Name: 4524-93-0|Cyclopentanecarbonyl chloride|98%
Brand: Ambeed
SKU: A101710
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2
[ 3400-45-1 ]
[ 4524-93-0 ]

Yield	Reaction Conditions	Operation in experiment
97.4%	With thionyl chloride at 40 - 50℃; for 2h;	1; 4 Example 1-Preparation of Cyclopentanoyl Chloride 262.7g of thionyl chloride was added into the reaction flask, stirred, heated to 40-50°C, and 210g of cyclopentanoic acid was added dropwise. After the addition was completed, the reaction was kept at 40-50°C for 2 hours. The post-treatment was concentrated under reduced pressure to remove excess thionyl chloride to obtain 237.5 g of cyclopentanoyl chloride with a yield of 97.4%.
88.5%	With thionyl chloride for 3h; Heating;
86%	With thionyl chloride In dichloromethane at 0℃; for 15h; Inert atmosphere;	49.1 Step 1: Cyclopentanecarbonyl chloride [00561] To a stirred solution of cyclopentanecarboxylic acid (10.0 g, 87.6 mrnoi) in DCM (100 mL) was added SOCb (14.8 mL, 175.22 mmol). The mixture was stirred at 0 °C for 15 hours under nitrogen atmosphere. The reaction was concentrated to afford the title compound (10 g, 86%) as a yellow oil wdiich was used without further purification.

83.5%	With thionyl chloride for 2h; Ambient temperature;
75%	With thionyl chloride
	With phosphorus trichloride
	With thionyl chloride
	With thionyl chloride
	With thionyl chloride for 1h; Heating;
	With thionyl chloride at 60℃; for 2h;
	With pyridine; thionyl chloride In benzene at 50℃; for 2h;
	With sulfuryl dichloride
	With thionyl chloride In toluene at 70℃; for 2h;
	With pyridine; thionyl chloride Heating;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide
	With oxalyl dichloride at 20℃; for 0.5h;	4 Preparation 4: 1- (CYCLOPenTylcarbonyl) piperazine. Preparation 4: 1- (CYCLOPenTylcarbonyl) piperazine. Cyclopentane carboxylic acid (5.0 g, 44 MMOL) was dissolved in chloroform (50 ML). Oxalyl chloride (4.6 ML, 52.5 MMOL) was added dropwise under nitrogen and stirred at room temperature for 30 min. The reaction mixture was then heated under reflux for 1 h, before concentrating in vacuo to give cyclopentanecarbonyl chloride as a light yellow liquid. Piperazine hexahydrate (8.55 g, 44.0 MMOL) was dissolved in absolute ethanol (50 ml) and then refluxed for 10 min. Cyclopentanecarbonyl chloride (5.83 g, 44 MMOL) was added dropwise at 65No.x0;C and the reaction mixture was refluxed for 30 min and then stirred at room temperature for 18 h. The reaction mixture was cooled, filtered and the filtrate was concentrated in vacuo to GIVE-20 MI of solution. The concentrate was cooled and then filtered again. Ethanolic hydrogen chloride was added to the mother liquor and the reaction mixture was concentrated to give a white solid, which was dissolved in water (15 ML). The solution was basified to pH 14 and the product was extracted with dichloromethane (7 x 50 ML). The extracts were dried (NA2SO4) and concentrated to give the title compound as a yellowish residue, which was distilled to give the product (1.28 g, 7.0 mmol, 16%) Preparation 10: 4- (8-azabicyclo[3.2.1]oct-3-ylsulfanyl) phenyl methyl ether To a stirred solution of 2,2,2-trichloroethyl 3- [ (4-methoxyphenyl) sulfanyl]-8- azabicyclo[3.2.1]octaNE-8-carboxylate (Preparation 11,52. 7 g, 0.12 moles) in tetrahydrofuran under nitrogen was added zinc dust (20 g, ) and potassium hydrogenphosphate (1 M, 125 ML). The reaction mixture was stirred for 2 h at room temperature before adding more zinc dust (30 g) followed by heating on a steam bath for 30 min. The reaction mixture was cooled to room temperature and diluted with water (11). Sodium carbonate was added to adjust the pH to 10. The reaction mixture was filtered and the filtrate was separated and then extracted with dichloromethane. The combined organic extracts were dried (NA2S04) and concentrated in vacuo to give the title compound as a yellow oil (26.0 g, 84%). The oil was purified by column chromatography on silica gel (350 g) ELUTING with methanol : dichloromethane : 0.88 ammonia solution (10: 90: 1) to give the product as an oil which crystallised on standing (13 g, 42%). The solid was further purified by stirring in ether and filtering to give a light yellow solid (9 g, 29%).
	With hydrogenchloride; thionyl chloride; tin(IV) chloride In thiophene; dichloromethane	33.a 33a. 33a. 2-Thienyl cyclopentyl ketone Cyclopentanecarboxylic acid chloride, prepared from 100 mmol cyclopentanecarboxylic acid and 120 mmol of thionyl chloride, was dissolved in 100 mL of methylene chloride, and the solution was cooled in an ice bath. Thiophene (13.4 mL, 100 mmol) and SnCl4 (25 mL of a 1M solution in methylene chloride) were added. The reaction was warmed to room temperature and stirred for 72 hours. The reaction was quenched with 1 N HCl, and the mixture was extracted with three portions of methylene chloride.
	With 4-methyl-morpholine; isobutyl chloroformate at -10℃; for 0.5h;	16.1 To a solution of cycopentylcarboxylic acid (15 mL, 138. 4 mmol) and NMM (30. 4 mL. 276.8 mmol) cooled at-10 °C were added isobutyl chloroformate (18 mL,-138. 4 mmol). The reaction mixture was stirred at-10 °C for 30 min and N, O- dimethylhydroxylamine hydrochloride (13.8 g, 138. 4 mmol) was added. The reaction was stirred and warmed to room temperature for 3 h, and then poured into water (200mL), extracted with EtOAc (2 x 200 mL), dried over Mg S04 and concentrated. The residue was purified by flash column chromatography (30% EtOAc in hexane) to afford 19.11 g of product (88%) as colorless oil. 1H NMR (CDC13) : 6 1.56-1. 68 (m, 3H), 1.71-1. 90 (m, 5H), 3. 12 (m, 1H), 3.22 (s, 3H), 3.73 (s, 3H). IR (cm-l) 1637.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 4h;	14.A Example 14; 2-{2-[4-(2,5-Dichlorophenyl)-1-piperazinyl]-ethyl}-2-azaspiro[4.4]nonane-1,3-dione; Ethyl cyclopentanecarboxylate (14A) 0.15 g (1.2 mmol) of oxalyl chloride was added dropwise at 0°C to a stirred solution of 0.11 g (1 mmol) of cyclopentanecarboxylic acid in 10 ml of CH2Cl2 and 2 drops of DMF. The solution was then stirred at room temperature for 4 hours. The solvent was evaporated off, the residue dissolved in 10 ml of CH2Cl2 and this solution was added dropwise at 0°C to 10 ml of ethanol. After 20 hours' stirring at room temperature, the solvents were evaporated to dryness and the residue purified by flash chromatography eluding with petroleum ether:ethyl acetate 98:2 to give 0.042 g (32%) of the desired compound. 1H-NMR (CDCl3, δ): 1.27 (t, 3H, CH2CH 3), 1.44-1.98 (m, 8H, cyclopentane CH2s), 2.61-2.82 (m, 1H, CH), 4.11 (q, 2H, CH 2CH3).
	With oxalyl dichloride In dichloromethane at 0 - 20℃;	To a solution of cyclopentanecarboxylic acid (10.0 g, 87.6 mmol) and DMF (0.1 mL) in CH2CI2 (100 mL) was added oxalyl chloride (16.68 g, 131.42 mmol) dropwise slowly at 0 0C. The reaction mixture was then stirred at ambient temperature for 2 hours and distilled in vacuo to afford cyclopentanecarbonyl chloride (6.71 g) as a pale yellow liquid.
	With phosphorus pentachloride In diethyl ether Inert atmosphere; Cooling;
	With thionyl chloride for 2h; Reflux;	7 Reference Example 7; 2-cyclopentanecarbonyl malonic acid diethyl ester; Cyclopentanecarboxylic acid (10 g, 88 mmol) was heated under reflux with thionyl chloride (13 mL, 176 mmol). After 2 hrs, excess thionyl chloride was distilled under reduced pressure and the acid chloride (9.8 g) was collected as a liquid.In another vessel, sodium hydride (50% dispersion in oil, 4.28 g, 89 mmol) was suspended in THF (100 mL) and diethyl malonate (11.9 g, 74.2 mmol) was added dropwise at 0° C. The previously-prepared acid chloride (9.8 g, 74 mmol) was added dropwise at 0° C. and the mixture stirred at room temperature for 1 hr. The mixture was quenched with cold water and extracted with ethyl acetate. The organic layer was washed with water, sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated to afford 2-cyclopentanecarbonyl malonic acid diethyl ester (19.2 g, 85%) as a liquid.
	With thionyl chloride at 100℃; for 1h;	5.1.8. 1-Cyclopentanecarbonyl-1H-indazole-3-carboxylic acid ethyl ester, 6d Cyclopentanecarboxylic acid (0.525 mmol) dissolved in SOCl2 (1 mL) was stirred at 100 °C for 1 h. After cooling, the excess SOCl2 was removed in vacuo, and the residue was dissolved in cold anhydrous toluene (3-4 mL). To this solution, a mixture of 1H-indazole-3-carboxylic acid ethyl ester 432 (0.525 mmol) and Et3N (0.577 mmol) in toluene anhydrous (3 mL) was added, and the suspension was stirred at 110 °C for 5 h. After cooling, the precipitate was filtered off, the solvent was evaporated in vacuo, cold water (15 mL) was added, and resulting mixture was neutralized with 0.5 N NaOH and extracted with CH2Cl2 (3 × 15 mL). Evaporation of the solvent resulted in the final compound 6d. Yield = 86%; oil; 1H NMR (CDCl3) δ 1.55 (t, 3H, OCH2CH3, J = 7.2 Hz), 1.75-1.85 (m, 4H, cC5H9), 1.95-2.05 (m, 2H, cC5H9), 2.10-2.20 (m, 2H, cC5H9), 4.20-4.30 (m, 1H, cC5H9), 4.60 (q, 2H, OCH2CH3, J = 7.2 Hz), 7.50 (t, 1H, Ar, J = 8.0 Hz), 7.60 (t, 1H, Ar, J = 8.4 Hz), 8.25 (d, 1H, Ar, J = 8.0 Hz), 8.50 (d, 1H, Ar, J = 8.4 Hz). Anal. (C16H18N2O3) C, H, N.
	With oxalyl dichloride In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride for 3h; Reflux; Inert atmosphere;
	With thionyl chloride for 2h; Reflux;
16 g	With thionyl chloride In toluene for 3h; Reflux;	1.1 To a solution of A (15 g, 0.13 mol) in toluene (50 mL) was added SOCI2 (15 mL). The reaction mixture was refluxed for 3h. Toluene was removed under reduced pressure. The acid chloride product was obtained as a brown liquid (16 g) and used in the next step directly.
	With thionyl chloride at 90℃; for 2h;
	With thionyl chloride at 80 - 90℃; for 1h;
	With thionyl chloride for 3h; Reflux;
	With oxalyl dichloride
	With oxalyl dichloride
	With thionyl chloride In dichloromethane Reflux;
	With oxalyl dichloride In dichloromethane at 20℃; for 3h; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	Compounds 11 and 12. General procedure for the cyclic aliphatic esterification of 7 General procedure: 2.5 eq. of the appropriate carboxylic acid (cyclopentanecarboxylic acid, cyclohexanecarboxylic acid respectively) were dissolved in dry DCM and cooled down to 0 °C in an ice bath. 3 eq. oxalyl chloride were added dropwise. Then 2 drops of DMF are added at rt and the reaction is stirred for 1 h at rt. After the gas development is complete, the mixture is cooled to 0 °C again. 2.5 eq. TEA are added slowly under the liquid surface. Finally, a mixture of 1 eq. 7 and 1.2 eq. TEA was added to the reaction and stirred for 24 h at rt. The solvent was evaporated and the residue was purified with a column chromatography on silica gel using CHCl3/Acetone/MeOH (75:20:5) to give the ester derivatives (Rf(11)=0.45, Rf(12)=0.50) in 71% (11) and 77% (12) yield as pale yellow resin-like solid.
	With thionyl chloride; N,N-dimethyl-formamide In toluene at 70℃; for 3h;
	With thionyl chloride for 2h; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.5h;	3 Example 3 Dichloromethane containing cyclohexylcarboxylic acid (21.2 g, 186 mmol) is added at room temperatureIn a flask with (200 ml) solution, oxalyl chloride (20.2 mL, 241.4 mmol) and DMF (0.5 mL, 6.5 mmol) were added dropwise, wherein the molar concentration of the carboxylic acid used was 0.9 mol/L.The resulting mixture was stirred at room temperature for 0.5 h and then concentrated under vacuum.Dichloromethane and excess oxalyl chloride were removed and the resulting oil was acid chloride (20 mL, ca. 186 mmol) ready for use.
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 24℃; Inert atmosphere;
	With thionyl chloride for 2h; Heating / reflux;	252 Reference Example 252: 2-Cyclopentanecarbonyl malonic acid diethyl ester. Cyclopentanecarboxylic acid (10.0 g, 87.7 mmol) was heated under reflux with thionyl chloride (13 mL, 176 mmol). After 2 hrs the thionyl chloride was distilled under reduced pressure to give the crude acid chloride (9.8 g, 74.2 mmol) as a liquid. In another vessel, 50 % sodium hydride (4.28 g, 89.09 mmol) was taken up in THF (100 mL) and diethyl malonate (11.88 g, 74.24 mmol) was added dropwise at 0°C. Mo this mixture the previously-prepared acid chloride (9.8g, 74.2 mmol) was added dropwise at 00C and the reaction mixture was stirred at r.t. for an hour. The reaction was quenched with cold water and extracted with ethyl acetate. The combined organic layer was washed with water, sodium bicarbonate solution, brine solution, dried over sodium sulfate, filtered and concentrated to afford_2-cyclopentanecarbonyl malonic acid diethyl ester (19.2 g, 85.5 %) as a liquid.
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide for 2h;
	With thionyl chloride In dichloromethane for 6h; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 6h;
	With oxalyl dichloride In N,N-dimethyl-formamide
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 40℃; for 10h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 35℃; for 1.5h; Inert atmosphere;
	With thionyl chloride; N,N-dimethyl-formamide at 50℃; for 3h; Inert atmosphere;	a 2-Chloro-l-cvclopentylethan-l-one, Intermediate DM Step a: To a mixture of cyclopentanecarboxylic acid (3.00 g, 26.2 mmol) in SOCl2 (10.0 mL) was added DMF (2 drops), and the resulting mixture was stirred at 50 °C for 3 hours under N2 atmosphere. The mixture was concentrated in vacuo to give a residue, which was dissolved in DCM (30.0 mL) and then re-concentrated in vacuo to give cyclopentanecarbonyl chloride (3.40 g, 98% crude yield) as a colorless oil.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25℃; for 3h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; Schlenk technique;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃;
	With thionyl chloride for 2h; Reflux;	General procedure: To a suspension of corresponding acid (2.5 mmol, 2.5 eq) in dichlorosulfoxide (6 mL) was heated to reflux for 2h. The mixture was concentrated under reduced pressure and dissolved with suitable dichloromethane without further purification.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Cooling with ice;	33 Example 33. Preparation of compound 33 with lappaconitine and cyclopentanoic acid: Weigh 116mg of cyclopentanoic acid into a 25ml dry round bottom flask, add 5ml of dry dichloromethane to dissolve it, add a few drops of dimethylformamide, and add 375mg of oxalyl chloride in an ice bath. After reacting at room temperature for 2 hours, cyclopentanoyl chloride is prepared. Weigh 107 mg of N-deacetyllappaconitine in a 25 ml round-bottom flask, and add 10 ml of dry dichloromethane to dissolve it. Add 105μl of dry pyridine under the protection of Ar gas, slowly add the prepared acid chloride dropwise to the substrate solution, and react at 35°C. The progress of the reaction is checked by thin-layer chromatography. The reaction is complete after 15 hours. Add dropwise saturated sodium carbonate aqueous solution to the reaction solution, adjust the pH value of the reaction solution to 10, extract the reaction solution with dichloromethane, and dry the dichloromethane layer with anhydrous sodium sulfate. The solid sodium sulfate was filtered off, and the dichloromethane was spin-dried to obtain the crude product, which was separated and purified by column chromatography to obtain the target compound. Its structure and characteristics are as follows:
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃;	Acyl chlorides General procedure: The acid (5 mmol) was dissolved in anhydrous CH2Cl2 (10 mL) and DMF (a few drops) added.Oxalyl chloride (6 mmol, 1.2 equiv.) was added dropwise to the solution, that was cooled in an icewater bath. The resulting mixture was allowed to stir at room temperature for an additional 4 h andthe solvent was evaporated to afford the crude acyl chloride, which was used directly in the nextstep.
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;

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[50]Lee, Minhan; Jung, Hoimin; Kim, Dongwook; Park, Jung-Woo; Chang, Sukbok [Journal of the American Chemical Society, 2020, vol. 142, # 28, p. 11999 - 12004]
[51]Wang, Xing-Rong; Wang, Shuai; Li, Wen-Bo; Xu, Kai-Yan; Qiao, Xue-Peng; Jing, Xue-Li; Wang, Zi-Xiao; Yang, Chang-jiang; Chen, Shi-Wu [European Journal of Medicinal Chemistry, 2021, vol. 213]
[52]Current Patent Assignee: SOUTHWEST JIAOTONG UNIVERSITY - CN113105391, 2021, A Location in patent: Paragraph 0275-0279
[53]Flavell, Robert R.; Liu, Jianbo; Parker, Matthew F. L.; Toste, F. Dean; Wang, Sinan; Wilson, David M. [Chem, 2021, vol. 7, # 8, p. 2245 - 2255]
[54]Zhang, Peng; Zeng, Jia; Pan, Ping; Zhang, Xue-Jing; Yan, Ming [Organic Letters, 2022, vol. 24, # 2, p. 536 - 541]

3
[ 4524-93-0 ]
[ 825-41-2 ]
[ 5540-57-8 ]

Reference： [1]Journal of Medicinal Chemistry,1966,vol. 9,p. 428 - 430

4
[ 4524-93-0 ]
[ 693-05-0 ]
[ 72104-46-2 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 19 - 25

5
[ 4524-93-0 ]
[ 20207-16-3 ]
2-(Cyclopentanecarbonyl-amino)-3-oxo-butyric acid ethyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1986,vol. 34,p. 2840 - 2851

6
[ 4524-93-0 ]
[ 33544-42-2 ]
Cyclopentanecarboxylic acid N'-(3-nitro-pyridin-4-yl)-hydrazide; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2474 - 2485

7
[ 4524-93-0 ]
[ 139525-77-2 ]
S 20934 [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 3231 - 3239

8
[ 4524-93-0 ]
[ 772-54-3 ]
2-(Cyclopentylmethanoyl)-1-<(diethylamino)methyl>benzene [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1995,vol. 60,p. 2298 - 2301

9
[ 4524-93-0 ]
[ 20896-27-9 ]
5-Chloro-4-(cyclopentanecarbonyl-amino)-2-methoxy-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane for 4h; Ambient temperature;

Reference： [1]Ohmori; Maeno; Hidaka; Nakato; Matsumoto; Tada; Hattori; Sakamoto; Tsukamoto; Usuda; Mase [Journal of medicinal chemistry, 1996, vol. 39, # 14, p. 2764 - 2772]

10
[ 4524-93-0 ]
[ 13020-57-0 ]
Cyclopentanecarboxylic acid 3-benzoyl-phenyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,1996,vol. 4,p. 2115 - 2134

11
[ 4524-93-0 ]
[ 161356-05-4 ]
Cyclopentanecarboxylic acid 4-phenylsulfamoyl-phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 25℃;

Reference： [1]Imaki, Katsuhiro; Okada, Takanori; Nakayama, Yoshisuke; Nagao, Yuuki; Kobayashi, Kaoru; Sakai, Yasuhiro; Mohri, Tetsuya; Amino, Takaaki; Nakai, Hisao; Kawamura, Masanori [Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 12, p. 2115 - 2134]

12
[ 4524-93-0 ]
[ 24358-43-8 ]
cyclopentanecarboxylic acid [1-(3-chloro-phenyl)-ethyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 20℃; for 2h;

Reference： [1]Ho, Bin; Michael Crider; Stables, James P [European Journal of Medicinal Chemistry, 2001, vol. 36, # 3, p. 265 - 286]

13
[ 4524-93-0 ]
[ 405224-24-0 ]
cyclopentanecarboxylic acid (5-bromo-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridin-3-yl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1577 - 1580

14
[ 4524-93-0 ]
[ 631-36-7 ]
[ 6635-67-2 ]

Yield	Reaction Conditions	Operation in experiment
	With aluminium trichloride In dichloromethane for 18h; Heating;

Reference： [1]Qin, Jun; Friestad, Gregory K. [Tetrahedron, 2003, vol. 59, # 34, p. 6393 - 6402]

15
[ 4524-93-0 ]
phenylmagnesium bromide [ No CAS ]
[ 5422-88-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	With vanadium(III) chloride In diethyl ether; dichloromethane at -78 - 20℃;

Reference： [1]Qin, Jun; Friestad, Gregory K. [Tetrahedron, 2003, vol. 59, # 34, p. 6393 - 6402]

16
[ 4524-93-0 ]
[ 3196-23-4 ]
[ 60433-01-4 ]

Reference： [1]Russian Journal of General Chemistry,2004,vol. 74,p. 933 - 936

17
[ 4524-93-0 ]
[ 40230-24-8 ]
cyclopentanecarboxylic acid-(4,6-diphenyl-pyrimidin-2-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 6529 - 6540

18
[ 4524-93-0 ]
[ 129-44-2 ]
C₂₆H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With pyridine In N,N-dimethyl-formamide at 20℃; for 24h;

Reference： [1]Huang, Hsu-Shan; Chiu, Hui-Fen; Tao, Chi-Wei; Chen, In-Been [Chemical and Pharmaceutical Bulletin, 2006, vol. 54, # 4, p. 458 - 464]

19
[ 4524-93-0 ]
[ 17361-44-3 ]
C₃₄H₆₇NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Cyclopentanecarboxylic acid chloride With pyridine In 1-methyl-pyrrolidin-2-one at 20℃; Stage #2: ditetradecylamine In tetrahydrofuran at 20℃; Further stages.;

Reference： [1]Chang, Young-Tae; Choi, Jaehwa; Ding, Sheng; Prieschl, Eva E.; Baumruker, Thomas; Lee, Jae-Mok; Chung, Sung-Kee; Schultz, Peter G. [Journal of the American Chemical Society, 2002, vol. 124, # 9, p. 1856 - 1857]

20
[ 4524-93-0 ]
[ 137215-27-1 ]
CH₃OCCHCOC₆H₃SCOCHC₄H₈ [ No CAS ]

Reference： [1]Phytochemistry,2007,vol. 68,p. 811 - 818

21
[ 4524-93-0 ]
[ 24922-00-7 ]

Yield	Reaction Conditions	Operation in experiment
89%		6a) Ethyl 3-cyclopentyl-3-oxopropanoate To a solution of monoethyl malonate (13.6 mL, 115 mmol) and a few milligrams of 2,2'-bipyridyl at between -55 and -65 C. was slowly added a 2.4 M solution of n-butyl lithium in hexanes (92.0 mL, 230 mmol). After the addition was complete, cyclopentanecarbonyl chloride (7.0 mL, 58 mmol) was added in portions. The solution was then allowed to stir while warming to ambient temperature and was poured into a mix of 1 N aqueous hydrochloric acid and ether. The layers were separated and the ether layer was washed three times with saturated sodium bicarbonate, dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution) to afford ethyl 3-cyclopentyl-3-oxopropanoate (9.50 g, 89%). 1H-NMR (400 MHz, DMSO-d6) delta 4.06 (q, J=7 Hz, 2H), 3.60 (s, 2H), 2.99-2.91 (m, 1H), 1.78-1.47 (m, 8H), 1.15 (t, J=7 Hz, 3H).

Reference： [1]Patent: US2008/96921,2008,A1 .Location in patent: Page/Page column 42
[2]Journal of Medicinal Chemistry,1998,vol. 41,p. 3186 - 3201

22
[ 4524-93-0 ]
[ 145071-72-3 ]

Reference： [1]European Journal of Medicinal Chemistry,1992,vol. 27,p. 537 - 544

23
[ 5802-65-3 ]
[ 4524-93-0 ]

Reference： [1]Journal of the Chemical Society,1894,vol. 65,p. 104
Chemische Berichte,1893,vol. 26,p. 2249

24
[ 4524-93-0 ]
[ 668262-32-6 ]
[ 1354559-98-0 ]

Yield	Reaction Conditions	Operation in experiment
72%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 10h;	3 [5-CYANO-2-[3-(CYCLOPENTYLCARBONYL) BENZOYLLAMINO} BENZOIC] acid [TERT-BUTYL 5-CYANO-2- [ (3-IODOBENZOYL)] amino] benzoate (1.0 g, 2.23 mmol) was dissolved in 20 [ML] [OF CH2C12. HEXAMETHYLDITIN] (1.1 g, 3.35 mmol) and allylpalladium chloride dimer (73 mg, 0. 2 mmol) were then added and the mixture stirred at room temperature for 5 [HR.] The reaction was diluted with CH2Cl2 then washed with water. The organic solution was dried over [NA2SO4] and concentrated in vacuo. The remaining oil was purified via silica gel chromatography to give 670 mg (62%) of the desired tin compound. This product was subsequently dissolved in 15 [ML] [OF THF.] To this was added DIPEA [(1] mL), [PD2DBA3] (115 mg, . 125 mmol) and cyclopentanecarbonyl chloride (230 mg 1.73 [MMOL).] The reaction was then warmed to [60 °C AND] stirred for 10 additional hr. After cooling to room temperature the reaction was poured into 1 M HC1 (20 [ML)] and extracted with EtOAc (3 x 20 mL). The organic solution was dried over [NA2SO4] and concentrated in vacuo. The remaining residue was purified via silica gel chromatography, giving 415 mg [(72%)] of the desired ketone. The ketone was treated with [CH2CL2/TFA] and stirred for 10 additional hours. The solvent was removed in vacuo and the remaining solid was recrystalized from [MEOH] to give the title compound (329 mg, 91%) as a white solid. [1H NMR] (400 MHz, DMSO) 1.62-1. 67 [(M,] 4H), 1.73-1. 80 [(M,] 2H), 1. [92-1. 98 (M,] 2H), 3.90 (quint, 1H), 7.77 (t, 1H), 8. 11 (dd, 1H), [8.] 19 (d, [1H),] 8.27 (d, [1H), 8.] 41 (d, [1H),] [8.] 53 (s, 1H), 8.84 (d, 1H), 12.55 (s, 1H)

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/18414, 2004, A2 Location in patent: Page 83

25
[ 4524-93-0 ]
[ 18107-18-1 ]
[ 932-28-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: Cyclopentanecarboxylic acid chloride; diazomethyl-trimethyl-silane In tetrahydrofuran; hexanes at 0 - 20℃; for 12h; Stage #2: With hydrogenchloride In tetrahydrofuran; 1,4-dioxane at 24℃; for 2h;	A.6.1 Step 1: 2-CHLORO-1-CYCLOPENTYL-ETHANONE. Cyclopentanecarbonyl chloride (5.0 g, 0.038 mol) was dissolved in THF (100 mL) and cooled to 0 C. The solution was treated with a 2M solution of TMS-Diazomethane in hexanes (56.56 mL, 0.113 mol) over 10 min. The resulting yellow solution was allowed to stand at room temperature for 12 hours. The solution was then concentrated and the residue was dissolved in THF (100 mL) and treated slowly with a 4N HCI in Dioxane solution (28.28 mL, 0.113 MOL). The result was allowed to stir at 24 C for 2 hours. The solution was concentrated to an oil which was chromatographed on silica gel eluting with 5% EtOAc in Hexanes to give the intermediate depicted below (4.9 g, 88%) H NMR (CDC13) : 8 1.62-1. 98 (m, 8H), 3.12-3. 25 (M, 1H), 4.21 (s, 2H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/74270, 2004, A2 Location in patent: Page 39-40

26
[ 4524-93-0 ]
[ 754-05-2 ]
[ 50738-66-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	With aluminum (III) chloride In dichloromethane at -10℃; for 0.833333h;	H.1.1 A solution of cyclopentanecarbonyl chloride (10 g, 75 mmol) and AlCl3 (11.1 g, 83 mmol) in CH2Cl2 (100 mL) was cooled to -10° C. A solution of vinyltrimethylsilane (12 mL, 75 mmol) in CH2Cl2 (50 mL) was added drop wise over 30 minutes. The reaction was stirred for 20 additional minutes, and then poured over 200 g of ice. The layers were separated, and the aqueous layer was extracted with CH2Cl2. The organic layers were combined and washed with saturated NaHCO3. The organic was then dried over Na2SO4, the solids were filtered away, and the product was purified by distillation (7.17 g, 60%). 1H NMR (CDCl3) δ: 1.43-1.70 (m, 8H), 2.69-2.80 (m, 3H), 3.61 (t, J=6.57 Hz, 2H).

Reference： [1]Current Patent Assignee: PFIZER INC - US2005/176701, 2005, A1 Location in patent: Page/Page column 234

27
[ 856693-61-3 ]
[ 4524-93-0 ]
C₂₆H₂₄N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In nitromethane; dichloromethane at 20℃; for 24.25h;	321 To a stirred solution of aluminum chloride (0.49 g, 3.69 mmol, 10 equiv.) in methylene chloride (3 mL)-nitromethane (2 mL) at room temperature under nitrogen, was added cyclopentylcarbonyl chloride (0.45 mL, 3.69 mmol, 10 equiv.). The solution was stirred at room temperature for 15 min. The dihydroindazole template (0.12 g, 3.69 mmol, 1 equiv.) was added as a solid to the reaction mixture. After 24 h at room temperature, the reaction mixture was cooled to 0° C. and quenched with 10% HCl. The product precipitated out of solution and was collected by filtration (0.15 g, 97% yield). 1H NMR (DMSO-d6): δ 1.55 (m, 1H), 1.67 (m, 2H), 1.83 (m, 3H), 1.97 (m, 2H), 2.88 (dd, 2H), 3.26 (dd, 2H), 3.87 (s, 3H), 4.004 (m, 1H), 4.89 (s, 2H).7.62 (d, 1H), 8.09 (s, 1H), 8.51 (s, 1H), 8.91 (s, 1H), 11.91 (s, 1H); MS (ESI): m/e 425 (M+H)+.

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2005/143442, 2005, A1 Location in patent: Page/Page column 62; 97

28
[ 4524-93-0 ]
[ 851882-63-8 ]
cyclopentyl-{(S)-3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: Cyclopentanecarboxylic acid chloride; (S)-3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidine With triethylamine In dichloromethane at 0 - 20℃; Stage #2: With hydrogenchloride	34 Example 34 Cyclopentyl- { (S)-3- [3- (4-fluoro-phenyl)- [ 1, 2,4] oxadiazol-5-yl]-piperidin-1-yl}- methanone The compound was prepared following the procedure described in the Example 13, using cyclopentane-carbonyl chloride as the acyl chloride of choice and S-3-[3-(4- fluoro-phenyl)- [1, 2,4] oxadiazol-5-yl] -piperidine hydrochloride (prepared as described in the Example 12). Yield: 91 % (thick oil); [a] D20 = +95° (c=1.2, CHC13) ; LCMS (Tr): 7.41 min (Method A); MS (ES+) gave m/z : 344.2. 1H-NMR (CDCl3, 343 K, 300 MHz), 8 (ppm): 8.07 (dd, 2H); 7.15 (dd, 2H); 4.48 (m, 1H); 4.08 (m, 1H); 3.38 (m, 1H); 3.21-3. 07 (m, 2H); 2.96 (m, 1H); 2.36-2. 24 (m, 1H); 2.05-1. 51 (m, 11H).

Reference： [1]Current Patent Assignee: ADDEX THERAPEUTICS SA - WO2005/44797, 2005, A1 Location in patent: Page/Page column 72

29
[ 4524-93-0 ]
ethyl (S)-3-amino-3-phenyl-propionate hydrochloride [ No CAS ]
C₁₇H₂₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; triethylamine In dichloromethane at 0℃; for 2h;	A 10 mL rb flask equipped with a stir bar and septum was charged with 300 mg of ethyl (ri)-3 -amino-3 -phenylpropanoate hydrochloride (1.31 mmol, 1 equiv.), 16.0 mg of DMAP (0.131 mmol, 0.1 equiv.) and 419 pL ofNEt3 (3.00 mmol, 2.3 equiv.) dissolved in 1.1 mL of CH2CI2 at 0 °C. Then 175 pL of cyclopentanecarbonyl chloride (1.44 mmol, 1.1 equiv.) was added dropwise. After stirring at 0 °C for 2 h, the reaction mixture was quenched by addition of sat. NH4Cl solution, extracted with Et20 (3x) and dried over Na2S04.The crude product was purified on silica gel column using 10-20 % EA in hexanes as eluent affording 364 mg (96 %) of the product 48 as a clear oil which crystallizes to white solid.
	With sodium carbonate In dichloromethane; water; toluene at 20℃;	25.1 To a solution of (S) -3-amino-3-phenylpropanoic acid ethyl ester hydrochloride (84,5.0 g, 21.76 mmol) in H20 (50 mL), saturated Na2C03 (50 mL), DCM (50 mL) and toluene (20 mL) was added cyclopentylcarboxylic acid chloride (2.9 mL, 23.93 mmol). The reaction was stirred overnight at RT. The mixture was extracted with DCM and the organic layer was dried (MgS04), filtered and concentrated in vacuo. The residue containing 85a was redissolved in H2O (50 mL) and THF (50 mL) LiOH.H2O (2.73 g, 65.06 mmol) was added. After 3h, the mixture was washed with ether. The aqueous layer was acidified with 2N HCI and extracted with EtOAc. The organic layer was dried (MgS04), filtered and evaporated to afford 5.56 g (97%) of85b; ¹H NMR (CDC13) No. 1.5-1.65 (m, (m, 6H), 2.55 (t, 1H), 2.8-3.0 (qd, 2H), 5.4-5.5 (m, 1H), 6.4-6.45 (d, 1H), 7.2-7.45 (m, 5H).

Reference： [1]Current Patent Assignee: EMORY UNIVERSITY - WO2019/183133, 2019, A1 Location in patent: Page/Page column 48
[2]Current Patent Assignee: ROCHE HOLDING AG - WO2005/121145, 2005, A2 Location in patent: Page/Page column 154

30
[ 4524-93-0 ]
[ 879887-77-1 ]
2R-(N-1-cyclopentylcarbonylindolin-5-yl-N-4-chlorophenylsulfonyl)methylamino-4-methyl-pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; triethylamine In dichloromethane at 25℃; for 4h;	12 2R-(N-1-cyclopentylcarbonylindolin-5-yl-N-4-chlorophenylsulfonyl)methylamino-4-methyl-pentanamide EXAMPLE 12 2R-(N-1-cyclopentylcarbonylindolin-5-yl-N-4-chlorophenylsulfonyl)methylamino-4-methyl-pentanamide 2R-(N-indolin-5-yl-N-4-chlorophenylsulfonyl)methylamino-4-methyl-pentanamide (44 mg, 0.1 mmol), cyclopentylcarbonyl chloride (13 mg, 0.1 mmol), Et3N (21 μL, 0.15 mmol), 4-dimethylaminopyridine (12 mg, 0.1 mmol) and DCM (1 mL) were mixed and stirred at 25° C. for 4 h. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (3*10 mL). The combined organic layers were washed with brine (5 mL). Drying over Na2SO4, filtration and removal of solvent in vacuo gave an oil. Column chromatography (EtOAc:hexane:: 1:1) and removal of solvent in vacuo gave the title product, a white solid (53 mg, 100% yield): 1H NMR (CDCl3, 300 MHz): 8.18 (d, 1H), 7.66 (dd, 2H, J=9, 2), 7.45 (dd, 2H, J=9,2), 7.15-7.11 (m, 2H), 6.25 (s, 1H), 5.19 (s, 1H), 4.33 (d, 1H, J=16), 4.23 (d, 1H, J=16), 4.35-4.25 (m, 1H), 4.14 (t, 2H, J=7), 3.2-3.15 (m, 2H), 3.00-2.96 (m, 1H), 2.10-1.7 (m, 8H), 1.45-1.20 (m, 3H), 0.75 (d, 3H, J=7), 0.69 (d, 3H, J=7); MS (ES+): 554 (C27H34ClN3NaO4S, M++Na).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2006/63799, 2006, A1 Location in patent: Page/Page column 19

31
[ 98-82-8 ]
[ 4524-93-0 ]
[ 820259-88-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With aluminum (III) chloride In dichloromethane at -50 - -10℃; for 2h;	324 To a solution of cumene (16.4 g, 137 mmol) and aluminum chloride (21.9 g, 164 mmol) in dichloromethane (200 mL) was added cyclopentanecarbonyl chloride (20 g, 151 mmol) at -50°C (the inside temperature), and the mixture was stirred for two hours until the temperature reached - 10°C (the inside temperature). The reaction solution was poured into ice-cold water to separate the organic layer. The organic layer was washed with a 12 N sodium hydroxide solution and a saturated brine, and then dried over sodium sulfate. The solvent was distilled off under reduced pressure to obtain 22.5 g (yield 80%) of the title compound as oily matter. Oily matter. 1H-NMR (CDCl3) δ: 1.27 (6H, d, J = 6.9 Hz), 1.57-1.92 (8H, m), 2.96 (1H, septet, J = 6.9 Hz), 3.69 (1H, quartet, J = 7.8 Hz), 7.29 (2H, d, J = 8.4 Hz), 7.90 (2H, d, J = 8.4 Hz).
	With aluminum (III) chloride In dichloromethane at 0℃; for 2h; Sealed tube; Inert atmosphere;	Typical Procedure for Transformation of Arenes 1 into 5-Alkyl-1-aryltetrazoles 3: General procedure: To a solution ofcumene 1A (1.0 mmol, 120.0 mg) in CH2Cl2 (2.0 mL) in a 30 mL sealed tube was added acetyl chloride(1.2 mmol, 85.4 μL) at 0 °C. After flash with argon gas, the mixture was stirred for a few minutes.Anhydrous AlCl3 (1.2 mmol, 161.0 mg) was added and the obtained mixture was stirred for 2 h at 0 °C.Then, the reaction mixture was quenched with cooled water (1.0 mL) and stirred for 0.5 h. Afterremoval of the solvent under reduced pressure, MeOH (3.0 mL), NH2OHHCl (1.5 mmol, 107.0 mg), andK2CO3 (1.5 mmol, 207.0 mg) were added. After flash with argon gas, the obtained mixture was stirredfor 16 h at rt. After removal of the solvent under reduced pressure, toluene (3.0 mL), DPPA (2.5 mmol,0.54 mL), and DBU (3.5 mmol, 0.53 mL) were added to the residue. After flash with argon gas, themixture was warmed at 120 °C for 16 h. The mixture was cooled to rt and then, sat. NaHCO3 aq. (15.0mL) was added. The mixture was filtered through Celite, and the filtrate was extracted with AcOEt(20.0 mL ×3). The organic layer was dried over Na2SO4. After removal of the solvent under reducedpressure, the residue was purified by short column chromatography on silica gel (n-hexane/AcOEt,3:1-1:3) to afford 1-(4’-isopropylphenyl)-5-methyl-1H-tetrazole 3Aa in 60% yield (121.1 mg).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1637527, 2006, A1 Location in patent: Page/Page column 110
[2]Shibasaki, Kaho; Togo, Hideo [Heterocycles, 2020, vol. 100, # 11, p. 1816 - 1830]

32
[ 4524-93-0 ]
[ 6332-56-5 ]
cyclopentanecarboxylic Acid (2-Hydroxypyridin-3-yl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With NMM; In ethanol; dichloromethane; acetonitrile;	Preparation of Intermediate Cyclopentanecarboxylic Acid (2-Hydroxypyridin-3-yl)amide A sample of 10% Pd on C (0.40 g) was added to a solution of <strong>[6332-56-5]2-hydroxy-3-nitropyridine</strong> (3.52 g, 25.0 mmol, 1 equiv) in EtOH. The reaction mixture was stirred at room temperature under H2 atmosphere (balloon) overnight and then was filtered through Celite. The filtrate was concentrated under reduced pressure. The residue was dissolved in CH3CN (100 mL), cooled to 0 C., and cyclopentanecarbonyl chloride (25 mmol, 3.04 mL, 1 equiv) and NMM (2.75 mL, 25 mmol, 1 equiv) were added sequentially. The resulting mixture was stirred at 0 C. for 20 min, then was partitioned between water (400 mL) and 10% CH3OH in CH2Cl2 (2*400 mL). The organic layers were dried over Na2SO4, concentrated, and the resulting residue recrystallized from CH2Cl2/hexanes to afford the title intermediate as a off-white solid (3.36 g, 65%); mp=242-243 C.; IR (cm-1) 3263, 1644, 1605, 1521, 1199; 1H NMR (DMSO-d6) delta 1.51-1.57 (m, 2H), 1.60-1.72 (m, 4H), 1.79-1.88 (m, 2H), 2.98-3.08 (m, 1H), 6.20 (t, 1H, J=6.9), 7.08 (d, 1H, J=6.6), 8.23 (d, 1H, J=7.5), 9.02 (s, br. 1H), 11.95 (s, br. 1H); Anal. C11H14N2O2: C, H, N.

Reference： [1]Patent: US2001/47006,2001,A1

33
[ 4524-93-0 ]
[ 100-68-5 ]
[ 180048-75-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	In chloroform; water	21.1 Step 1 Step 1 Cyclopentyl-(4-(methylthio)phenyl)methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCl3 at 0° C. was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2 h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCl3 (3*50 mL). The combined aqueous layers were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the title ketone (93%). 1 H NMR (CD3 COCD3) δ 7.94 (d, 2H), 7.36 (d, 2H), 3.79 (q, 1H), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H).
93%	In chloroform; water	21.1 Step 1: Step 1: Cyclopentyl-(4-(methylthio)phenyl)methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCl3 at 0° C. was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2 h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCl3 (3*50 mL). The combined aqueous layers were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the title ketone (93%). 1 H NMR (CD3 COCD3) δ 7.94 (d, 2H), 7.36 (d, 2H), 3.79 (q, 1H), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H).
93%	In chloroform; water	21.1 Step 1 Step 1 Cyclopentyl-(4-(methylthio)phenyl)methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCl3 at 0° C. was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2 h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCl3 (3*50 mL). The combined aqueous layers were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the title ketone (93%). 1 H NMR (CD3 COCD3) ⅆ 7.94 (d, 2H), 7.36 (d, 2H), 3.79 (q, 1H), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H).

93%	In chloroform; water	21.1 Step 1: Step 1: Cyclopentyl-(4-(methylthio)phenyl)methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCl3 at 0 °C was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCl3 (3 x 50 mL). The combined aqueous layers were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the title ketone (93%). 1H NMR (CD3COCD3) ∂ 7.94 (d, 2H), 7.36 (d, 2H), 3.79 (q, 1H), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H).
93%	In chloroform; water	10.1 Cyclopentyl-(4-(methylthio)phenyl)-methanone Step 1 Cyclopentyl-(4-(methylthio)phenyl)-methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCl3 at 0° C. was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2 h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCl3 (3*50 mL). The combined aqueous layers were dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the title ketone (93%). 1H NMR (acetone-d6, 400 MHz) 7.94 (d, 2H, J=8.7 Hz), 7.36 (d, 2H, J=8.7 Hz), 3.79 (q, 1H), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5981576, 1999, A
[2]Current Patent Assignee: MERCK & CO INC - US6020343, 2000, A
[3]Current Patent Assignee: MERCK & CO INC - US5698584, 1997, A Current Patent Assignee: MERCK & CO INC - US5789413, 1998, A
[4]Current Patent Assignee: MERCK & CO INC - EP882016, 2000, B1
[5]Current Patent Assignee: MERCK & CO INC - US6222048, 2001, B1

34
[ 4524-93-0 ]
[ 919118-54-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 4-piperidone hydrochloride With potassium carbonate In dichloromethane for 0.0833333h; Stage #2: Cyclopentanecarboxylic acid chloride In dichloromethane at 20℃; for 16h;	Preparation of l-Cyclopentanecarbonyl-4-piperidone C11H17NO2, MW: 195.2611 EPO To a solution of 4-piperidonehydrochloride monohydrate (750 mg, 4.88 mmol) in DCM (25 ml), was added potassium carbonate (2.02 g, 14.65 mmol). After 5 minutes stirring, the addition of cyclopentanecarbonyl chloride (1.29 g, 9.76 mmol) proceeded at room temperature and stirring continued for a further 16 hours. The reaction was then quenched with IM NaOH (15 ml) and then extracted with DCM (3 x 20 ml). The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The obtained yellow oil then underwent purification by flash chromatography (eluant; 1:1 hexane : ethyl acetate) and the relevant fractions were concentrated in vacuo to provide the title compound as a transparent oil (769 mg, 81%). 1H NMR (300 MHz, CDCl3): δ 1.47-1.60 (2H, m, 2 x CH), 1.61-1.73 (2H, m, 2 x CH)5 1.74-1.85 (4H, m5 4 x CH), 2.40 (4H3 1, J = 6.3 Hz5 4 x CH), 2.85-2.96 (IH5 pent, J = 7.8, 8.I5 15.9 Hz5 CH), 3.73-3.84 ppm (4H5 m, 4 x CH). LCMS: M+H: 196.31 HPLC: 100% (2.624 min, isocratic 90% acetonitrile, 10% water at 1 ml/min).

Reference： [1]Current Patent Assignee: Oxford University Innovation (in: Oxford University); UNIVERSITY OF OXFORD - WO2007/3934, 2007, A2 Location in patent: Page/Page column 155-156

35
[ 4524-93-0 ]
[ 51175-79-2 ]
[ 1057478-41-7 ]

Reference： [1]Russian Journal of Organic Chemistry,2007,vol. 43,p. 1628 - 1631

36
[ 4524-93-0 ]
[ 62266-82-4 ]
[ 952288-83-4 ]

Reference： [1]Heterocycles,2007,vol. 71,p. 2041 - 2047

37
[ 4524-93-0 ]
[ 2756-85-6 ]
[ 944281-66-7 ]

Yield	Reaction Conditions	Operation in experiment
42%	Stage #1: Cyclopentanecarboxylic acid chloride; 1-aminocyclohexane carboxylic acid With sodium carbonate In water; ethyl acetate at 0 - 20℃; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	154 1.98 g (15 mmol) of cyclopentanecarbonyl chloride was added to a solution of 2.16 g (15 mmol) of 1-aminocyclohexanecarboxylic acid and 4.8 g (45 mmol) of sodium carbonate in 50 ml of ethyl acetate-50 ml of water under ice-cooling. After the mixture was stirred at room temperature overnight, ethyl acetate was added thereto, and the mixture was washed with a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium bicarbonate solution and then saturated brine. After the obtained organic layer was washed with saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, methylene chloride was added thereto, and under ice-cooling, 1.59 g (8.3 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added. After the mixture was stirred at room temperature overnight, the reaction solution was concentrated under reduced pressure, ethyl acetate was added thereto, and the mixture was successively washed with water, a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, followed by drying with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 1.41 g (42%) of the title compound.1H-NMR (CDCl3, δ): 1.53-1.65 (5H, m), 1.67-1.76 (4H, m), 1.86-1.95 (8H, m), 2.80-2.89 (2H, m)
42%	Stage #1: Cyclopentanecarboxylic acid chloride; 1-aminocyclohexane carboxylic acid With sodium carbonate In water; ethyl acetate at 20℃; Stage #2: With potassium hydrogensulfate In water; ethyl acetate Stage #3: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	154 REFERENCE EXAMPLE 1542-Cyclopentyl-3-oxa-1-azaspiro[4.5]dec-1-en-4-one 1.98 g (15 mmol) of cyclopentanecarbonyl chloride was added to a solution of 2.16 g (15 mmol) of 1-aminocyclohexanecarboxylic acid and 4.8 g (45 mmol) of sodium carbonate in 50 ml of ethyl acetate-50 ml of water under ice-cooling. After the mixture was stirred at room temperature overnight, ethyl acetate was added thereto, and the mixture was washed with a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium bicarbonate solution and then saturated brine. After the obtained organic layer was washed with saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, methylene chloride was added thereto, and under ice-cooling, 1.59 g (8.3 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added. After the mixture was stirred at room temperature overnight, under reduced pressure, the reaction solution was concentrated, ethyl acetate was added thereto, and the mixture was successively washed with water, a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, followed by drying with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 1.41 g (42%) of the title compound.1H-NMR (CDCl3, δ): 1.53-1.65 (5H, m), 1.67-1.76 (4H, m), 1.86-1.95 (8H, m), 2.80-2.89 (2H, m)
42%	Stage #1: Cyclopentanecarboxylic acid chloride; 1-aminocyclohexane carboxylic acid With sodium carbonate In water; ethyl acetate at 20℃; Stage #2: With potassium hydrogensulfate In water Stage #3: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	22 2-Cyclopentyl-3-oxa-1-azaspiro[4.5]dec-1-en-4-one Example 22 2-Cyclopentyl-3-oxa-1-azaspiro[4.5]dec-1-en-4-one 1.98 g (15 mmol) of cyclopentanecarbonyl chloride was added to a solution of 2.16 g (15 mmol) of 1-aminocyclohexanecarboxylic acid and 4.8 g (45 mmol) of sodium carbonate in 50 ml of ethyl acetate-50 ml of water under ice-cooling. After the mixture was stirred at room temperature overnight, ethyl acetate was added thereto, and the mixture was washed with a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium bicarbonate solution and then saturated brine. After the obtained organic layer was washed with saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, methylene chloride was added thereto, and 1.59 g (8.3 mmol) of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride was added under ice-cooling. After the mixture was stirred at room temperature overnight, the reaction solution was concentrated under reduced pressure, ethyl acetate was added thereto, and the mixture was successively washed with water, a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, followed by drying with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 1.41 g (42%) of the title compound. 1H-NMR (CDCl3, δ): 1.53-1.65 (5H, m), 1.67-1.76 (4H, m), 1.86-1.95 (8H, m), 2.80-2.89 (2H, m)

Multi-step reaction with 2 steps 1: sodium carbonate / water; ethyl acetate / 0 - 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 - 20 °C

Reference： [1]Current Patent Assignee: SEIKAGAKU CORPORATION - US2009/111983, 2009, A1 Location in patent: Page/Page column 56
[2]Current Patent Assignee: SEIKAGAKU CORPORATION - US2009/137799, 2009, A1 Location in patent: Page/Page column 56
[3]Current Patent Assignee: SEIKAGAKU CORPORATION - EP1975162, 2008, A1 Location in patent: Page/Page column 76
[4]Current Patent Assignee: SEIKAGAKU CORPORATION - EP1972615, 2008, A1

38
[ 4524-93-0 ]
[ 2199-43-1 ]
[ 1092375-54-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Cyclopentanecarboxylic acid chloride With aluminum (III) chloride at 0 - 5℃; for 0.25h; Inert atmosphere; Stage #2: ethyl 1H-pyrrole-2-carboxylate In dichloromethane at 0 - 20℃; for 4h;	A1 4-Cyclopentanecarbonyl-1-H-pyrrole-2-carboxylic acid ethyl ester (A1-I); A mixture of cyclopentanecarbonyl chloride and aluminum chloride in dry DCM were stirred in an inert atmosphere at 0-5° C. for 15 minutes. To this, a solution of 1H-pyrrole-2-carboxylic acid ethyl ester in dry DCM was added drop wise under stirring at 0-5° C., stirred further at room temperature for 4 hrs. After completion of reaction, the reaction mixture was poured into ice water and extracted with DCM, DCM layer was washed with 1N NaOH followed by water and brine. The organic layer was dried over anhydrous sodium sulfate and was evaporated to get 4-Cyclopentanecarbonyl-1-H-pyrrole-2-carboxylic acid ethyl ester (A1-I).1H NMR (400 MHz, CDCl3): δ 1.38 (t, J=7.2 Hz, 3H), 1.64-1.66 (m, 2H), 1.71-1.75 (m, 2H), 1.88-1.93 (m, 4H), 3.40-3.46 (m, 1H), 4.35 (q, J=7.2 Hz, 2H), 7.30-7.31 (m, 1H), 7.54-7.55(m, 1H).
	Stage #1: Cyclopentanecarboxylic acid chloride With aluminum (III) chloride In dichloromethane at 0 - 5℃; for 0.25h; Stage #2: ethyl 1H-pyrrole-2-carboxylate In dichloromethane at 0 - 20℃; for 4h; Stage #3: With sodium hydroxide; water In dichloromethane	A1 Example (Al): 4-Cyclopentylmethyl-l~(2,4-difluoro-benzyI)-lH-pyrrole-2- carboxylic acid (5-chloro-thiazol-2-yl)-amide; 4-CyclopentanecarbonyI-l-H-pyrrole-2-carboxylic acid ethyl ester (Al-I):A mixture of cyclopentanecarbonyl chloride and aluminum chloride in dry DCM were stirred in an inert atmosphere at 0-5 0C for 15 minutes. To this, a solution of IH- pyrrole-2-carboxylic acid ethyl ester in dry DCM was added drop wise under stirring at 0-5 °C, stirred further at room temperature for 4 hrs. After completion of reaction, the reaction mixture was poured into ice water and extracted with DCM, DCM layer was washed with IN NaOH followed by water and brine. The organic layer was dried over anhydrous sodium sulfate and was evaporated to get 4-Cyclopentanecarbonyl-l-H- pyrrole-2-carboxylic acid ethyl ester (Al-I).1H NMR (400 MHz, CDCl3): δ 1.38 (t, J = 7.2 Hz, 3H), 1.64-1.66 (m, 2H), 1.71-1.75 (m, 2H), 1.88-1.93 (m, 4H), 3.40-3.46 (m, IH)5 4.35 (q, J = 7.2 Hz, 2H), 7.30-7.31 (m, IH), 7.54-7.55(m, IH).

Reference： [1]Current Patent Assignee: EUROFINS SCIENTIFIC SA - US2010/292143, 2010, A1 Location in patent: Page/Page column 14
[2]Current Patent Assignee: EUROFINS SCIENTIFIC SA - WO2008/149382, 2008, A1 Location in patent: Page/Page column 33

39
4-(4-methylphenyl)-piperazine dihydrochloride [ No CAS ]
[ 4524-93-0 ]
[ 497-19-8 ]
[ 1159929-64-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 4-(4-methylphenyl)-piperazine dihydrochloride; Cyclopentanecarboxylic acid chloride With triethylamine In DCM at 0 - 20℃; for 16h; Stage #2: sodium carbonate In DCM; water	40 1-Methyl-4-[(1-[4-(4-methylphenyl)piperazin-1-yl]carbonyl}cyclopentyl)-methyl]piperazine Example 40 1-Methyl-4-[(1-[4-(4-methylphenyl)piperazin-1-yl]carbonyl}cyclopentyl)-methyl]piperazine 4-Methylphenyl piperazine dihydrochloride (4.20 g, 16.9 mmol) and NEt3 (7.0 mL, 50.2 mmol) were dissolved in DCM (125 mL) at 0° C. Cyclopentanecarbonyl chloride (2.0 mL, 16.5 mmol) was added and the reaction mixture was allowed to warm to room temperature over 16 hours. The reaction mixture was washed with 1M aq Na2CO3 solution (3*100 mL), dried (MgSO4) and concentrated in vacuo to give cyclopentanecarbonyl 4-(methyl)phenyl piperazine (4.42 g, 98%) as a pale brown oil which was used without further purification. Analytical LCMS: purity 100% (System C, RT=2.10 min), ES+: 273.4 [MH]+.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US2009/281087, 2009, A1 Location in patent: Page/Page column 24

40
[ 4524-93-0 ]
4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate [ No CAS ]
[ 1196486-28-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	147 Example 147Cyclopentyl-{4-[4-(4-ethoxy-2-fluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone; Cyclopentanecarbonyl chloride (10 mg, 0.078 mmol) was added to a mixture of 4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 29; 28 mg, 0.078 mmol), and diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature overnight. Water was added to quench the reaction and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate), filtered, evaporated and purified by flash chromatography on silica gel, eluting with 4% methanol/dichloromethane to give cyclopentyl-{4-[4-(4-ethoxy-2-fluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone (31 mg, 87%) as a white solid. Mass spectrum MH+=454.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2009/286812, 2009, A1 Location in patent: Page/Page column 69

41
[ 4524-93-0 ]
[ 1159317-82-4 ]
[ 1159317-84-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With piperidine; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	5A Under argon and at 0° C., N,N-diisopropylethylamine (1.2 eq.) and the appropriate carbamoyl chloride or carbonyl chloride (1.2 eq.) are added dropwise to a solution of the piperidine in dichloromethane (2.5 ml/mmol). The reaction mixture is stirred at RT. After addition of water and phase separation, the organic phase is washed three times with water and once with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. 5.2 g (14.0 mmol) of ethyl 5-(4-ethylphenyl)piperidine-3-carboxylate and 2.1 g (2.1 mmol, 1.2 eq.) of cyclopentanecarbonyl chloride were reacted according to General Method 3A. Yield: 4.8 g (96% of theory)LC-MS (Method 4B): Rt=4.04 min and 4.14 min (cis/trans isomers); MS (ESIpos): m/z=358 [M+H]+.

Reference： [1]Current Patent Assignee: BAYER AG - US2012/46268, 2012, A1 Location in patent: Page/Page column 21; 22

42
[ 4524-93-0 ]
[ 80947-25-7 ]
[ 1116652-01-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine; at 60.0℃; for 1.5h;	In brief, compound 9 was dissolved in pyridine (1 mmol/3 mL) and the appropriate acid chloride (1.3 eq) was added. The reaction was stirred at 60 0C for 90 minutes. After the reaction was completed, pyridine was evaporated. The product was purified by column chromatography [Chang, L. C. W. et al. 2,4,6-Trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists, J Med. Chem. 2004, 47, 6529-6540].N-(2-chloroquinoIin-4-yl)cyclopentanecarboxamide (ll)Scale: 1.6 mmol. Eluent for column chromatography was 5% MeOH in DCM. Yield: 0.34 g (78%). 1H NMR (CDCl3) delta 1.58-2.18 (m, 8H, 4CH2), 2.81-2.98 (m, IH,CH), 7.53-7.61 (m, IH, Ar), 7.68-7.76 (m, 2H, Ar), 7.95-8.03 (m, 2H, Ar, NH), 8.42 (s,IH, Ar). 13C NMR (CDCl3) (526.18, 30.72, 47.43, 91.47, 94.32, 111.33, 118.94, 126.86,130.04, 130.65, 142.41, 148.26, 152.24, 175.28.

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 926 - 931
[2]Patent: WO2010/20981,2010,A1 .Location in patent: Page/Page column 30-31

43
[ 4524-93-0 ]
[ 36825-35-1 ]
[ 1116652-00-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	With pyridine; at 115.0℃; for 2.0h;	In brief, compound 5 (0.32 g, 1.40 mmol) was dissolved in pyridine (5 mL) and cyclopenthanecarbonyl chloride (1.3 eq) was added. The reaction stirred at 115 0C for 2 hours. After the reaction was completed, pyridine was evaporated. The product was purified by column chromatography, eluent 5% MeOH in DCM. The product was crystallized from MeOH to give white crystals. Yield: 0.35 g (79%). MS (ESI) m/z: 319.9 [M+Hf1, [M-H]+1. 1H NMR (CDCl3) delta 1.64-2.07 (m, 8H, 4CH2), 2.53-3.00 (m, IH, CH), 7.54-7.62 (m, IH, Ar), 7.69-7.79 (m, 2H, Ai'), 7.92 (bs, IH, NH), 7.99-8.08 (m, IH, Ar), 8.43 (s, IH, Ar). 13C NMR (CDCl3) delta 25.96, 30.51, 47.2, 114.51, 118.85, 126.76, 129.89, 130.40, 141.56, 143.17, 148.63, 175.07 [Chang, L. C. W. et al. 2,4,6- Trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists, J. Med. Chem. 2004, 47, 6529-6540].

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 926 - 931
[2]Patent: WO2010/20981,2010,A1 .Location in patent: Page/Page column 30; 1/2

44
[ 4524-93-0 ]
[ 2835-81-6 ]
[ 252678-53-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 2-aminobutanoic acid With chloro-trimethyl-silane; triethylamine In dichloromethane at 0 - 40℃; for 2h; Stage #2: Cyclopentanecarboxylic acid chloride In dichloromethane at -10 - 20℃; for 3h;	3A 35 g (339 mmol) 2-aminobutanoic acid and 75.6 g (747 mmol) triethylamine are suspended in 300 ml of dichloromethane and stirred at 0°C. 81 g (747 mmol) chlorotrimethylsilane are added dropwise, then the mixture is stirred for 1 hour at room temperature and for 1 hour at 40°C. After cooling down to-10°C, 45 g (339 mmol) cyclopentanecarbonyl chloride are added slowly. The reaction mixture is stirred for 2 hours at-10°C and then for 1 hour at room temperature. At 0°C, 50 ml of water are added. The mixture is diluted with water and dichloromethane, filtered and the solid product washed with water/dichloromethane 9: 1, toluene and diethylether. Yield 52.4 g (77%) 'H-NMR (DMSO-d6, 300 MHz): 8 = 0.9 (t, 3H), 1.6 (m, 10H), 2.6 (m, 1H), 4,1 (m, 2H), 7.9 (d, 1H), 12.4 (s, 1H) ppm.

Reference： [1]Current Patent Assignee: BAYER AG - WO2003/97645, 2003, A1 Location in patent: Page/Page column 27

45
[ 4524-93-0 ]
[ 100945-15-1 ]
[ 705295-07-4 ]

Yield	Reaction Conditions	Operation in experiment
15%	Stage #1: N-(benzyloxycarbonyl)phosphonoglycine trimethyl ester With hydrogen In DMF (N,N-dimethyl-formamide) for 1h; Stage #2: Cyclopentanecarboxylic acid chloride With dmap; triethylamine In DMF (N,N-dimethyl-formamide) at 0 - 20℃;	85 Example 85; (CYCLOPENTANECARBONYL-AMINO)-(DIMETHOXY-PHOSPHORYL)-ACETIC ACID METHYL ESTER An oven dried 500 ml Parr flask was equipped with a magnetic stirring bar, continuously flushed with nitrogen gas, and charged with the trimester (11.0 g, 33.2 mmol), anhydrous DMF (100 ml), and 10% Pd/C (500 mg). The flask was fitted into a Parr hydrogenation apparatus and the mixture was treated with hydrogen gas at 50 psi for sixty minutes. The reaction was filtered through Celite and transferred to a 250 ml round-bottomed flask. The reaction was diluted with anhydrous triethylamine (9.5 ml) and DMAP (810 mg). The flask was transferred to a brine-ice bath and cooled to 0 C for fifteen minutes. Cyclopentanecarbonyl chloride (5.28 g, 39.84 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The reaction was concentrated in vacuo and diluted with ethyl acetate (250 ml), washed with 1. OM HCl (20 ml), water (2 X 150 ml), a saturated solution on sodium bicarbonate (2 X 60 ml), water (2 X 200 ml), and brine (2 X 200 ml). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The product was triturated with 1,2-dimethoxyethane, filtered and concentrated in vacuo. The product was isolated as a tan colored solid, 1.44 g, 15% yield, M. P. = 90.1-90. 9 C.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2004/50613, 2004, A2 Location in patent: Page 96-97

46
[ 4524-93-0 ]
[ 1004546-45-5 ]
[ 1050676-85-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: Cyclopentanecarboxylic acid chloride; 2',3',4',9'-tetrahydro-N,N-dimethyl-4-butyl-spiro[cyclohexane-1,1'(1'H)-pyrido[3,4-b]indol]-4-amine In dichloromethane at 20℃; for 2.25h; Inert atmosphere; Stage #2: With sodium hydroxide In dichloromethane; water for 1h; Inert atmosphere;	AA-11 Example AA-11; 2',3',4',9'-Tetrahydro-N,N-dimethyl-4-butyl-2'-cyclopentylcarbonyl-spiro[cyclohexane-1,1'(1'H)-pyrido[3,4-b]indol]-4-amine, 2-hydroxy-1,2,3-propanetricarboxylate (2:1) less polar diastereoisomerCyclopentanecarboxylic acid chloride (0.215 ml, 234 mg, 1.77 mmol) was dissolved in abs. dichloromethane (5 ml), under argon, and the less polar spiroamine (less polar free base of AA-9, 200 mg, 0.59 mmol), dissolved in dichloromethane (15 ml), was added, at room temperature, in the course of 45 min. Stirring was carried out for a further 1.5 h at room temperature. For working up, water (10 ml) and 1N sodium hydroxide solution (5 ml) were added to the colorless mixture, and stirring was carried out for 1 h. The phases were separated. The aqueous phase was extracted with dichloromethane (20 ml). The combined organic phases were washed with water (20 ml), dried and concentrated. A beige-colored oil (325 mg) was thereby obtained and was separated by chromatography [silica gel 60 (40 g); ethyl acetate (350 ml)]. The amide was isolated in the form of a colorless hygroscopic solid in a yield of 87% (222 mg).

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - US2010/48554, 2010, A1 Location in patent: Page/Page column 21

47
[ 4524-93-0 ]
[ 17220-38-1 ]
[ 1217268-69-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1148 - 1152

48
[ 4524-93-0 ]
methyl 4-(isobutylamino)-3-nitrobenzoate [ No CAS ]
[ 942289-38-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl 4-(isobutylamino)-3-nitrobenzoate With hydrogenchloride; hydrogen In methanol at 50℃; for 1.5h; Stage #2: Cyclopentanecarboxylic acid chloride With triethylamine In 1,1-dichloroethane at 20℃; for 12h;	2; 3 A 1 L Parr vessel, equipped with a heater, was charged with methyl 4-(isobutylamino)-3-nitrobenzoate (50.0 g, 198.2 mmol), Pd/C (10%, 5.0 g) mixed with cone. HCI (16.5 mL), and MeOH (500 mL). The mixture was hydrogenated in Parr apparatus at 50 0C and 40 psi for 1.5 h. Then the mixture was cooled to RT and the catalyst was removed by filtration through celite. Some product was left as a solid on celite cake. This product was dissolved by washing the cake with DCM/MeOH 1 :1 mixture (5x200 mL). The combined filtrate was evaporated and the residue dried under vacuum to give 50.6 g (99%) of pure product as a white solid. LCMS (M+H): 223.4; 1H NMR (300 MHz, DMSO-d6): δ 9.6 (br., 2H), 7.72 (m, 2H), 6.76 (d, J = 8.64 Hz, 1 H), 6.3 (br., 1 H), 3.78 (s, 3H), 2.96 (d, J = 6.96 Hz, 2H), 1.92 (m, 1 H), 0.98 (d, J = 6.6 Hz, 6H). Intermediate 3Synthesis of methyl 3-f(cvclopentylcarbonyl)amino1-4-(isobutylamino)benzoate.A 1 L RB flask, equipped with a magnetic stirring bar, nitrogen gas inlet and septum, was charged with methyl 3-amino-4-(isobutylamino)benzoate hydrochloride (25 g, 96.7 mmol), dichloroethane (220 mL) and triethylamine (29.6 mL, 213 mmol). Then cyclopentanecarbonyl chloride (14.10 g, 106 mmol) was added dropwise via syringe. The mixture was stirring at RT for 12 h, then quenched with 200 mL of sat. NaHCO3, and diluted with 500 mL of DCM. The organic layer was separated and the aqueous layer was extracted with DCM (2x100 mL). The combined organic fractions were dried over Na2SO4 and evaporated to give 32.8 g (quantitative) of pure product as a white solid. LCMS (M+H): 319.4; 1H NMR (300 MHz, CDCI3): δ 7.83 (d, J = 8.67 Hz, 1 H), 7.72 (s, 1 H), 6.96 (s, 1 H), 6.67 (d, J = 8.85 Hz, 1 H), 4.67 (br., 1 H), 3.84 (s, 3H), 2.98 (m, 2H), 2.78 (m, 1 H), 1.58-2.01 (m, 10H), 1.00 (d, J = 6.78 Hz, 6H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2007/69053, 2007, A1 Location in patent: Page/Page column 20

49
[ 4524-93-0 ]
[ 59557-92-5 ]
[ 1242077-77-5 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 5994 - 6000

50
[ 4524-93-0 ]
[ 6148-64-7 ]
[ 24922-00-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine; magnesium chloride; In acetonitrile; at 0℃; for 4h;	Potassium monoethyl malonate (20 g, 118 mmol, 2.05 equiv.) is dispersed in anhydrous acetonitrile (200 ml) and magnesium chloride (13.64 g, 143 mmol, 2.5 equiv.) and triethylamine (18.38 ml, 132 mmol, 2.3 equiv.) are added at O C. After 10 min, cyclopentanecarbonyl chloride (6.97 ml, 57.3 mmol) is added and the orange suspension is stirred at 0 0C. After 4 h, the reaction mixture is concentrated in vacuo and the residue is partitioned between DCM and aqueous 0.5 M KHSO4 solution. The organic layer is washed with aqueous 0.5 M KHSO4 solution and brine, dried over Na2SO4 and concentrated to dryness to afford a brown oil. The oily residue is purified by flash column chromatography (3-30% EtOAc in heptane) to give 8.12 g (77%) of the product as an orange oil. 1H-NMR (400 MHz, CDCI3): delta (ppm) 1.28 (3H, t), 1.54-1.73 (4H, m), 1.73-1.90 (4H, m), 2.95-3.04 (1 H, m), 3.49 (2H, s), 4.20 (2H, q).

Reference： [1]Patent: WO2010/139483,2010,A1 .Location in patent: Page/Page column 67-68

51
[ 4524-93-0 ]
[ 185614-40-8 ]
[ 1196886-98-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: ethyl 1-(methoxymethyl)-4-nitro-1H-imidazole-2-carboxylate With hydrogen In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; Stage #2: Cyclopentanecarboxylic acid chloride With triethylamine at 0 - 20℃;	III-73.1 To a solution of ethyl l-(methoxymethyl)-4-nitro-lH-imidazole-2-carboxylate (3 g, 13.10 mmol) in THF (20 mL) under N2 was added Pd/C (0.5 g). To this was introduced hydrogen and the mixture was stirred for 3 hrs at room temperature. The solids were filtered out and washed with 10 mL of THF. To the combined filtrates was added TEA (2.6 g, 25.74 mmol) and cyclopentanecarbonyl chloride (2.6 g, 19.55 mmol) in dropwise at 00C. The resulting solution was stirred for overnight at room temperature. The resulting mixture was concentrated under vacuum and the residue was dissolved in 150 mL of ethyl acetate. The resulting solution was washed with 2 x 100 mL of water and 30 mL of brine. The mixture was dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified on a silica gel column with ethyl acetate/petroleum ether (1 :5) to give 3.3 g (85%) of ethyl 4-(cyclopentanecarboxamido)- 1 -(methoxymethyl)- 1 H-imidazole-2- carboxylate as white oil.

Reference： [1]Current Patent Assignee: PONIARD PHARMACEUTICALS, INC. - WO2009/139834, 2009, A1 Location in patent: Page/Page column 146

52
[ 4524-93-0 ]
[ 18650-38-9 ]
C₁₃H₂₁NO₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2711 - 2714

53
[ 4524-93-0 ]
[ 4498-68-4 ]
[ 1325682-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In toluene; at 110℃; for 5h;	Cyclopentanecarboxylic acid (0.525 mmol) dissolved in SOCl2 (1 mL) was stirred at 100 C for 1 h. After cooling, the excess SOCl2 was removed in vacuo, and the residue was dissolved in cold anhydrous toluene (3-4 mL). To this solution, a mixture of <strong>[4498-68-4]1H-indazole-3-carboxylic acid ethyl ester</strong> 432 (0.525 mmol) and Et3N (0.577 mmol) in toluene anhydrous (3 mL) was added, and the suspension was stirred at 110 C for 5 h. After cooling, the precipitate was filtered off, the solvent was evaporated in vacuo, cold water (15 mL) was added, and resulting mixture was neutralized with 0.5 N NaOH and extracted with CH2Cl2 (3 × 15 mL). Evaporation of the solvent resulted in the final compound 6d. Yield = 86%; oil; 1H NMR (CDCl3) delta 1.55 (t, 3H, OCH2CH3, J = 7.2 Hz), 1.75-1.85 (m, 4H, cC5H9), 1.95-2.05 (m, 2H, cC5H9), 2.10-2.20 (m, 2H, cC5H9), 4.20-4.30 (m, 1H, cC5H9), 4.60 (q, 2H, OCH2CH3, J = 7.2 Hz), 7.50 (t, 1H, Ar, J = 8.0 Hz), 7.60 (t, 1H, Ar, J = 8.4 Hz), 8.25 (d, 1H, Ar, J = 8.0 Hz), 8.50 (d, 1H, Ar, J = 8.4 Hz). Anal. (C16H18N2O3) C, H, N.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 4460 - 4472

54
[ 4524-93-0 ]
cis-{3-amino-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(morpholin-4-yl)methanone hydrochloride [ No CAS ]
cis-N-{1-(morpholin-4-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine In dichloromethane at 0 - 20℃;	166 212 μl of triethylamine (1.52 mmol) and 18.6 mg of DMAP (0.152 mmol) were added to a solution of the compound from Example 57A (200 mg, 0.508 mmol) in dichloromethane (12 ml), and 93 μl of cyclopentanecarbonyl chloride (0.762 mmol) were then added at 0° C. The reaction mixture was warmed to RT and stirred overnight. The reaction solution was washed with aqueous 1 N hydrochloric acid and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC(RP18 column; acetonitrile/water gradient). Yield: 133 mg (57% of theory)LC-MS (Method 5B): Rt=2.17 min; MS (ESIpos): m/z=454 [M+H]+;1H-NMR (400 MHz, DMSO-d6): δ=7.80 (d, 1H), 7.70 (d, 2H), 7.52 (d, 2H), 3.74 (d, 2H), 3.63 (d, 1H), 3.56 (br. s., 4H), 3.17 (br. s., 4H), 2.97 (br. s., 1H), 2.84-2.73 (m, 1H), 2.02 (d, 1H), 1.78-1.66 (m, 2H), 1.54-1.66 (m, 5H), 1.48 (br. s., 2H).

Reference： [1]Current Patent Assignee: BAYER AG - US2012/46268, 2012, A1 Location in patent: Page/Page column 84

55
[ 4524-93-0 ]
cis-1-({3-amino-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)piperidine-4-carbonitrile hydrochloride [ No CAS ]
cis-N-{1-[(4-cyanopiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In dichloromethane at 0 - 20℃; for 16h;	178 At 0° C., 90 mg (0.21 mmol) of the compound from Example 69A were initially charged in 5.0 ml of dichloromethane, and 86 μl (62 mg, 1.5 eq.) of triethylamine, 37 μl (41 mg, 0.31 mmol) of cyclopentanecarbonyl chloride and 7.5 mg (0.062 mmol) of 4-(dimethylamino)pyridine were added. The reaction mixture was allowed to warm to RT and was stirred at RT for a further 16 h.The mixture was washed with 1N hydrochloric acid and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (RP18 column; acetonitrile/water gradient). Yield: 74.8 mg (77% of theory). The enantiomer separation of 74.8 mg of the racemate according to Method 17D gave 27 mg of the compound from Example 178 (enantiomer 1) and 28 mg of the compound from Example 179 (enantiomer 2).HPLC (Method 8E): Rt=5.96 min, >99.0% ee;LC-MS (Method 11B): Rt=1.11 min; MS (ESIpos): m/z=477 [M+H]+;1H-NMR (400 MHz, DMSO-d6): δ=7.80 (d, 1H), 7.70 (d, 2H), 7.52 (d, 2H), 3.80-3.65 (m, 2H), 3.60 (d, 1H), 3.14-2.90 (m, 4H), 2.85-2.72 (m, 1H), 2.01 (d, 1H), 1.85 (br. s, 2H), 1.77-1.39 (m, 16H), 4H obscured.

Reference： [1]Current Patent Assignee: BAYER AG - US2012/46268, 2012, A1 Location in patent: Page/Page column 87

56
[ 4524-93-0 ]
[ 294190-18-4 ]
[ 1403595-77-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine; at 20℃; for 2h;	[01276] Step 4: Synthesis of methyl -chloro-3-(cyclopentanecarboxamido)-2-methylbenzoate[01277] To a stirred solution of <strong>[294190-18-4]methyl 3-amino-5-chloro-2-methylbenzoate</strong> (0.4 g, 2.0 mmol) in pyridine (2 mL), cyclopentyl chloride (0.39 mL, 3.00 mmol) was added at 0 C. The reaction mixture was stirred at room temperature for 2h. After complete consumption of the starting material the reaction was quenched with ice water. The resulting precipitate was filtered of to provide desired product (0.5 g, 84%).

Reference： [1]Patent: WO2012/142513,2012,A1 .Location in patent: Page/Page column 322-323

57
[ 4524-93-0 ]
[ 117642-16-7 ]
[ 353789-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 20℃;

Reference： [1]Thur, Yithachu; Bhalerao, Amit; Munshi, Zaki; Pansare, Nisha; Mann, Klaus; Hanauer, Guido; Kley, Hans-Peter; Nappe, Sandra; Weiss-Haljiti, Cornelia; Ostermann, Claude; Zitt, Christof; Schaefer, Michaela; Mondal, Dibyendu; Ali Siddiki, Afsar; Armugam, Velavan; Gudaghe, Vinod; Gupta, Mahendra; Rayudu, Pramila; Dautzenberg, Frank M.; Das Sarma, Koushik [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7314 - 7321]

58
[ 4524-93-0 ]
[ 2010-06-2 ]
[ 362482-22-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dmap In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;
63%	With triethylamine In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere;	44 General procedure for the synthesis of compounds 4b-4f, 4h, 4i, 5h, 6a-6c, 7a-7c, 8a, 8b, 9b-9h, 10a-10f, 11a, 11b, 12a-12d, 13a-13f, 14a, 14c, and 15a-15h General procedure: To a mixture of compounds 3a-3p (1equiv) and acid chloride (1equiv) in THF (∼20mL), triethylamine (3equiv) was added. The mixture was stirred at room temperature for 15min followed by filtration. The solvents were evaporated and the residue was purified by column chromatography.

Reference： [1]Zheng, Shilong; Zhong, Qiu; Jiang, Quan; Mottamal, Madhusoodanan; Zhang, Qiang; Zhu, Naijue; Burow, Matthew E.; Worthylake, Rebecca A.; Wang, Guangdi [ACS Medicinal Chemistry Letters, 2013, vol. 4, # 2, p. 191 - 196]
[2]Khalil, Ahmed; Edwards, Jessica A.; Rappleye, Chad A.; Tjarks, Werner [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 3, p. 532 - 547]

59
[ 4524-93-0 ]
[ 5234-86-6 ]
[ 1463497-68-8 ]

Yield	Reaction Conditions	Operation in experiment
32%	In dichloromethane; at 0 - 20℃;Inert atmosphere;	General procedure: To a stirred solution of compound 16 (500 mg, 2.7 mmol) in DCM (50 mL), cyclohexanecarbonyl chloride (532 L, 4.0 mmol) was added at 0 C. The mixture was stirred at room temperature overnight. The reaction was quenched with NaHCO3 (aq.), extracted with DCM (50 mL × 3). The organic phases were then processed in the usual way and chromatographed (1:1 petroleum ether/ EtOAc) to afforded compound 19 (350 mg, 43%) as white solid.

Reference： [1]Molecules,2013,vol. 18,p. 9163 - 9178

60
[ 4524-93-0 ]
[ 1444335-07-2 ]
[ 1616249-54-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine In dichloromethane at 20℃;	1.1. General procedure for the synthesis of the benzyl-protected amidopyridinols 10 and the amidopyridinols 5. General procedure: To a solution of 9 (1.0 equiv.) in CH2Cl2 (6 mL per 1.0 mmol of 9) was added Et3N (1.4equiv.), acid chloride (1.2 equiv.), and the resulting mixture was stirred at room temperature until the starting material 9 disappeared on TLC. The mixture was diluted with CH2Cl2 and the aqueous layer was extracted with CH2Cl2. The combined organic solution was washed with saturated sodium bicarbonate, water, and brine. The organic solution was then dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by silicagel column chromatography to give 10.
93%	With triethylamine In dichloromethane at 20℃; for 4h;	7-7 Preparation of N-(5-benzyloxy-3,4,6-trimethylpyridine-2-yl)cyclopentane carboxamide (7g) Example 7-7 Preparation of N-(5-benzyloxy-3,4,6-trimethylpyridine-2-yl)cyclopentane carboxamide (7g) 0.091 mL (0.654 mmol) of triethylamine and 0.069 mL (0.560 mmol) of cyclopentane carbonyl chloride were sequentially added to 10 mL of CH2Cl2 containing 113 mg (0.467 mmol) of Compound 6, and then, the mixed solution was stirred at room temperature for 4. The reaction solution was diluted with 100 mL of CH2Cl2, and then, washed with 10 mL of saturated sodium hydrogencarbonate aqueous solution twice and 10 mL of water twice. The CH2Cl2 solution was washed with saturated brine, dried with anhydrous MgSO4, filtered, and then, concentrated under reduced pressure. The residues were purified by column chromatography (EtOAC:Hex=1:3), thereby obtaining 148 mg (93%) of yellow solids, i.e., Compound 7g. 1H-NMR (250 MHz, CHCl3-d) δ 8.71 (br s, 1H), 7.34-7.45 (m, 5H), 4.74 (s, 2H), 2.73-2.85 (m, 1H), 2.40 (s, 3H), 2.23 (s, 3H), 2.09 (s, 3H), 1.55-1.90 (m, 8H) ppm
93%	With triethylamine In dichloromethane at 20℃; for 4h;	7-7 Preparation of N-(5-benzyloxy-3,4,6-trimethylpyridine-2-yl)cyclopentane carboxamide (7g) 0.091 mL (0.654 mmol) of triethylamine and 0.069 mL (0.560 mmol) of cyclopentane carbonyl chloride were sequentially added to 10 mL of CH2Cl2 containing 113 mg (0.467 mmol) of Compound 6, and then, the mixed solution was stirred at room temperature for 4. The reaction solution was diluted with 100 mL of CH2Cl2, and then, washed with 10 mL of saturated sodium hydrogencarbonate aqueous solution twice and 10 mL of water twice. The CH2Cl2 solution was washed with saturated brine, dried with anhydrous MgSO4, filtered, and then, concentrated under reduced pressure. The residues were purified by column chromatography (EtOAC:Hex=1:3), thereby obtaining 148 mg (93%) of yellow solids, i.e., Compound 7g.

93%

With triethylamine In dichloromethane at 20℃;

General procedure for N-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)amides (2) General procedure: Amide formation: To a solution of 8 (1.0 equiv.) in CH2Cl2 (6 mL per 1.0 mmol of 8) was addedEt3N (1.4 equiv.), acid chloride (1.2 equiv.), and the mixture was stirred at room temperature.The mixture was diluted with CH2Cl2 and the aqueous layer was extracted with CH2Cl2. Thecombined organic solution was washed with saturated sodium bicarbonate, water, and brine.The organic solution was then dried over MgSO4, filtered and the filtrate was concentrated invacuo. The residue was purified by silica gel column chromatography to give 9. Debenzylationmethod1: To a solution of 9 in methanol (10 mL per 1.0 mmol of 9) was added palladium (10%on activated carbon, 20 mg per 100 mg of 9). The mixture was stirred with hydrogen balloonat room temperature. The solid in the reaction mixture was filtered through a Celite pad andthe filtrate was filtered again with a syringe membrane filter. The filtrate was concentrated togive 2. Debenzylation-method 2: To a cooled solution of 9 in CH2Cl2 (10 mL per 1.0 mmol of9) was added pentamethylbenzene (3 equiv.) and 1.0 M BCl3 (2 equiv.) at an ice-bath. Themixture was stirred at iced bath. The reaction mixture was quenched with a solution of 10%methanol in chloroform (1 mL) and stirred for additional 1 h at room temperature. The reactionsolution was concentrated and the residue was purified by silica gel column chromatographyto give 2.

Reference： [1]Lee, Hyunji; Banskota, Suhrid; Kim, Dong-Guk; Been, Jae-Hui; Jin, You-Jin; Gautam, Jaya; Jang, Hyeonjin; Nam, Tae-Gyu; Kim, Jung-Ae; Jeong, Byeong-Seon [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 14, p. 3131 - 3136]
[2]Current Patent Assignee: YEUNGNAM UNIVERSITY - US2016/68489, 2016, A1 Location in patent: Paragraph 0104; 0105
[3]Current Patent Assignee: YEUNGNAM UNIVERSITY - KR101612179, 2016, B1 Location in patent: Paragraph 0036; 0096; 0097
[4]Karmacharya, Ujjwala; Regmi, Sushil Chandra; Awasthi, Bhuwan Prasad; Chaudhary, Prakash; Kim, Ye Eun; Lee, Iyn-Hyang; Nam, Tae-gyu; Kim, Jung-Ae; Jeong, Byeong-Seon [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 43]

61
[ 4524-93-0 ]
[ 481-39-0 ]
5,8-dioxo-5,8-dihydronaphthalen-1-yl cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With dmap In pyridine; dichloromethane for 0.75h; Inert atmosphere;	3 5,8-Dioxo-5,8-dihydronaphthalen-1-ylcyclopentanecarboxylate (8) Similar to previously reported procedure, cyclopentoyl chloride(3 equiv, 29 μL) was added to a solution of 7 (0.08 mmol,14 mg) and DMAP (0.2 equiv, 2 mg) in 200 μL pyridine/200 μL DCM. After stirring for 45 min, the reaction was diluted with 1N HCl and extracted with DCM. Purification by pTLC with 30% EtOAc in hexane afforded 8 as a yellow solid (12 mg, 55%). 1H NMR (600 MHz, CDCl3) d 8.04 (dd, J = 7.7, 1.3 Hz, 1H), 7.75 (t,J = 7.9 Hz, 1H), 7.37 (dd, J = 8.1, 1.3 Hz, 1H), 6.93 (d, J = 10.3 Hz, 1H),6.84 (d, J = 10.3 Hz, 1H), 3.22-3.09 (m, 1H), 2.19-2.05 (m, 4H),1.90-1.76 (m, 2H), 1.76-1.63 (m, 2H).13C NMR (151 MHz, CDCl3) d 184.44, 183.78, 174.96, 149.94,140.11, 137.37, 134.83, 133.68, 130.00, 125.00, 123.74, 44.12,30.00, 26.01.ESI-TOF-MS (m/z): [M+H]+ calcd 271.0965, obsd 271.0965.

Reference： [1]Bremer, Paul T.; Hixon, Mark S.; Janda, Kim D. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 3971 - 3981]

62
[ 4524-93-0 ]
[ 39136-63-5 ]
N-(5-phenylthiazol-2-yl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; In tetrahydrofuran; at 20℃; for 0.25h;Inert atmosphere;	General procedure: To a mixture of compounds 3a-3p (1equiv) and acid chloride (1equiv) in THF (?20mL), triethylamine (3equiv) was added. The mixture was stirred at room temperature for 15min followed by filtration. The solvents were evaporated and the residue was purified by column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 532 - 547

63
[ 4524-93-0 ]
[ 1446-61-3 ]
C₂₆H₃₉NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine; In dichloromethane; at 0 - 23℃;	To a solution of <strong>[1446-61-3](+)-dehydroabietylamine</strong>(1.0mmol) and triethylamine (3.0 mmol) in CH2Cl2 (5 mL), a solution of the corresponding acyl chloride (1.10 mmol) in CH2Cl2 (5 mL) was slowly added dropwise via syringe at 0 C. Theresulting reaction mixture was allowed to be warmed and was stirred at 23 C for 1-12 hr based on the reaction?s progress (TLC, MS) before it was quenche dwith an aqueous NH4Cl solution (10 mL). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (5mL x 3). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure. The resulting crude product was purified via flash columnchromatography (SiO2; isocratic eluent: 20% EtOAc in petroleum ether) to provide the amide product.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 102,p. 9 - 13

64
[ 4524-93-0 ]
[ 2418-95-3 ]
[ 75691-94-0 ]

Yield	Reaction Conditions	Operation in experiment
76.26%	With sodium carbonate; sodium hydroxide; In water; ethyl acetate; at 0 - 10℃; for 3h;Inert atmosphere;	[0239] To a mixture of compound 1.5 (10.00 g, 40.60 mmol, 1.00 eq) and (0621) cyclopentanecarbonyl chloride (5.92 g, 44.66 mmol, 5.43 mL, 1.10 eq) in EtOAc (20.00 mL) was added Na2C03 (5.16 g, 48.72 mmol, 1.20 eq) and NaOH (1.64 g, 41.01 mmol, 1.01 eq) in 30 (80.00 mL) at 0C under N?. The mixture was stirred at 10C for 3 hours. EtOAc was removed and then the solution was cooled to 0 C, and the pH was adjusted to 6-7 with HCl (IN). The suspension was filtered, and the filter cake was washed with 50 mL of PE and dried under vacuum to afford compound 1.4 (10.60 g, 30.96 mmol, 76.26% yield) as a white solid. LCMS (ESI): m/z: [M + H] calcd for C 7H30 2O5: 343.4: found 343.2; RT=1.022 min.
		(2S)-6-(tert-butoxycarbonylamino)-2-(cyclopentanecarbonylamino)hexanoic acid (43d) To a solution of <strong>[2418-95-3](2S)-2-amino-6-(tert-butoxycarbonylamino)hexanoic acid</strong> (5.00 g, 20.30 mmol, 1.00 eq) in H2O (40 mL) were added NaOH (820 mg, 20.50 mmol, 1.01 eq) and Na2CO3 (2.58 g, 24.36 mmol, 1.20 eq). After being stirred for 10 min, it was cooled to 0 C. and cyclopentanecarbonyl chloride (2.96 g, 22.33 mmol, 1.10 eq) in EA (20 mL) was added under 0 C. The reaction mixture was stirred at 10 C. for 14 h. EA was removed and then solution was cooled to 0 C., the pH was adjusted to 6-7 with solid KHSO4. The suspension was filtered and the filter cake was washed with PE (60 mL) and dried in vacuo to give (2S)-6-(tert-butoxycarbonylamino)-2-(cyclopentanecarbonylamino)hexanoic acid (4.50 g, crude) as a white solid.

Reference： [1]Patent: WO2018/53353,2018,A1 .Location in patent: Paragraph 0239
[2]Patent: US2016/96830,2016,A1 .Location in patent: Paragraph 0470-0471

65
[ 18514-84-6 ]
[ 4524-93-0 ]
C₁₄H₁₆N₂O₂ [ No CAS ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 628 - 639

66
[ 4524-93-0 ]
[ 181954-34-7 ]
(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(cyclopentanecarboxamido)propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With sodium hydroxide; In tetrahydrofuran; at 0 - 20℃; for 1h;	S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(cyclobutanecarboxamido)propanoic acid Cyclobutanecarbonyl chloride (72.7 mg, 0.613 mmol) and NaOH (0.735 mL, 0.735 mmol) were dropped at the same time to a stirred solution of <strong>[181954-34-7](S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-aminopropanoic acid</strong> (200 mg, 0.613 mmol) in THF (1.5 mL) and NaOH (1N, 0.8 mL) at 0 C. The reaction mixture was allowed to stir at rt for 1 h at which time LC-MS showed the desired product peak. The reaction solution was acidified with 1N HCl and extracted with EtOAc (60 mL*1). The crude was purified via flash chromatography (ISCO, silica gel, 12 g column; flow rate 30 mL/min, 100% DCM to 20% MeOH/DCM). Fractions containing the desired product were combined and dried via centrifugal evaporation to provide the title compound (156 mg, 61%). Analysis LCMS Condition A: Retention time=0.99 min; ESI-MS(+) m/z 423.1 (M+H) 1H NMR (400 MHz, methanol-d4) delta 7.80 (d, J=7.5 Hz, 2H), 7.67 (t, J=6.4 Hz, 2H), 7.44-7.37 (m, 2H), 7.35-7.27 (m, 2H), 4.38-4.31 (m, 2H), 4.27-4.19 (m, 1H), 3.69-3.47 (m, 2H), 2.61 (s, 1H), 1.88-1.53 (m, 9H)

Reference： [1]Patent: US9308236,2016,B2 .Location in patent: Page/Page column 294; 295

67
[ 4524-93-0 ]
[ 161420-87-7 ]
(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(cyclopentanecarboxamido)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium hydroxide; In tetrahydrofuran; at 0 - 20℃; for 1h;	(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(cyclopentanecarboxamido)butanoic acid Cyclopentanecarbonyl chloride (78 mg, 0.588 mmol) and NaOH (0.705 mL, 0.705 mmol) were dropped at the same time to a stirred solution of <strong>[161420-87-7](S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-aminobutanoic acid</strong> (200 mg, 0.588 mmol) in THF (1.5 mL) and of NaOH (1N, 0.7 mL) at 0 C. The reaction mixture was allowed to stir at rt for 1 h at which time LC-MS showed desired product peak. The reaction solution was acidified with 1N HCl and extracted with EtOAc (60 mL*1). The crude materials were purified via flash chromatography (ISCO, silica gel, 12 g column; flow rate 30 mL/min, 100% DCM to 20% MeOH/DCM). Fractions containing the desired product were combined and dried via centrifugal evaporation to provide the title compound (84.1 mg, 33%). Analysis LCMS Condition A: Retention time=0.98 min; ESI-MS(+) m/z 437.1 (M+H) 1H NMR (400 MHz, methanol-d4) delta 7.79 (d, J=7.5 Hz, 2H), 7.72-7.64 (m, 2H), 7.42-7.35 (m, 2H), 7.34-7.26 (m, 2H), 4.41-4.30 (m, 2H), 4.26-4.14 (m, 2H), 3.24-3.13 (m, 1H), 2.59 (t, J=7.8 Hz, 1H), 2.05 (s, 1H), 1.91-1.62 (m, 8H), 1.64-1.50 (m, 2H)

Reference： [1]Patent: US9308236,2016,B2 .Location in patent: Page/Page column 296

68
[ 4524-93-0 ]
[ 921599-74-8 ]
(S)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: benzyl (2S)-2-methyl-4-oxopiperidine-1-carboxylate With 5%-palladium/activated carbon; hydrogen In ethanol for 1h; Stage #2: Cyclopentanecarboxylic acid chloride With triethylamine In dichloromethane at 20℃; for 1h;	20.1 Steps 1 : (S)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-one Steps 1 : (S)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-one. A flask with a mixture of benzyl (S)-2-methyl-4-oxopiperidine-1-carboxylate (500 mg, 2.02 mmol) and Pd/C (5% by weight, 215 mg) in EtOH (10 mL) was evacuated with water aspiration and then put under hydrogen gas. The mixture was stirred under 1.1 bar hydrogen over-pressure for 1 h. The mixture was filtered through a Celite plug, and the filtrate was concentrated in vacuo. To the residue was added DCM (10 ml) followed by triethylamine (1.41 mL, 10.1 mmol) and then cyclopentanecarbonyl chloride (492 μ, 4.04 mmol) dropwise. The reaction mixture was stirred at room temperature for 1 h, whereupon the reaction was quenched with 40 ml water followed by extraction in a phase separator (4 x DCM). The combined organic extracts were evaporated and the residue was purified by flash chromatography (EtOAc/heptane; 1 : 1) to provide the title compound (301 mg, 71 %) as a colorless oil. 1 H NMR (500 MHz, CDCI3): δ 5.24-4.84 (2 br s, 1 H), 4.64-4.10 (2 br s, 1 H), 3.55-3.1 1 (2 br s, 1 H), 2.95 (m, 1 H), 2.65 (dd, J=6.7, 14.4Hz, 1 H), 2.50-2.30 (m, 3H), 1.93-1.77 (m, 6H), 1.64-1.56 (m, 2H), 1.29-1.16 (m, 3H)

Reference： [1]Current Patent Assignee: PFIZER INC - WO2016/120850, 2016, A1 Location in patent: Page/Page column 59-60

69
[ 4524-93-0 ]
[ 446065-11-8 ]
[ 17773-63-6 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 1856 - 1863

70
[ 4524-93-0 ]
[ 141-78-6 ]
[ 24922-00-7 ]

Yield	Reaction Conditions	Operation in experiment
		1b) 1 -(3-Bromo-phenyl)-5-cyclopentyl-1 H-pyrazole-4-carboxylic acid ethyl ester A stirred solution of diispropylamine (8.23 g, 81 .4 mmol) in dry THF (10 ml_) under N2 at 0C was treated with nBuLi (2.5M in hexane, 31 .5 ml_, 78.7 mmol). After 30 minutes the solution was cooled to -78C. Dry EtOAc (7.69 ml_, 78.7 mmol) was then added dropwise. After 5 min, a solution of cyclopentane carbonyl chloride (3.48 g, 26.2 mmol) in dry THF (2 ml_) was added in one go. After 5 min, the cool bath was removed and the mixture was allowed to warm to room temperature. The mixture was diluted with 1 N HCI (30 ml_) and then extracted with Et20 (2 x 30 ml_). The combined organic phase was dried (MgS04), filtered, and concentrated 7.8 g of crude 3-cyclopentyl-3-oxo-propionic acid ethyl ester. A mixture of this material (2.4 g, 13.0 mmol) and DMF-dimethyl acetal was stirred in a microwave reactor at 130C for 15min. After cooling, the stirred mixture was diluted with EtOH (10 ml_) and treated with 3-bromophenylhydrazine HCI (2.91 g, 13.0 mmol) followed by triethylamine (2.61 g, 26.1 mmol). After 16 h at room temperature the mixture was partitioned between EtOAc and water and then the organic phase washed with water, 0.5 N HCI, water and then brine before it was dried (MgS04), filtered, and concentrated to give the crude product (4.5 g, 12.4 mmol). LC-MS m/z 363 (M + H) +, 1 .61 (ret. time), basic method.

Reference： [1]Patent: WO2017/60854,2017,A1 .Location in patent: Page/Page column 156; 157

71
[ 4524-93-0 ]
[ 74-89-5 ]
[ 4492-50-6 ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 12307 - 12311
Angew. Chem.,2017,vol. 129,p. 12475 - 12479,5

72
[ 4524-93-0 ]
[ 58436-28-5 ]
5-(4-((cyclopentanecarbonyl)oxy)phenethyl)-1,3-phenylene dicyclopentanecarboxylate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 143,p. 1254 - 1260

73
[ 4524-93-0 ]
[ 39657-45-9 ]
cyclopentyl-(2-isoxazolidinyl)methanone [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 16342 - 16346
Angew. Chem.,2017,vol. 129,p. 16560 - 16564,5

74
[ 4524-93-0 ]
[ 138402-05-8 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 499 - 501

75
[ 1131-61-9 ]
[ 4524-93-0 ]
[ 939-23-1 ]
2-cyclopentyl-4-phenylpyridine [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 3487 - 3490

76
[ 4524-93-0 ]
[ 141973-33-3 ]
N(2-((5-methoxy-2-nitrophenyl)amino)ethyl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine In dichloromethane at 20℃; for 2h;	6.A (A) N (2- ( (5methoxy2-nitrophenyl) amino) ethyl) cyclopentane carboxamide N1 (5methoxy2nitrophenyl) ethanel, 2diamine (Ig, 4 . 7 Smmol ) , dl. ch i.oromethan.e (5 Omi. ) and triethvi.a.mine0 67ml, 4 . 8 Ommol. ) were aoded to a 1 OOmi. reactor with magnetic stirring. The reaction medium was kept under stirring and a solution of cyclopentanecarbonyl chloride (0.585ml, 4,73rnmoi) in dichloromethane (lOml) was slowly added through an addition funnel. The reaction medium was kept under stirring at room temperature for 2 hours. After the completion of the reaction, 10% aqueous hydrochloric acid solution (lOml) was added. The dichloromethane was separated and the aqueous phase extracted withdichloromethane (2x2Oml) The organic phase was washed with 5% aqueous bicarbonate solution (lOUmi) and saturated sodium chloride solution (lOOml) The organic extract was separated, dried with anhydrous magnesium sulfate and roto evaporated, yielding a yellow solid product wh.ich was used directly in the next stepS (m=L2g. Yield: 83%)
	In ethanol at 80℃; for 1h;

Reference： [1]Current Patent Assignee: ACHE LABORATORIOS FARMACEUTICOS SA - WO2018/76090, 2018, A1 Location in patent: Page/Page column 51; 52
[2]Ferreira, Marcos Antonio; Azevedo, Hatylas; Mascarello, Alessandra; Segretti, Natanael Dante; Russo, Elisa; Russo, Valter; Guimarães, Cristiano Ruch Werneck [Journal of Medicinal Chemistry, 2021, vol. 64, # 4, p. 1904 - 1929]

77
[ 4524-93-0 ]
[ 5473-01-8 ]
N-(2-bromo-6-methoxyphenyl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃;	To a 500 mL round-bottom flask was added <strong>[5473-01-8]2-bromo-6-methoxyaniline</strong> (commercially available from Apollo Scientific Ltd., Manchester, UK, 8.60 g, 42.6 mmol) and N,N-diisopropylethylamine (14.81 mL, 85 mmol) in DCM (142 mL). At 0 °C cyclopentanecarbonyl chloride (5.69 mL, 46.8 mmol) in DCM (50 mL) was added dropwise via syringe. The reaction mixture was stirred at 0 °C -RT. The reaction mixture was diluted with 1.0 N HC1 and extracted with DCM. The organic extract was washed with a saturated NaC1 solution and dried over Na2504. The solution was filtered and concentrated in vacuo to the title compound (12 g, 40.2 mmol, 95 percent yield) as a whitesolid, which was of >85percent purity by 1H NMR and LCMS. The material was directly used in the next step without purification. LCMS-ESI (pos.), m/z: 298.0 (M+H).

Reference： [1]Patent: WO2018/93577,2018,A1 .Location in patent: Paragraph 0255

78
[ 4524-93-0 ]
[ 593-51-1 ]
[ 4492-50-6 ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 8781 - 8787

79
[ 4524-93-0 ]
[ 41058-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / N,N-dimethyl-formamide / 1 h / 20 °C 2: calcium oxide; quinoline / 1.25 h / 217 - 310 °C

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2018/109650, 2018, A1

80
[ 4524-93-0 ]
[ 375853-82-0 ]
cyclopentyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
107.98 g	With triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Schnute, Mark E.; Wennerstal, Mattias; Alley, Jennifer; Bengtsson, Martin; Blinn, James R.; Bolten, Charles W.; Braden, Timothy; Bonn, Tomas; Carlsson, Bo; Caspers, Nicole; Chen, Ming; Choi, Chulho; Collis, Leon P.; Crouse, Kimberly; Färnegardh, Mathias; Fennell, Kimberly F.; Fish, Susan; Flick, Andrew C.; Goos-Nilsson, Annika; Gullberg, Hjalmar; Harris, Peter K.; Heasley, Steven E.; Hegen, Martin; Hromockyj, Alexander E.; Hu, Xiao; Husman, Bolette; Janosik, Tomasz; Jones, Peter; Kaila, Neelu; Kallin, Elisabet; Kauppi, Björn; Kiefer, James R.; Knafels, John; Koehler, Konrad; Kruger, Lars; Kurumbail, Ravi G.; Kyne, Robert E.; Li, Wei; Löfstedt, Joakim; Long, Scott A.; Menard, Carol A.; Mente, Scot; Messing, Dean; Meyers, Marvin J.; Napierata, Lee; Nöteberg, Daniel; Nuhant, Philippe; Pelc, Matthew J.; Prinsen, Michael J.; Rhönnstad, Patrik; Backström-Rydin, Eva; Sandberg, Johnny; Sandström, Maria; Shah, Falgun; Sjöberg, Maria; Sundell, Aron; Taylor, Alexandria P.; Thorarensen, Atli; Trujillo, John I.; Trzupek, John D.; Unwalla, Ray; Vajdos, Felix F.; Weinberg, Robin A.; Wood, David C.; Xing, Li; Zamaratski, Edouard; Zapf, Christoph W.; Zhao, Yajuan; Wilhelmsson, Anna; Berstein, Gabriel [Journal of Medicinal Chemistry, 2018, vol. 61, # 23, p. 10415 - 10439]

81
[ 4524-93-0 ]
[ 4414-89-5 ]
1-(cyclopentanecarbonyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine; In dichloromethane; at 0 - 20℃; for 4h;	General procedure: To a cooled (0 C) suspension of 1a-h20-26 (0.56 mmol) in anhydrousCH2Cl2 (2 mL), 0.72 mmol Et3N and 1.67 mmol of the appropriatechloride were added. The mixture was stirred at 0 C for 2 h and then atroom temperature for an additional 2 h. The solvent was evaporated,cold water was added, and the mixture was neutralized with 0.5 NNaOH. The reaction mixture was extracted with CH2Cl2 (3×15 mL),the solvent was dried over sodium sulfate, evaporated in vacuo, and thefinal compounds were purified by crystallization from ethanol (2a-i,3a,b,e, and 4b) or by column chromatography using cyclohexane/ethylacetate in different ratios: 1:1 (3d), 2:1 (3c and 4a), 3:1 (2l, 4b, 5a and5e), 5:1 (5c), or 6:1 (5b and 5d) as eluents

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5583 - 5595

82
[ 74370-93-7 ]
[ 4524-93-0 ]
N-(4-tert-butyl-1,3-thiazol-2-yl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; at 20℃; for 1h;	To a solution of 4-(iert-butyl)thiazol-2-amine (200 mg, 1.28 mmol), and DIEA (438 muIota_, 2.56 mmol) in THF (1.5 mL) was added cyclopentanecarbonyl chloride (172 muL, 1.41 mmol). After allowing to stand at ambient temperature for 1 h, the mixture was washed with 1 N NaOH (2X2 mL), brine (2X2 mL), dried with sodium sulfate, filtered, and concentrated. Flash chromatography (0-20% hexanes/ethyl acetate) provided N-(4-tert-butyl-1 ,3-thiazol-2- yl)cyclopentanecarboxamide (286 mg, 89% yield) (A127) as a colorless solid. LCMS for C13H2oN2OS, found 253 [M+H]+.

Reference： [1]Patent: WO2019/46668,2019,A1 .Location in patent: Paragraph 00136

83
[ 4524-93-0 ]
[ 81-54-9 ]
2-O-cyclopentanecarbonyloxy-1,4-dihydroxy-9,10-anthraquinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With pyridine; at 30 - 65℃;	General procedure: A weighed portion of 1 (2.56 g, 0.01 mol) was dissolved in Py (50 mL), treated with the appropriate carboxylic acid chloride (2-5, 0.01-0.03 mol), stirred vigorously, and heated (30-65C). The course of the reaction and purity of isolated derivatives were monitored using TLC. When the reaction was finished (3-10 h), a part of the solvent was removed. The resulting concentrated solution was worked up with H2O and acidified by HCl to pH 4. The resulting precipitate was filtered off and dried. The products were isolated by column chromatography over silica gel with elution by hexane with a gradual switch to hexane-EtOAc mixtures (gradient from 100:1 to 1:5). Recrystallization used hexane-EtOAc (1:5).

Reference： [1]Chemistry of Natural Compounds,2019,vol. 55,p. 622 - 625
Khim. Prir. Soedin.,2019,p. 536 - 538,3

84
[ 4524-93-0 ]
[ 66217-55-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: pyridine / diethyl ether / 1 h / -15 °C 2.1: N,N-dimethyl-formamide / 0.33 h / 25 °C / Inert atmosphere 2.2: 1 h / 25 °C / Inert atmosphere

Reference： [1]Wei, Dian; Liu, Tu-Ming; Zhou, Bo; Han, Bing [Organic Letters, 2020, vol. 22, # 1, p. 234 - 238]

85
[ 4524-93-0 ]
[ 142-81-4 ]
N-hexyl-N-(trifluoromethyl)cyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate / ethyl acetate; water 2: silver trifluoromethanesulfonate; 2-fluoropyridine; Selectfluor; cesium fluoride / chlorobenzene; dichloromethane / 24 h / 20 °C / Schlenk technique; Inert atmosphere; Glovebox

Reference： [1]Zhang, Zhenzhen; He, Jiayan; Zhu, Lin; Xiao, Haiwen; Fang, Yewen; Li, Chaozhong [Chinese Journal of Chemistry, 2020, vol. 38, # 9, p. 924 - 928]

86
[ 4524-93-0 ]
[ 142-81-4 ]
N-hexylcyclopentanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In water; ethyl acetate

Reference： [1]Zhang, Zhenzhen; He, Jiayan; Zhu, Lin; Xiao, Haiwen; Fang, Yewen; Li, Chaozhong [Chinese Journal of Chemistry, 2020, vol. 38, # 9, p. 924 - 928]

87
[ 4524-93-0 ]
tert-butyl 4-((4-(4-chlorophenoxy)phenyl)glycyl)piperidine-1-carboxylate [ No CAS ]
tert-butyl 4-(N-(4-(4-chlorophenoxy)phenyl)-N-(cyclopentanecarbonyl)glycyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: tert-butyl 4-((4-(4-chlorophenoxy)phenyl)glycyl)piperidine-1-carboxylate With triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: Cyclopentanecarboxylic acid chloride In dichloromethane at 20℃; for 0.5h;	General synthesis of intermediate m31-m38 General procedure: To a solution of m2 (2.0 g, 4.49 mmol) in 30 mL anhydrous DCM was added TEA (0.91 g, 8.99 mmol) at 0 . The mixture was stirred for 0.5 h before the addition of different substituted acylchlorides (4.94 mmol). After the mixture was stirred for 0.5 h at room temperature, the solvent was extracted with water and DCM, the combined organic layer was washed with brine, dried over with anhydrous Na2SO4, and concentrated in vacuo. Purified of the residue via flash column chromatography on silica gel afforded m31-m38.
62%	Stage #1: tert-butyl 4-((4-(4-chlorophenoxy)phenyl)glycyl)piperidine-1-carboxylate With triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: Cyclopentanecarboxylic acid chloride In dichloromethane at 20℃; for 0.5h;	General synthesis of intermediate m31-m38 General procedure: To a solution of m2 (2.0 g, 4.49 mmol) in 30 mL anhydrous DCM was added TEA (0.91 g, 8.99 mmol) at 0 . The mixture was stirred for 0.5 h before the addition of different substituted acylchlorides (4.94 mmol). After the mixture was stirred for 0.5 h at room temperature, the solvent was extracted with water and DCM, the combined organic layer was washed with brine, dried over with anhydrous Na2SO4, and concentrated in vacuo. Purified of the residue via flash column chromatography on silica gel afforded m31-m38.

Reference： [1]Huang, Junyang; Huang, Yunyuan; Li, Jian; Li, Wangsheng; Li, Xiaokang; Sun, Annan; Wang, Lan; Wang, Wei; Xu, Yixiang; Zhang, Chao; Zhang, Haiyan; Zhu, Jin [European Journal of Medicinal Chemistry, 2022, vol. 236]
[2]Huang, Junyang; Huang, Yunyuan; Li, Jian; Li, Wangsheng; Li, Xiaokang; Sun, Annan; Wang, Lan; Wang, Wei; Xu, Yixiang; Zhang, Chao; Zhang, Haiyan; Zhu, Jin [European Journal of Medicinal Chemistry, 2022, vol. 236]

88
[ 4524-93-0 ]
C₁₄H₁₁Br₃O₃ [ No CAS ]
C₂₀H₁₉Br₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	4.1.7. General procedure for the synthesis of compounds 13a-13 L General procedure: The synthetic route of compound 13: take propionyl chloride as anexample, dissolve compound 12 (50 mg, 0.1 mmol) in anhydrousdichloromethane (6 ml), add triethylamine 3 ml of propionyl chlorideslowly at 0 C, then slowly add propionyl chloride (15 mg, 0.16 mmol) toroom temperature, react under the protection of inert gas for 2 h, quenchit with saturated sodium bicarbonate solution at the end of the reaction,extract with ethyl acetate and combine with organic phase anhydrousmagnesium sulfate to dry. The compound 13a was concentrated andseparated by silica gel column chromatography (PE: DCM = 5:1).Compound 13a: White solid, yield 70%; 1H NMR (400 MHz, CDCl3):δH 7.40 (d, J = 2.2 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.16 (dd, J = 8.1,1.8 Hz, 1H), 7.08 (d, J = 2.2 Hz, 1H), 6.51 (d, J = 1.8 Hz, 1H), 5.30 (s,2H), 3.76 (s, 3H), 2.82 (t, J = 8.0 Hz, 1H), 1.77-1.95 (m, 6H), 1.71 (td, J= 6.6, 3.7 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3): δC 176.58 (C),155.40 (C), 153.76 (C), 139.94 (C), 130.71 (CH), 127.43 (CH), 125.44(CH), 124.02 (C), 122.26 (C), 119.18 (C), 118.84 (C), 116.08 (CH),115.60 (CH), 61.01 (CH2), 56.50 (CH3), 43.90 (CH), 30.06 × 2 (CH2),25.86 × 2 (CH2) ppm. HR-ESI-MS: [M + Na]+ calcd. for C20H19Br3NaO4582.8726, found: 582.8725.
70%	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	4.1.7. General procedure for the synthesis of compounds 13a-13 L General procedure: The synthetic route of compound 13: take propionyl chloride as anexample, dissolve compound 12 (50 mg, 0.1 mmol) in anhydrousdichloromethane (6 ml), add triethylamine 3 ml of propionyl chlorideslowly at 0 C, then slowly add propionyl chloride (15 mg, 0.16 mmol) toroom temperature, react under the protection of inert gas for 2 h, quenchit with saturated sodium bicarbonate solution at the end of the reaction,extract with ethyl acetate and combine with organic phase anhydrousmagnesium sulfate to dry. The compound 13a was concentrated andseparated by silica gel column chromatography (PE: DCM = 5:1).Compound 13a: White solid, yield 70%; 1H NMR (400 MHz, CDCl3):δH 7.40 (d, J = 2.2 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.16 (dd, J = 8.1,1.8 Hz, 1H), 7.08 (d, J = 2.2 Hz, 1H), 6.51 (d, J = 1.8 Hz, 1H), 5.30 (s,2H), 3.76 (s, 3H), 2.82 (t, J = 8.0 Hz, 1H), 1.77-1.95 (m, 6H), 1.71 (td, J= 6.6, 3.7 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3): δC 176.58 (C),155.40 (C), 153.76 (C), 139.94 (C), 130.71 (CH), 127.43 (CH), 125.44(CH), 124.02 (C), 122.26 (C), 119.18 (C), 118.84 (C), 116.08 (CH),115.60 (CH), 61.01 (CH2), 56.50 (CH3), 43.90 (CH), 30.06 × 2 (CH2),25.86 × 2 (CH2) ppm. HR-ESI-MS: [M + Na]+ calcd. for C20H19Br3NaO4582.8726, found: 582.8725.

Reference： [1]Chen, Xue-Qin; Gao, Zhao-Bing; Gu, Ru-Rong; Guo, Yue-Wei; Jin, Yang; Li, Xu-Wen; Liu, Lai-Xin; Zheng, Yue-Ming [Bioorganic Chemistry, 2022, vol. 126]
[2]Chen, Xue-Qin; Gao, Zhao-Bing; Gu, Ru-Rong; Guo, Yue-Wei; Jin, Yang; Li, Xu-Wen; Liu, Lai-Xin; Zheng, Yue-Ming [Bioorganic Chemistry, 2022, vol. 126]

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Limited Quantity	USD 15-60
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CAS No. :	4524-93-0	MDL No. :	MFCD00001370
Formula :	C₆H₉ClO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WEPUZBYKXNKSDH-UHFFFAOYSA-N
M.W :	132.59	Pubchem ID :	78284
Synonyms :

Signal Word:	Danger	Class:	8,3
Precautionary Statements:	P210-P233-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P363-P370+P378-P403+P235-P405-P501	UN#:	2920
Hazard Statements:	H225-H314	Packing Group:	Ⅱ
GHS Pictogram:

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[ 4524-93-0 ] Synthesis Path-Upstream 1~5

[ 4524-93-0 ] Synthesis Path-Downstream 1~88

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