

Reference: [1] Patent: EP1878731, 2008, A1, . Location in patent: Page/Page column 11
[2] Patent: CN107540633, 2018, A, . Location in patent: Paragraph 0088-0089; 0092-0093
[3] Patent: US2006/69263, 2006, A1, . Location in patent: Page/Page column 4
[4] Patent: US2006/148866, 2006, A1, . Location in patent: Page/Page column 5
[5] Patent: WO2008/97203, 2008, A1, . Location in patent: Page/Page column 14-15; 17
[6] Patent: WO2006/3677, 2006, A1, . Location in patent: Page/Page column 10; 19
[7] Patent: EP1884514, 2008, A1, . Location in patent: Page/Page column 10
[8] Patent: WO2006/12276, 2006, A1, . Location in patent: Page/Page column 21-22
[9] Patent: WO2008/41240, 2008, A1, . Location in patent: Page/Page column 18-19
[10] Patent: WO2008/41240, 2008, A1, . Location in patent: Page/Page column 19
[11] Patent: US2009/62549, 2009, A1, . Location in patent: Page/Page column 4
[12] Patent: WO2011/21214, 2011, A2, . Location in patent: Page/Page column 10; 15; 16
[13] Research on Chemical Intermediates, 2017, vol. 43, # 3, p. 1957 - 1968
  • 6
  • [ 943319-04-8 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
36% With hydrogenchloride; water In methanol at 3 - 8℃; for 2 h; To the reaction flask, the pure monohydrochloride salt of the compound of formula I (as obtained in the step C), methanol (600 ml) and cone, hydrochloric acid (33.67 ml) were charged and the reaction mass was stirred at a temperature of 3-8°C for 2 hours. To the reaction mass, activated charcoal (4g) was charged and the reaction mass was stirred for 30-45 minutes at temperature of 40-50°C. The activated charcoal was filtered through hyflo and filtrate was concentrated under vacuum to obtain residue. To the residue, isopropyl alcohol (700 ml) was charged and the reaction mass was maintained for 2-3 hours at 15-20°C to precipitate solid. The precipitated solid was then filtered and washed with isopropyl alcohol (100 ml). The solid was then dried under vacuum to yield dihydrochloride monohydrate salt of the compound of formula I. Yield 36percent, purity 99.77percent.
Reference: [1] Patent: WO2015/155704, 2015, A1, . Location in patent: Page/Page column 16-17
  • 7
  • [ 1001648-71-0 ]
  • [ 104632-25-9 ]
YieldReaction ConditionsOperation in experiment
87%
Stage #1: With hydrogenchloride; formic acid In water
Stage #2: With hydrogen In water
Example 9
(S)-Pramipexole dihydrochloride monohydrate (I*2 HCl*1 H2O)
To a solution of (6S,7S)-2-amino-7-hydroxy-6-(n-propyl)amino-4,5,6,7-tetrahydrobenzothiazole (the free base, compound of the formula VIII) (2.27 g) in formic acid (98-100percent, 31 g) was added concentrated hydrochloric acid (3.5 g).
The so obtained solution of (6S,7S)-2-amino-7-hydroxy-6-(n-propyl)amino-4,5,6,7-tetrahydrobenzothiazole-2 HCl was subjected to hydrogenation on palladium on carbon (10 wt.percent, 1.1 g) using the same reaction conditions as described in example 7.
The reaction mixture was diluted with methanol (30 ml), the catalyst was removed by filtration, washed with methanol, the combined filtrate and washings were concentrated to 10 g.
The syrupy residue was diluted with acetone (90 ml), the solution was cooled to 0-3°C, stirred at that temperature for 2 h and the precipitated crystals were collected by filtration.
The cake was washed with cold acetone and air-dried to give 2.63 g (87percent) product with m.p. 277-280°C.
Reference: [1] Patent: EP1878731, 2008, A1, . Location in patent: Page/Page column 11
  • 8
  • [ 123-38-6 ]
  • [ 106092-09-5 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: CN104496936, 2017, B, . Location in patent: Paragraph 0057; 0063; 0064; 0065; 0066
  • 9
  • [ 106092-09-5 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: WO2011/21214, 2011, A2,
[2] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
[3] Patent: WO2015/155704, 2015, A1,
[4] Patent: KR101546713, 2015, B1,
[5] Patent: CN104496936, 2017, B,
[6] Patent: CN107540633, 2018, A,
  • 10
  • [ 27514-08-5 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: WO2011/21214, 2011, A2,
[2] Patent: CN104496936, 2017, B,
  • 11
  • [ 106006-83-1 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: WO2011/21214, 2011, A2,
  • 12
  • [ 104617-50-7 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: WO2011/21214, 2011, A2,
  • 13
  • [ 873431-80-2 ]
  • [ 104632-25-9 ]
Reference: [1] Patent: WO2011/21214, 2011, A2,
  • 14
  • [ 113030-24-3 ]
  • [ 104632-25-9 ]
Reference: [1] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
  • 15
  • [ 4746-97-8 ]
  • [ 104632-25-9 ]
Reference: [1] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
  • 16
  • [ 144810-01-5 ]
  • [ 104632-25-9 ]
Reference: [1] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
  • 17
  • [ 159015-33-5 ]
  • [ 104632-25-9 ]
Reference: [1] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
  • 18
  • [ 404892-23-5 ]
  • [ 104632-25-9 ]
Reference: [1] Tetrahedron Asymmetry, 2014, vol. 25, # 16-17, p. 1239 - 1245
Same Skeleton Products
Historical Records