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[ CAS No. 7531-52-4 ] {[proInfo.proName]}

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Chemical Structure| 7531-52-4
Chemical Structure| 7531-52-4
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Product Details of [ 7531-52-4 ]

CAS No. :7531-52-4 MDL No. :MFCD00005253
Formula : C5H10N2O Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 114.15 Pubchem ID :-
Synonyms :

Calculated chemistry of [ 7531-52-4 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 33.66
TPSA : 55.12 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.61 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.73
Log Po/w (XLOGP3) : -0.87
Log Po/w (WLOGP) : -1.16
Log Po/w (MLOGP) : -0.78
Log Po/w (SILICOS-IT) : -0.02
Consensus Log Po/w : -0.42

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 0.07
Solubility : 133.0 mg/ml ; 1.17 mol/l
Class : Highly soluble
Log S (Ali) : 0.19
Solubility : 178.0 mg/ml ; 1.56 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.34
Solubility : 51.8 mg/ml ; 0.454 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.47

Safety of [ 7531-52-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 7531-52-4 ]

* 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 [ 7531-52-4 ]
  • Downstream synthetic route of [ 7531-52-4 ]

[ 7531-52-4 ] Synthesis Path-Upstream   1~15

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Reference: [1] Journal of Biological Chemistry, 1951, vol. 193, p. 81,87
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  • [ 24305-27-9 ]
Reference: [1] Pharmaceutical Chemistry Journal, 1988, vol. 22, # 2, p. 106 - 110[2] Khimiko-Farmatsevticheskii Zhurnal, 1988, vol. 22, # 2, p. 155 - 158
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  • [ 24305-27-9 ]
Reference: [1] Journal of Nanoscience and Nanotechnology, 2016, vol. 16, # 5, p. 5324 - 5332
  • 4
  • [ 7531-52-4 ]
  • [ 765-39-9 ]
Reference: [1] Patent: US2003/45536, 2003, A1,
[2] Patent: US2002/58667, 2002, A1,
  • 5
  • [ 7531-52-4 ]
  • [ 22795-99-9 ]
Reference: [1] Chemical Communications, 2013, vol. 49, # 77, p. 8686 - 8688
[2] Inorganic Chemistry, 2016, vol. 55, # 15, p. 7356 - 7372
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  • [ 35150-07-3 ]
Reference: [1] Tetrahedron Letters, 2011, vol. 52, # 42, p. 5435 - 5437
[2] Patent: WO2011/101861, 2011, A1, . Location in patent: Page/Page column 18
[3] Patent: WO2014/20462, 2014, A1, . Location in patent: Page/Page column 9
[4] Patent: CN107033054, 2017, A, . Location in patent: Paragraph 0070; 0071; 0073; 0074; 0111; 0113; 0114
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YieldReaction ConditionsOperation in experiment
96% With triethylamine In dichloromethane at 5℃; for 2 h; Inert atmosphere Example 1
To 2L reaction flask, 400mL dichloromethane and 38.4mL chloroacetyl chloride was added, under nitrogen protection, the substance inside the above mentioned reaction flask was cooled to 5°C; 50g L- prolinamide was dissolved in 600mL of dichloromethane to obtain a solution C, to solution C was added 67.5 mL of triethylamine to obtain solution D. At 5°C, the above solution D was slowly added dropwise into the reaction flask, allowing the substances in the reaction flask to react at 5°C for 2h.
(2) The first step's (1) substance in the reaction flask was concentrated under reduced pressure to remove dichloromethane, to the residue was then added 750mL water, 1500mL tetrahydrofuran and 500g of potassium carbonate, dissolved under stirring, after the substance in the reaction flask separates into layers, the aqueous layer was discarded. The remaining organic layer is concentrated under reduced pressure to give 80.2g of a slightly yellow solid substance. Thgrough identification, the slightly yellow solid material is the desired product (S)-1-(chloroacetyl)-pyrrolidine-2-carboxamide, the yield was 96percent , purity (HPLC) was 97.1percent
92% at 0℃; Reflux; Large scale L- prolinamide 9 (15kg, 131mol, 1.0eq.) In anhydrous tetrahydrofuran (100L), cooled to 0 , and thereto is added chloroacetyl chloride (18kg, 159mol, 1.2eq.). Upon complete addition stirring slowly raised to room temperature, then heated under reflux until reaction was completed. Distillation under reduced pressure to remove most of the low-boiling solvent, allowed to stand for cooling, the precipitated solid was lot was filtered, washed with tetrahydrofuran and dried in vacuo to give an off-white solid powder (23kg of, yield 92percent
90.7%
Stage #1: at 0℃; for 0.5 h;
Stage #2: With potassium carbonate In tetrahydrofuran at 0 - 20℃; for 4 h;
The compound S-prolinamide (11.2 g, 100mmol) add to a solution of chloroacetyl chloride (11.5 g, 100mmol) in tetrahydrofuran solution (200mL) which has been pre-cooled at 0 ° C, the solution is incubated at 0 ° C for 30 minutes, Potassium carbonate (27. 3g, 200mmol) is added to the mixed solution, the resulting mixed solution is incubated with stirring at 0 ° C for 1 hour, the reaction solution is then warmed at room temperature and stirring is continued for 3 hours.LC detection to the end of reaction, until the compound S-prolinamide disappeared completely after that, the reaction is filtered; the filter cake is washed with tetrahydrofuran (50mL), the combined filtrates. Rotate the solvent to get dryness, the residual oil is added to ethyl acetate to dissolve. The resulting ethyl acetate solution is washed with water (50mL × 2), dry over anhydrous sodium sulfate for 2 hours. After removing the desiccant, it is concentrated. After drying, obtained 17.2 g of compound (S)-1-(2-chloroacetyl) pyrrolidine-2-carboxamide (colorless oil), yield is 90.7percent.
89.5% at 60℃; 11.4 g (0.1 mol) of L-prolinamide was dissolved in 100 ml of tetrahydrofuran at 60 degrees, and 15 ml (0.2 mol) of chloroacetyl chloride was added. The temperature of the system was maintained at 60 degrees. The end point of the reaction was detected by HPLC and the reaction was completed after one hour. Heat filtration, washing the solids with tetrahydrofuran, drying and weighing to give a pale yellow solid 20.3g, yield 89.5percent, purity 98.2percent.
85% With potassium carbonate In acetonitrile at 10 - 20℃; for 1 h; In a clean round bottom flask, 100gm L-prolinamide, 1800m1 acetonitrile and 290.16gm K2C03were charged. The reaction mass was stirred, cooled to about 10-20°C and 108.8gm ofchioroacetyl chloride was added. Temperature of reaction mass was raised to about RT, stirred for about one hour, filtered, washed with acetonitrile and concentrated under vauum. 300m1 ethyl acetate was added to reaction mass, stirred at about 50-5 5 °C, cooled to about 0-5 °C and stirred for about 1-2 hour. The reaction mass was filtered, washed with ethyl acetate and driedunder vacuum and product isolated as a solid 13 0-140gm. (Yield: 77- 85percent; HPLC purity >97percent). Impurity H is less than 0.2percent w/w relative to the amount of compound of formula IV as determined by HPLC.
26 g With potassium carbonate In chloroform at 25 - 30℃; Example-2: Preparation of 1-chloroacetyl (S)-2-carboxamidepyrrolidine To a mechanically stirred solution of L-prolinamide (20 g), potassium carbonate (48.4 g) and chloroform (370 ml), the solution of chloroacetyl chloride (15.3 ml) in chloroform (30 ml) was added slowly over a period of 1 hour at temperature 25 to 30°C (exotherm observed till 40°C). Reaction mass was stirred for additional 2 hours at 25°C to 30°C. Upon completion of reaction, the reaction mass was filtered and the obtained solid was washed with chloroform (200 ml<2). Filtrate was dried over anhydrous sodium sulfate and filtrate was concentrated under reduced pressure to get residue. Ethyl acetate (100 ml) was added to the residue at temperature 25°C to 30°C and the slurry was stirred for 30 minutes. Obtained solid was filtered and washed with ethyl acetate (20 ml) and dried under vacuum at 35°C to 40°C for 5 to 6 hours. [Yield: 24 to 26 g]

Reference: [1] Patent: CN103896819, 2016, B, . Location in patent: Paragraph 0017; 0018; 0019
[2] Patent: CN105503878, 2016, A, . Location in patent: Paragraph 0017
[3] Patent: CN105884669, 2016, A, . Location in patent: Paragraph 0059-0063
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 13, p. 2774 - 2789
[5] Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2362 - 2365
[6] Patent: CN107793341, 2018, A, . Location in patent: Paragraph 0049-0064
[7] Patent: WO2014/102815, 2014, A1, . Location in patent: Page/Page column 15
[8] Tetrahedron Letters, 1998, vol. 39, # 39, p. 6991 - 6992
[9] Patent: WO2004/92127, 2004, A1, . Location in patent: Page 10
[10] Patent: US2010/256080, 2010, A1, . Location in patent: Page/Page column 6
[11] Patent: US2006/217428, 2006, A1, . Location in patent: Page/Page column 8; 9
[12] Patent: WO2011/12322, 2011, A2, . Location in patent: Page/Page column 41
[13] Patent: WO2011/101861, 2011, A1, . Location in patent: Page/Page column 20
[14] Letters in Organic Chemistry, 2013, vol. 10, # 3, p. 159 - 163
[15] Patent: WO2013/179300, 2013, A2, . Location in patent: Page/Page column 27
[16] Patent: EP2865666, 2015, A1, . Location in patent: Paragraph 0157; 0165
[17] Organic Process Research and Development, 2015, vol. 19, # 4, p. 551 - 554
[18] Patent: WO2015/92806, 2015, A1, . Location in patent: Sheet 11
[19] Patent: WO2015/145467, 2015, A1, . Location in patent: Page/Page column 21-22
[20] Patent: CN106699627, 2017, A, . Location in patent: Paragraph 0041-0043
[21] Patent: CN107311908, 2017, A, . Location in patent: Paragraph 0037; 0041; 0045; 0047; 0048; 0049
[22] Patent: CN104945299, 2017, B, . Location in patent: Paragraph 0038; 0039; 0040; 0044; 0045; 0046; 0050-0052
[23] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 15, p. 4402 - 4409
[24] Patent: CN104262227, 2018, B, . Location in patent: Paragraph 0015-0030
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Reference: [1] Letters in Organic Chemistry, 2013, vol. 10, # 3, p. 159 - 163
[2] Patent: WO2014/20462, 2014, A1,
[3] Patent: CN107033054, 2017, A,
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YieldReaction ConditionsOperation in experiment
92%
Stage #1: With potassium carbonate In acetonitrile at 0 - 15℃;
Stage #2: at 0 - 15℃;
A process for the preparation of (S) -l_ (2-chloroacetylchloride) -2-cyanopyrrolidine, comprising the steps of: dissolving L-prolinamide (2 (0.17511101) Potassium carbonate (488,0.348111 0 1)To 4001 ^ acetonitrile, 0-15 ° (: stirring slowly dropping 16mL (0.2lmo 1)Chloroacetyl chloride (drop time 2-3 hours), after the completion of dropping, stirring room temperature overnight, TLC plate anti-Should be completely, the suction filter, the filtrate 0_15 ° C stirring drop 13.4111 to 0.094111 011 44, after the completion of the drop, 25 ° (: under stirringAfter overnight, the TLC plates were allowed to react completely, spin-dried, and then 20 mL of ethyl acetate was added to the kettle to carry excess TFAA,The residue was dissolved in 150 mL of ethyl acetate, the pH was adjusted to 8 with sodium carbonate solution, and the organic phase was washed with saturated brine,Dried over anhydrous sodium sulfate, filtered and dried to give an oil which was allowed to stand overnight and solidify (if not solidified,Seed crystal) as a light brown solid (Compound 2) in a yield of 92percent.
92%
Stage #1: With potassium carbonate In acetonitrile at 0 - 20℃;
Stage #2: at 0 - 25℃;
L-prolinamide (20 g, 0.175 mol),Potassium carbonate (48 g, 0.34 mol) was added to 400 mL of acetonitrile,(0.21 mol) of chloroacetyl chloride (dropwise for 2-3 hours) was slowly added dropwise with stirring at 0 to 15 ° C,After completion of the dropwise addition,The reaction was stirred at room temperature overnight,After TLC plate reaction was complete,Filtration,The filtrate was stirred at 0-15 ° C and 13.4 mL (0.094 m) of TFAA was added dropwise,After completion of the dropwise addition,Stir overnight at 25 ° C,After TLC plate reaction was complete,Drying,Then, 20 mL of ethyl acetate was added to the autoclave to carry out excess TFAA,So repeated 3 times,The residue was dissolved in 150 mL of ethyl acetate,The pH was adjusted to 8 with sodium carbonate solution, and the organic phase was washed with saturated brine,Dried over anhydrous sodium sulfate,filter,Drying,To give an oil,Standing overnight,Curing (such as curing,Can be added before standing a little seed)12.2 g of a light brown solid (compound 2)Yield 92percent.
83.4%
Stage #1: With trifluoroacetyl chloride In N,N-dimethyl-formamide at 50℃; for 1.5 h;
Stage #2: With trifluoroacetyl chloride In N,N-dimethyl-formamide at 60℃; for 1.5 h;
The reaction bottle into the 92.0 g trichlor and 6.4 g DMF, under stirring added in batches 8.0 g (S)- N - chloracetyl -2 - carbamino pyrrolidine, 60 °C reaction 1.5 h. After the reaction is distilled under reduced pressure steam out of the oxysilane.After treatment in the light of the embodiment 1, in the crystallization from toluene, shall be 6.0 g, yield 83.4percent.
66%
Stage #1: at 15 - 35℃; for 2 h;
Stage #2: With 1,3,5-trichloro-2,4,6-triazine In Isopropyl acetate; N,N-dimethyl-formamide at 25 - 35℃; for 0.75 h;
EXAMPLE 3; This example illustrates the synthesis of a compound of formula (IV) in accordance with the invention.Synthesis of 1-chloroacetyl-2-cyanopyrrolidine. A 250 mL reactor with thermometer, condenser and magnetic stirring was charged with i-PrOAc (41 mL), dry DMF (5 mL) and chloroacetyl chloride (19.5 g, 173 mmol) under an inert atmosphere. The resulting solution was cooled to 15° C. and a solution of L-prolinamide (17.1 g, 150 mmol) in dry DMF (48 mL) was slowly added (IT35° C.). The reaction mixture was stirred 2 additional hours at 35° C. to obtain complete conversion. The internal temperature was adjusted to 25° C. and cyanuric chloride (13.8 g, 75 mmol) was added in portions (IT35° C.). The mixture was stirred for 45 minutes, poured into 200 mL of water and extracted with EtOAc (3.x.200 mL). The organic phase was washed with 5percent aqueous NaHCO3 (2.x.200 mL), dried over Na2SO4, filtered, and the solvents were evaporated under vacuum. The resulting oil was crystallized in 65 mL of isopropanol to obtain 17.16 g of 1-chloroacetyl-2-cyanopyrrolidine (66percent yield).
5.2 g
Stage #1: at 25 - 30℃;
Stage #2: With 2,6-dimethylpyridine In dichloromethane for 0.25 h;
Stage #3: With trichlorophosphate In dichloromethane at 5 - 20℃;
Exampie-8: Preparation of 1-chloroacetyl (S)-2-cyanopyrroiidine To a mechanically stirred solution of L-prolinamide (5g), and dichloromethane (40 ml), solution of chloroacetyl chloride (3.76 ml) in dichloromethane (10 ml) was added drop-wise over a period of 20-25 minute at temperature 25 to 30°C, exotherm observed till 40°C. Reaction mass was then stirred for additional 3 h at 25 to 30°C. 2, 6 lutidine (14.1 ml) was added to reaction mass and stirred for 15 minutes. Solution of POCI3 (6.12 ml) in dichloromethane (10 ml) was added slowly to reaction mass at 5 to 10°C. The reaction mass was stirred for 2-3 h at room temperature. Upon completion of reaction, the reaction mass was cooled to 0-5°C. DM water was slowly added to reaction mass, exotherm observed upto 40°C. Organic layer was washed with NaHCO3 solution (2X50 ml), followed by washing with aqueous 6percent HCI (3 X 30 ml) and DM water (2X30 ml). Organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure to give 1-chloroacetyl (S)-2-cyanopyrrolidine. [Yield: 5.2 gm; Purity: 97.31percent]

Reference: [1] Patent: CN106045891, 2016, A, . Location in patent: Paragraph 0046; 0047-0049
[2] Patent: CN105523985, 2016, A, . Location in patent: Paragraph 0054; 0055
[3] Patent: CN107501154, 2017, A, . Location in patent: Paragraph 0068-0108
[4] Patent: US2008/167479, 2008, A1, . Location in patent: Page/Page column 5
[5] Patent: US6432969, 2002, B1,
[6] Patent: WO2013/179300, 2013, A2, . Location in patent: Page/Page column 30
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  • [ 7531-52-4 ]
  • [ 207557-35-5 ]
Reference: [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 13, p. 2774 - 2789
[2] Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2362 - 2365
[3] Patent: WO2011/101861, 2011, A1,
[4] Letters in Organic Chemistry, 2013, vol. 10, # 3, p. 159 - 163
[5] Patent: WO2014/20462, 2014, A1,
[6] Patent: WO2014/102815, 2014, A1,
[7] Patent: EP2865666, 2015, A1,
[8] Organic Process Research and Development, 2015, vol. 19, # 4, p. 551 - 554
[9] Patent: WO2015/145467, 2015, A1,
[10] Patent: CN105884669, 2016, A,
[11] Patent: CN104945299, 2017, B,
[12] Patent: CN106966947, 2017, A,
[13] Patent: CN106966947, 2017, A,
[14] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 15, p. 4402 - 4409
[15] Patent: CN108689905, 2018, A,
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  • [ 1166227-08-2 ]
Reference: [1] Patent: WO2009/80705, 2009, A2, . Location in patent: Page/Page column 52
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  • [ 1166227-08-2 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3569 - 3574
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  • [ 141774-70-1 ]
Reference: [1] Patent: US2018/72743, 2018, A1,
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  • [ 7531-52-4 ]
  • [ 1217486-61-7 ]
Reference: [1] Patent: WO2012/117071, 2012, A1, . Location in patent: Page/Page column 23
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  • [ 1217486-61-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 13, p. 3741 - 3748
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