[ CAS No. 51639-48-6 ] {[proInfo.proName]}

Name: 51639-48-6|1-(4-(Piperazin-1-yl)phenyl)ethanone|98%
Brand: Ambeed
SKU: A857159
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Quality Control of [ 51639-48-6 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 51639-48-6 ]

CAS No. :	51639-48-6	MDL No. :	MFCD00005962
Formula :	C₁₂H₁₆N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KPXVKKBJROCIJB-UHFFFAOYSA-N
M.W :	204.27	Pubchem ID :	97269
Synonyms :

Safety of [ 51639-48-6 ]

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

Application In Synthesis of [ 51639-48-6 ]

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

Upstream synthesis route of [ 51639-48-6 ]
Downstream synthetic route of [ 51639-48-6 ]

[ 51639-48-6 ] Synthesis Path-Upstream 1~3

1
[ 110-85-0 ]
[ 403-42-9 ]
[ 51639-48-6 ]

Yield	Reaction Conditions	Operation in experiment
75.25%	With tetrabutylammomium bromide; potassium carbonate In dimethyl sulfoxide at 80℃; for 15 h; Reflux	Potassium carbonate (2.99 g, 0.02 17 9 mol) was taken in round bottom flask and dried with hot gun under vacuum. Tetra-butylammonium bromide (0.045 g , 0.0014 mol) was added followed by addition of piperazine (1.54 g, 0.018 mol) dissolved in dry dimethyl suiphoxide (5 ml). Reaction mixture was stirred at 80 ° C and then 4- fluoroacetophenone (2 g, 0.0144 mol) was added and reflux was continued for 15 h at same temperature. It was then cooled to room temperature, diluted with water, filtered, filtrate was acidified with dii. HCI, extracted with ethyl acetate and aqueous layer was basified with dii. NaOH. It was then extracted with CHCI3, CHCI3 layer dried over Na2SO4 and concentrated to get pale yellow solid (2.23 g, 75.25 percent, M.P.109°C). ‘H NMR (200 MHz, CDCI3): 6 1.91 (s, IH), 2.52 (s, 3H), 2.98-3.05 (m, 4H), 3.28-3.35 (m, 41]), 6.87 (d, J = 10 Hz, 2H), 7.87 (d, J— 10 Hz, 2H).
41.25%	With potassium carbonate In dimethyl sulfoxide at 190℃; for 12 h; Heating / reflux	5.0 g of 4-fluoroacetophenone (0.036195 moles), 3.11 g of piperazine (0. 036195moles), 5.21 g of potassium carbonate powder (0.037705 moles) and 25 ml dry dimethyl SULPHOXIDE (DMSO) were mixed in a three necked flask equipped with a stirrer, nitrogen inlet, condenser, calcium chloride drying TUBE/NITROGEN outlet and a temperature probe. The mixture was heated to reflux for a total of 12 hours (~190°C) under a constant flow of nitrogen gas. The mixture was then cooled to room temperature and the mixture was filtered to remove the inorganics. A further 100 ml of DMSO was used to wash out the reaction flask. The DMSO solution was then added to 100 g of ice. The mixture obtained was extracted with 3 x 75 ml of dichloromethane. The dichloromethane layers were combined and were washed with 50ML of saturated sodium chloride solution. The dichloromethane layer was then dried using anhydrous magnesium sulphate. The magnesium sulphate was removed by filtration and the dichloromethane was then removed on a rotary evaporator to yield the crude product. 30ML of water was added to the crude product and the mixture was then filtered to recover the product. The product was washed with a further 100 ml of water and then dried in a vacuum oven at 50°C for 4 hours. Product yield 3.05 g (41.25percent) of a yellow/orange solid. The product was analysed by IR, and GC-CIMS.

Reference： [1] Journal of Medicinal Chemistry, 2017, vol. 60, # 13, p. 5507 - 5520
[2] Patent: WO2014/132267, 2014, A1, . Location in patent: Page/Page column 33
[3] Patent: WO2005/7637, 2005, A1, . Location in patent: Page 7-8

2
[ 110-85-0 ]
[ 99-91-2 ]
[ 51639-48-6 ]

Reference： [1] Tetrahedron Letters, 1999, vol. 40, # 31, p. 5655 - 5659

3
[ 99-92-3 ]
[ 334-22-5 ]
[ 51639-48-6 ]

Reference： [1] Tetrahedron Letters, 1997, vol. 38, # 39, p. 6875 - 6876

[ 51639-48-6 ] Synthesis Path-Downstream 1~87

1
[ 78754-94-6 ]
[ 51639-48-6 ]
[ 119784-82-6 ]

Reference： [1]Journal of Pharmaceutical Sciences,1988,vol. 77,p. 735 - 739

2
[ 724428-97-1 ]
[ 51639-48-6 ]
4-(N-4'-acetylphenylpiperazino)-6-dimethylamino-3-methylisoxazolo[5,4-d]pyrimidine [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 68,p. 933 - 947

3
[ 51639-48-6 ]
[ 386230-13-3 ]
C₅₉H₆₅N₃O₁₅ [ No CAS ]

Reference： [1]Journal of Natural Products,2002,vol. 65,p. 1136 - 1142

4
[ 78-84-2 ]
[ 51639-48-6 ]
[ 952281-72-0 ]

Yield	Reaction Conditions	Operation in experiment
80%		Example 12: (E)-N-Hydroxy-3-(4-{(E)-3-[4-(4-isobutyl-piperazin-1 -yl)-phenyl]-3- oxo-propenyl}-phenyl)-acrylamide; STEP A; lsobutylaldehyde (0.230 ml, 2.94 mmol) and Na(CH3CO2)3BH (620 mg, 2.94 mmol) were added at 5C to a solution of 4-piperazino-acetophenone (500 mg,2.45 mmol) in 1 ,2- dichloroethane (10 ml). The resulting mixture was stirred for 4 hours at room temperature. The mixture was then concentrated in vacuo, brought to basic conditions with a5% NaHCO3 solution and extracted with AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo to dryness.The crude product was ground in isopropyl ether, filtered off and then oven dried to obtain 1-[4-(4-isobutyl-piperazin-1-yl)-phenyl]-ethanone. Y = 80%

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 46

5
[ 66885-68-5 ]
[ 51639-48-6 ]
[ 952281-74-2 ]

Yield	Reaction Conditions	Operation in experiment
97%		Example 15: (E)-N-Hydroxy-3-{4-[(E)-3-(4-piperazin-1-yl-phenyl)-3-oxo- propenyl]-phenyl}-acrylamide; STEP A; A solution of 4-piperazino-acetophenone (2 g, 9.8 mmol), 4-formyl cinnamic acid(1.72, 9.8 mmol) and 1.7 M KOH (10 ml) in EtOH (20 ml) and H2O (5 ml) was stirred for 12 hours at room temperature.10% HCI (30 ml) was then added to the mixture and the precipitate was filtered off and dried in vacuo to obtain 3.8 g of (E)-3-{4-[(E)-3-oxo-3-(4-piperazin-1-yl- phenyl)-propenyl]-phenyl}-acrylic acid as hydrochloride.Y = 97%

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 48

6
[ 98-88-4 ]
[ 51639-48-6 ]
[ 717857-64-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In dichloromethane; at 20℃;	Example 16: (E)-3-(4-{(E)-3-[4-(4-Benzoyl-piperazin-1-yl)-phenyI]-3-oxo- propenyl}-phenyl)-N-hydroxy-acrylamide; STEP A; Benzoyl chloride (0.341 ml, 2.94 mmol) was added dropwise to a stirred mixture of 1-(4-piperazin-1-yl-phenyl)-ethanone (500 mg, 2.45 mmol) and TEA (0.681 ml, 4.9 mmol) in DCM (25 ml). The resulting solution was stirred overnight at room temperature, then diluted with DCM and washed with water, with NaHCO3 (5% in H2O) and finally with citric acid (20% in H2O). The organic phase was dried over Na2SO4 and evaporated in vacuo. The resulting solid was triturated with di- isopropylether and filtered to give 687 mg of 1-[4-(4-benzoyI-piperazin-1-yl)- phenyl]-ethanone. Y= 91%

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 61-62

7
[ 917-61-3 ]
[ 51639-48-6 ]
[ 952282-07-4 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In dichloromethane; at 20℃; for 36h;	Example 20: 4-(4-{(E)-3-[4-((E)-2-Hydroxycarbamoyl-vinyI)-phenyl]-acryIoyl}- phenyl)-piperazine-1-carbokappaylic acid amide; STEP A; 1-(4-Piperazin-1-yl-phenyl)-ethanone (500 mg, 2.45 mmol) was dissolved in DCM (20 ml) and NaOCN (318.6 mg, 4.90 mmol) and AcOH (0.28 ml, 4.90 mmol) were added to the resulting solution. The mixture was stirred at room temperature for 36 h and the resulting precipitate was filtered off, washed with DCM and water to give 675 mg of 4-(4-acetyl-phenyl)-piperazine-1-carboxylic acid amide (crude compound was used without further purification in the next step).

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 66

8
[ 100-52-7 ]
[ 51639-48-6 ]
[ 163733-55-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With sodium tris(acetoxy)borohydride; In ethyl acetate; at 20℃;	Example 38: (E)-3-(5-{(E)-3-[4-(4-BenzyI-piperazin-1-yI)-phenyl]-3-oxo- propenyl}-pyridin-2-yl)-N-hydroxy-acrylamide; STEP A; A mixture of 1-(4-piperazin-1-yl-phenyl)-ethanone (500 mg, 2.45 mmol), benzaldehyde (312 mg, 2.94 mmol) and NaBH(OAc)3 (778 mg, 3.67 mmol) in <n="81"/>AcOEt (15 ml) was stirred at room temperature overnight. The resulting solution was partitioned between water and DCM and the organic phase was dried over Na2SO4 and evaporated in vacuo. The crude product was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2) to give 390 mg of 1-[4-(4- benzyl-piperazin-1 -yl)-phenyl]-ethanone. Y= 54%

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 79-80

9
[ 75-07-0 ]
[ 51639-48-6 ]
[ 952282-19-8 ]

Yield	Reaction Conditions	Operation in experiment
44%		Example 41 : (E)-3-(5-{(E)-3-[4-(4-Ethyl-piperazin-1-yl)-phenyI]-3-oxo- propenyI}-pyrdin-2-yl)-N-hydroxy-acryIamide; STEP A; A mixture of 1-(4-piperazin-1-yl-phenyl)-ethanone (500 mg, 2.45 mmol), CH3CHO (161 mg, 3.67 mmol) and NaBH(OAc)3 (778 mg, 3.67 mmol) in DCM (15 ml) was stirred at room temperature overnight. The resulting solution was partitioned between water and DCM and the organic phase was extracted with 1 M HCI. The aqueous layer was brought to basic conditions with NH4OH, extracted with AcOEt and then the organic phase was dried over Na2SO4 and evaporated in vacuo to give 250 mg of 1-[4-(4-ethyl-piperazin-1-yl)-phenyl]-ethanone. Y= 44%

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 82

10
[ 25084-14-4 ]
[ 51639-48-6 ]
1-{4-[4-(5-Nitro-furan-2-carbonyl)-piperazin-1-yl]-phenyl}-ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
540 mg (55%)	In dichloromethane; triethylamine;	1-{4-[4-(5-Nitro-furan-2-carbonyl)-piperazin-1-yl]-phenyl}-ethanone (91). 5-Nitro-furan-2-carbonyl chloride (558 mg, 3.18 mmol) in CH2Cl2 (10 mL) was added to 4-piperazino acetophenone (649 mg, 3.18 mmol) in Et3N (3 mL). The reaction mixture was stirred for 14 hrs at room temperature. The reaction was followed as explained above to yield 540 mg (55%) of compound 91; TLC: Rf 0.68 (ethyl acetate); 1H-NMR (500 MHz, DMSO) delta 2.24 (3H, s), 3.49 (4H, t, J=4.88 Hz), 3.72-3.96 (4H, 2bs), 7.0 (2H, d, J=9.03 Hz), 7.34 (1H, d, J=3.9 Hz), 7.8 (1H, d, J=3.9 Hz), 7.84 (2H, d, J=8.78 Hz); 13C-NMR (300 MHz, DMSO): 26.0, 41.84, 46.3, 112.78, 113.12, 117.22, 126.91, 130.02, 147.47, 151.18, 153.16, 156.69; ESI-Mass: 344 (M+1); Anal. Calcd for C17H17N3O5: C, 59.47; H, 4.99; N, 12.24. Found: C, 59.19; H, 5.08; N, 11.98.

Reference： [1]Patent: US2005/222408,2005,A1

11
[ 4530-20-5 ]
[ 51639-48-6 ]
[ 946523-00-8 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3706 - 3715

12
[ 620-23-5 ]
[ 51639-48-6 ]
C₂₀H₂₂N₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

13
[ 86-81-7 ]
[ 51639-48-6 ]
C₂₂H₂₆N₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

14
[ 99-61-6 ]
[ 51639-48-6 ]
C₁₉H₁₉N₃O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

15
[ 100-52-7 ]
[ 51639-48-6 ]
[ 956699-70-0 ]

Reference： [1]Chemical Communications,2008,p. 1467 - 1469
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

16
[ 104-87-0 ]
[ 51639-48-6 ]
C₂₀H₂₂N₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

17
[ 123-11-5 ]
[ 51639-48-6 ]
C₂₀H₂₂N₂O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

18
[ 104-88-1 ]
[ 51639-48-6 ]
C₄H₉N₂C₆H₄COCHCHC₆H₄Cl [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

19
[ 104-55-2 ]
[ 51639-48-6 ]
C₂₁H₂₂N₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5321 - 5324

20
[ 51639-48-6 ]
C₁₄H₁₉N₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3706 - 3715

21
[ 51639-48-6 ]
C₂₃H₂₄N₄O₄S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3706 - 3715

22
[ 51639-48-6 ]
7-[4-(4-acetyl-phenyl)-piperazin-1-yl]-6-amino-1-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5567 - 5578

23
[ 51639-48-6 ]
[ 1027738-30-2 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5567 - 5578

24
[ 51639-48-6 ]
Isoquinoline-5-sulfonic acid 4-{(S)-3-[4-(4-acetyl-phenyl)-piperazin-1-yl]-2-methylamino-3-oxo-propyl}-phenyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1318 - 1329

25
[ 51639-48-6 ]
[ 516473-21-5 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1318 - 1329

26
[ 51639-48-6 ]
Isoquinoline-5-sulfonic acid 4-{(S)-3-[4-(4-acetyl-phenyl)-piperazin-1-yl]-2-[(isoquinoline-5-sulfonyl)-methyl-amino]-3-oxo-propyl}-phenyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 1318 - 1329

27
[ 51639-48-6 ]
4-(4-acetyl-phenyl)-1,1-dimethyl-piperazin-1-ium; iodide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3946 - 3955

28
[ 51639-48-6 ]
1-{4-[4-(4-amino-phenyl)-piperazin-1-yl]-phenyl}-ethanone [ No CAS ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 5655 - 5659
[2]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 1092 - 1099
[3]Archives of Pharmacal Research,2016,vol. 39,p. 603 - 617

29
[ 51639-48-6 ]
(S)-1-[4-(4-Acetyl-phenyl)-piperazin-1-yl]-2-amino-3-phenyl-propan-1-one; compound with trifluoro-acetic acid [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1991,vol. 64,p. 2519 - 2523

Yield	Reaction Conditions	Operation in experiment
		...nds, the plate was treated with gaseous HF at room temperature for 2 hours. ... N,N,N'-trimethyl-1,3-propanediamine 3,3'-bis(dimethylamino)-dipropylamine 1-(4-nitrophenyl)-piperazine 4-piperazinoacetophenone 3-(aminomethyl)pyridine ethyl 4-amino-1-piperidinecarboxylate thiomorpholine ...
		Examples of heterocylic amines corresponding to heterocyclic amine rings according to --NR9 R10 are: ... pipecolic acid, 3-piperidine ethanol, 2-piperidine ethanol, 1-piperazine propanol, p-piperazinoacetophenone, 4-phenyl-1,2,3,6-tetrahydropyridine, 4-phenylpiperidine, proline, ...
		Examples of heterocylic amines corresponding to heterocyclic amine rings according to -NR9 N10 are: ... pipecolic acid, 3-piperidine ethanol, 2-piperidine ethanol, 1-piperazine propanol, p-piperazinoacetophenone, 4-phenyl-1,2,3,6-tetrahydropyridine, 4-phenylpiperidine, proline, ...

Additional primary amines suitable for the process of the invention are those represented by the following formulae: ... n-(3-trifluoromethylphenyl)piperazine 1-(4-fluorophenyl)piperazine 1-(4-nitrophenyl)piperazine 4-piperazinoacetophenone 1-ethoxycarbonylpiperazine 1-(4-chlorobenzhydryl)piperazine n-methylpiperazine ...

31
2-chloro-1-(3,4-dihydroxy-5-nitro-phenyl)-ethanone [ No CAS ]
[ 51639-48-6 ]
2-[4-(4-acetyl-phenyl)-piperazin-1-yl]-1-(3,4-dihydroxy-5-nitro-phenyl)-ethanone dihydrochloride [ No CAS ]

Reference： [1]Patent: EP1167342,2002,A1 .Location in patent: Example 80

32
[ 539-74-2 ]
[ 51639-48-6 ]
[ 435270-84-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In ethanol;	1. Synthesis of 3-[4-(4-acetylphenyl)-1-piperazinyl]propionic Acid The reaction mixture 1-[4-(4-acetylphenyl)]piperazine (408 mg, 2.0 mmol), ethyl 3-bromopropionate (500 mg, 2.7 mmol), sodium bicarbonate (300 mg, 3.5 mmol) and ethanol (15 ml) was refluxed for 6 h till the amine disappeared completely. After the mixture was filtered, the resulting solid was dissolved in 5 ml dioxane and 14 ml 5% sodium hydroxide solution.
	With sodium hydrogencarbonate; In ethanol;	1. Synthesis of 3-[4-(4-acetylphenyl)-1-piperazinyl]propionic acid The reaction mixture 1-[4-(4-acetylphenyl)]piperazine (408 mg, 2.0 mmol), ethyl 3-bromopropionate (500 mg, 2.7 mmol), sodium bicarbonate (300 mg, 3.5 mmol) and ethanol (15 ml) was refluxed for 6 h till the amine disappeared completely. After the mixture was filtered, the resulting solid was dissolved in 5 ml dioxane and 14 ml 5% sodium hydroxide solution.
		1. Synthesis [OF 3- [4- (4-ACETYLPHENYL)-1-PIPERAZINYL] PROPIONIC] acid [[0149]] The reaction mixture [1- [4- (4-ACETYLPHENYL)]] piperazine (408 mg, 2.0 mmol), ethyl 3- bromopropionate (500 mg, 2.7 mmol), sodium bicarbonate (300 mg, 3.5 mmol) and ethanol (15 ml) was refluxed for 6 h till the amine disappeared completely. After the mixture was filtered, the resulting solid was dissolved in 5 ml dioxane and 14 ml 5% sodium hydroxide solution. The mixture was stirred at room temperature overnight, then it was acidified with concentrated hydrogen chloride. Solid was filtered and washed with water, and then dried to give 330 mg [3- [4- (4-ACETYLPHENYL)-L-PIPERAZINYL]] propionic acid, mp [204-206C.] [0150] The chemical structure analysis was performed [BY'HNNM (DMSO-D6, 600NMZ)] : [6] 7.86 (d, 2H, Ar-H), 7.07 (d, 2H, Ar-H), 3.40-3. 32 [(M,] [10H, NCH2),] 2.82 (t, 2H, [COCH2),] 2. 48 (s, 3H, COCH3).

Reference： [1]Patent: US2003/32624,2003,A1
[2]Patent: US6403604,2002,B1
[3]Patent: WO2003/101998,2003,A1 .Location in patent: Page 55-57

33
C₂₄H₂₀Br₂N₂O₄ [ No CAS ]
[ 51639-48-6 ]
C₂₁H₂₄Br₂N₄O₂ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 159

34
[ 638189-59-0 ]
[ 51639-48-6 ]
(2S)-3-(4-{2-[4-(4-acetyl-phenyl)-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-2-methoxy-propionic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The title compound was prepared from [(2S)-3- (4-CARBOXYMETHOXY-PHENYL)-2-] methoxy-propionic acid ethyl ester (PREPARATION 3, step 2) and [1- (4-PIPERAZIN-1-YL-] phenyl) -ethanone via the same procedure used for the preparation of (2S, [LR)-2-ETHOXY-] 3- [{1-[2-(4-PHENOXY-PHENYL)-ETHYLCARBAMOYL]-ETHOXY}-PHENYL)-PROPIONIC] acid (Example 1, step 3) to produce a colorless oil. MS (ES) for [C24H2SN206] [[M+H] +] : 441.

Reference： [1]Patent: WO2004/789,2003,A1 .Location in patent: Page 103

35
[ 3454-29-3 ]
[ 51639-48-6 ]
C₅₁H₇₄N₆O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.54%	In toluene; for 4h;Heating / reflux;	8.11 g Piperazinoacetophenone (0.0396864 moles), 4.00 g trimethylolpropane triglycidyl ether (0.0132288 moles) and toluene 50 ml were mixed in a two-necked flask fitted with a condenser, stirrer and temperature probe. The mixture was heated to reflux for a total of 4 hours. The mixture was then cooled and filtered and then the solvent was removed on a rotary evaporator to yield the product. Product yield 11. 57 g (95.54%) of a viscous slightly yellow liquid. The product was analysed by IR, HPLC and LCMS.

Reference： [1]Patent: WO2005/7637,2005,A1 .Location in patent: Page 10

36
[ 106-75-2 ]
[ 51639-48-6 ]
C₃₀H₃₈N₄O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In toluene; at 42℃; for 2h;	5.0 g OF 4-PIPERAZINOACETOPHENONE (0.02451 moles), 2.48 g of triethylamine (0.02451 moles) and 75 ml of toluene were mixed in a two necked flask equipped with a stirrer, condenser and a temperature probe. 2. 635 g of diethylene glycol chloroformate (0. 012255 moles) in 20 ml of toluene were then added slowly, ensuring the exotherm was controlled (temperature maximum throughout the addition was 42C). After the addition was complete, the mixture was stirred for 2 hours, allowing the mixture to cool to room temperature. The mixture was then filtered to remove the insoluble triethylamine hydrochloride formed during the reaction. The toluene was then removed on a rotary evaporator to yield the product Product yield 6.78 g of a white solid. The product was analysed by IR, HPLC and LCMS.

Reference： [1]Patent: WO2005/7637,2005,A1 .Location in patent: Page 14-15

37
[ 110-85-0 ]
[ 403-42-9 ]
[ 51639-48-6 ]

Yield	Reaction Conditions	Operation in experiment
75.25%	With tetrabutylammomium bromide; potassium carbonate; In dimethyl sulfoxide; at 80℃; for 15h;Reflux;	Potassium carbonate (2.99 g, 0.02 17 9 mol) was taken in round bottom flask and dried with hot gun under vacuum. Tetra-butylammonium bromide (0.045 g , 0.0014 mol) was added followed by addition of piperazine (1.54 g, 0.018 mol) dissolved in dry dimethyl suiphoxide (5 ml). Reaction mixture was stirred at 80 C and then 4- fluoroacetophenone (2 g, 0.0144 mol) was added and reflux was continued for 15 h at same temperature. It was then cooled to room temperature, diluted with water, filtered, filtrate was acidified with dii. HCI, extracted with ethyl acetate and aqueous layer was basified with dii. NaOH. It was then extracted with CHCI3, CHCI3 layer dried over Na2SO4 and concentrated to get pale yellow solid (2.23 g, 75.25 %, M.P.109C). ?H NMR (200 MHz, CDCI3): 6 1.91 (s, IH), 2.52 (s, 3H), 2.98-3.05 (m, 4H), 3.28-3.35 (m, 41]), 6.87 (d, J = 10 Hz, 2H), 7.87 (d, J- 10 Hz, 2H).
55%		The piperazine (6 g, 69 mmol) was dissolved in 30 mL DMF was added potassium carbonate (9.51 g, 69mmol), and after stirring for 15 minutes, Add p-fluoroacetophenone (3.2 g, 2.298 mmol) to the mixture, and reflux at 80 C for overnight. After the reaction was completed, the solvent was removed under reduced pressure, and the dichloromethane was dissolved, washed with saturated sodium chloride, and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure to obtain CBP-1, yield: 55%;
41.25%	With potassium carbonate; In dimethyl sulfoxide; at 190℃; for 12h;Heating / reflux;	5.0 g of 4-fluoroacetophenone (0.036195 moles), 3.11 g of piperazine (0. 036195moles), 5.21 g of potassium carbonate powder (0.037705 moles) and 25 ml dry dimethyl SULPHOXIDE (DMSO) were mixed in a three necked flask equipped with a stirrer, nitrogen inlet, condenser, calcium chloride drying TUBE/NITROGEN outlet and a temperature probe. The mixture was heated to reflux for a total of 12 hours (~190C) under a constant flow of nitrogen gas. The mixture was then cooled to room temperature and the mixture was filtered to remove the inorganics. A further 100 ml of DMSO was used to wash out the reaction flask. The DMSO solution was then added to 100 g of ice. The mixture obtained was extracted with 3 x 75 ml of dichloromethane. The dichloromethane layers were combined and were washed with 50ML of saturated sodium chloride solution. The dichloromethane layer was then dried using anhydrous magnesium sulphate. The magnesium sulphate was removed by filtration and the dichloromethane was then removed on a rotary evaporator to yield the crude product. 30ML of water was added to the crude product and the mixture was then filtered to recover the product. The product was washed with a further 100 ml of water and then dried in a vacuum oven at 50C for 4 hours. Product yield 3.05 g (41.25%) of a yellow/orange solid. The product was analysed by IR, and GC-CIMS.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5507 - 5520
[2]Patent: WO2014/132267,2014,A1 .Location in patent: Page/Page column 33
[3]Analytical Chemistry,2019,vol. 91,p. 11397 - 11402
[4]Patent: CN110590762,2019,A .Location in patent: Paragraph 0025
[5]Patent: WO2005/7637,2005,A1 .Location in patent: Page 7-8

38
[ 51639-48-6 ]
C₁₂H₁₈N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e (1.00 g, 4.9 mmol) in EtOH (15 ml) add NaBH4 (0.93 g, 25 mmol). Heat at reflux 4 h, allow to cool, and add 0.5N NaOH (20 ml). Extract with CH2Cl2, dry over MgSO4, concentrate, and chromatograph over silica to obtain the title alcohol as a white solid.

Reference： [1]Patent: US2005/239795,2005,A1 .Location in patent: Page/Page column 13

39
[ 291512-72-6 ]
[ 51639-48-6 ]
[ 291510-27-5 ]

Yield	Reaction Conditions	Operation in experiment
71.5%		EXAMPLE 17) 1-[(5,6-Dimethyl-2-methoxypyrazin-3-yl)aminocarbonyl]-4-(4-acetylphenyl)piperazine Phenyl N-(5,6-dimethyl-2-methoxypyrazin-3-yl)carbamate and <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e were reacted by the same way with the example 1 to obtain the titled compound. Yield: 71.5%

Reference： [1]Patent: US2003/92910,2003,A1

40
phenyl N-(2-methoxyquinoxalin-3-yl)thiocarbamate [ No CAS ]
[ 51639-48-6 ]
[ 291510-81-1 ]

Yield	Reaction Conditions	Operation in experiment
56.9%		EXAMPLE 70) 1-[(2-Methoxyquinoxalin-3-yl)aminothiocarbonyl]-4-(4-acetylphenyl) piperazine Phenyl N-(2-methoxyquinoxalin-3-yl)thiocarbamate and <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e were reacted by the same way with the example 63 to obtain the titled compound. yield: 56.9%

Reference： [1]Patent: US2003/92910,2003,A1

41
[ 24424-99-5 ]
[ 51639-48-6 ]
3-(4-(4-t-butoxycarbonylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;	Step 1. Preparation of 3-(4-(4-t-butoxycarbonylpiperazino)phenyl)-5-(morpholinocarbamoylamino)indeno[1,2-c]pyrazol-4-one Synthesis of 30 To a suspension of 139 g (680 mmol) of 4-piperazinoacetophenone in 700 mL of tetrahydrofuran at 25 C. was added slowly over 20 min. a solution of 157 g (720 mmol) of di-tert-butyl dicarbonate in 300 mL of tetrahydrofuran. The resulting mixture was refluxed for 15 h. After cooling the mixture was filtered, and the filtrate was concentrated under vacuum to provide an off-white solid. This crude product was recrystallized from diethyl ether/hexane to afford 192 g of the 30 as a white solid. NMR (CDCl3) delta 7.89 (d, 2H, J=9 Hz), 6.87 (d, 2H, J=9 Hz), 3.59 (m, 4H), 3.33 (m, 4H), 2.53 (s, 3H), 1.49 (s, 9H).

Reference： [1]Patent: US2001/27195,2001,A1

42
[ 24424-99-5 ]
[ 51639-48-6 ]
tert-butyl 4-(4-acetylphenyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In dichloromethane; at 20℃;	Preparation 9: 4-(4-Acetyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester; A mixture of 1-(4-piperazin-1-yl-phenyl)-ethanone (513 mg, 2.51 mmol), BOC2O (820 mg, 3.76 mmol) and TEA (0.698 ml, 5.02 mmol) in DCM (20 ml) was stirred at room temperature overnight. The resulting solution was concentrated in vacuo and then partitioned between water and AcOEt. The organic phase was dried over Na2SO4, evaporated in vacuo and the crude reaction mixture was purified by column chromatography (eluent: petroleum ether/AcOEt) to give 701 mg of 4-(4- acetyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester. <n="59"/>Y= 92%
55%	In dichloromethane; at 20℃;	Example A20; a) Preparation of intermediate 56; C,C'-bis(l,l-dimethylethyl) dicarbonic acid ester (60.1 g; 0.276 mol) was added in small portions to a stirred solution of l-[4-(l-piperazinyl)phenyl]ethanone (50.0 g; 0.245 mol) in dry CH2Cl2 (400 ml) at room temperature. The obtained solution was stirred for 0.5 hour. The solvent was removed in vacuum. The residue was purified by chromatography (eluent: chloroform), yielding 40.7 g (55 %) of intermediate 56.
10.9 g (73%)	With potassium carbonate; In tetrahydrofuran; water;	Preparation 68 N-t-butyloxycarbonyl-4-piperazinoacetophenone A solution of the 4-piperazinoacetophenone (10 g, 49 mmol) in tetrahydrofuran:water (200 ml, 1:1 mixture) was treated with potassium carbonate (8.43 g, 58 mmol) and di-t-butyl dicarbonate (13.1 g, 53.9 mmol). The reaction mixture was stirred at room temperature for 3 h. Water (300 ml) was added to the mixture and organic was extracted with ethyl acetate (3100 ml). The combined organic fraction was washed with water (2200 ml), brine (100 ml), dried over sodium sulfate, and concentrated in vacuo to 17. 41 g of the yellowish solid. The crude product was further purified by Prep LC 2000 eluding with 30% EtOAc:Haxanes to give 10.9 g (73%) of the title compound as a white solid. Field Desorption Mass Spectrum: M+=305.

Reference： [1]Patent: WO2007/113249,2007,A2 .Location in patent: Page/Page column 57-58
[2]Patent: WO2008/148840,2008,A1 .Location in patent: Page/Page column 81
[3]Patent: US6303816,2001,B1

43
[ 130634-04-7 ]
[ 51639-48-6 ]
1,3-dimethyl-6-[2-(4-[4-acetylphenyl]piperazin-1-yl)ethylamino]-2,4(1H,3H)-pyrimidinedione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform;	EXAMPLE 46 Synthesis of 1,3-dimethyl-6-[2-(4-[4-acetylphenyl]-piperazin-1-yl)ethylamino]-2,4(1H,3H)-pyrimidinedione.oxalate (Compound 104) STR109 A mixture of 1.6 g of <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e and 1.1 g of 1,3-dimethyl-6-[2-(p-toluenesulfonyloxy)-ethylamino]-2,4(1H,3H)-pyrimidinedione was heated at 80 C. for 6 hours, and after standing for cooling, the reaction solution was poured into a 5% aqueous sodium carbonate solution, stirred and then extracted with chloroform. The chloroform solution was washed with water and then concentrated, and the resultant residue was purified through a silica gel column chromatograph (chloroform/methanol=50/1 in volume ratio), thereby obtaining 0.5 g of 1,3-dimethyl-6-[2-(4-[4-acetylphenyl]piperazin-1-yl)ethylamino]-2,4(1H,3H)-pyrimidinedione. Analytical results of the obtained pyrimidinedione derivative 1 H-NMR (CD3 OD) delta ppm: 2.55 (s, 3H), 2.4-3.0 (m, 10H), 3.0-3.2 (m, 2H), 3.33 (s, 3H), 3.38 (s, 3H), 4.83 (s, 1H), 5.56 (s, 1H), 6.92 (d, 2H), 7.86 (d, 2H).

Reference： [1]Patent: US5332739,1994,A

44
phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate [ No CAS ]
[ 51639-48-6 ]
1-[(5-ethyl-2-methoxy-6-methylpyridin-3-yl)aminocarbonyl]-4-(4-acetylphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%		Example 34 1-[(5-ethyl-2-methoxy-6-methylpyridin-3-yl)aminocarbonyl]-4-(4-acetylphenyl)piperazine Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e were reacted by the same way with the example 1 to obtain the titled compound. yield: 67%

Reference： [1]Patent: US5780472,1998,A

45
2-propanol-water [ No CAS ]
[ 75-09-2 ]
[ 108-00-9 ]
[ 530-62-1 ]
[ 51639-48-6 ]
[ 117546-53-9 ]

Yield	Reaction Conditions	Operation in experiment
2.0 g (19%)	In tetrahydrofuran; ethereal hydrogen chloride;	EXAMPLE 34 4-(4-Acetylphenyl)-N-[2-(dimethylamino)ethyl]-1-piperazinecarboxamide monohydrochloride. This compound was prepared according to the procedure used to synthesize the compound of Example 11. A mixture of 4.9 g (0.03 mole) of 1,1'-carbonyldiimidazole, 2.5 g (0.03 mole) of unsym-dimethylethylenediamine and 6.1 g (0.03 mole) of 4-piperazinoacetophenone in a total volume of 200 ml of tetrahydrofuran gave an oil as residue. The oil was eluted through a 200 g silica gel column with an 80% methylene chloride-19.8% methanol-0.2% ammonium hydroxide mixture. The product fractions were concentrated under reduced pressure to give an oil which was partitioned between water and chloroform. The chloroform layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to an oil. The hydrochloride was formed in ethereal hydrogen chloride and the solid recrystallized from methanol-diethyl ether to give 3.7 g of product as a yellow solid. The product was recrystallized again from 2-propanol-water to give 2.0 g (19%) of the title compound as a light cream solid, m.p. 221-223 C. Analysis: Calculated for C17 H27 ClN4 O2: C,57.54; H,7.67; N,15.79 Found: C,57.25; H,7.72; N,15.53

Reference： [1]Patent: US4960776,1990,A

46
[ 51639-48-6 ]
[ 13999-24-1 ]
5-[2-[4-(4-Acetylphenyl)-1-piperazinyl]ethyl]-3-methyl-2-oxazolidinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.3 g (80%)	With potassium iodide; sodium carbonate; In butan-1-ol;	EXAMPLE 9 5-[2-[4-(4-Acetylphenyl)-1-piperazinyl]ethyl]-3-methyl-2-oxazolidinone This compound was prepared according to the procedure of Example 2. A mixture of 4.1 g (0.02 mol) of 4-(1-piperazino)acetophenone (94%, Aldrich), 3.3 g (0.02 mol) of 5-(2-chloroethyl)-3-methyl-2-oxazolidinone, 6.4 (0.06 mol) of anhydrous sodium carbonate and 0.4 g of potassium iodide in 100 mL of 1-butanol gave 5.3 g (80%) of yellow solid, mp 142-145 C. (2-propanol). Anal. Calculated for C18 H25 N3 O2: C, 65.24; H, 7.60; N, 12.68. Found C, 65.42; H, 7.77; N, 12.46.

Reference： [1]Patent: US5086055,1992,A

47
[ 140691-20-9 ]
[ 51639-48-6 ]
4-(4-(4-(4-acetylphenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane;	EXAMPLE 46 Synthesis of 4-(4-(4-(4-acetylphenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine -3,5-dione STR58 A 100 mg amount of the compound of Example 7 was dissolved in 10 ml of dioxane, and 216 mg (3 equivalents) of 94% 4-piperazinoacetophenone was added, followed by heating under stirring at 100 C. for hours. The reaction treatment was conducted as in Example 19 and purification as in Example 21, to give mg of the desired compound (yield 72%). The hydrochloride was obtained by forming the hydrochloride in a conventional manner, followed by recrystallization from methylene chloride-ether.

Reference： [1]Patent: US5071845,1991,A

48
[ 91561-73-8 ]
[ 51639-48-6 ]
3-[2-(4-p-acetylphenylpiperazin-1-yl)ethoxy]-p-cymene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.5%	With sodium chloride; sodium hydrogencarbonate;	1. Preparation of 3-[2-(4-p-acetylphenylpiperazin-1-yl)ethoxy]-p-cymene. The following are introduced into a 100 ml three-necked flask fitted with a condenser, a magnetic stirrer and a thermometer: 21.27 g (0.1 mol) of 3-(2-chloroethoxy)-p-cymene 40.85 g (0.2 mol) of p-piperazinylacetophenone The mixture is heated at 145 C. for 1 hour. After cooling to room temperature, the reaction medium is poured into a 10% solution of sodium bicarbonate. The aqueous phase obtained is extracted twice with 100 ml of methylene chloride. The combined organic phases are washed with a saturated aqueous solution of sodium chloride. They are then dried over sodium sulfate. After filtration, the solvent is driven off under vacuum to give 59.3 g of crude product. This is topped by fractional distillation under vacuum (under nitrogen). 27.66 g of a residue are isolated and recrystallized from a 5/2 IPA/ethanol mixture. This gives 11.22 g of beige crystals (yield=29.5%); m.p.KB =90-92 C.; GC purity >99%; perchloric titer=102%; IR: consistent with the proposed structure.

Reference： [1]Patent: US5110816,1992,A

49
[ 88-10-8 ]
[ 51639-48-6 ]
1-(4-acetylphenyl)-4-diethylcarbamoylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In chloroform;	Example 8 [1-(4-acetylphenyl)-4-diethylcarbamoylpiperazine and its hydrochloride] In 50 ml of chloroform was dissolved 10.2 g (0.05 mole) of 1-(4-acetylphenyl)-piperazine at room temperature, and 6.8 g (0.05 mole) of diethylcarbamoyl chloride was dropped to the solution over a period of 30 minutes. The mixture was stirred at room temperature for 5 hours, and the insoluble substance was removed. The filtrate was subjected to distillation under reduced pressure and the residue was made alkaline by 4 N aqueous solution of sodium hydroxide and extracted with 100 ml of toluene. The organic layer was dried with anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was recrystallized from a benzene-hexane mixed solvent to obtain 1-(4-acetylphenyl)-4-diethylcarbamoylpiperazine having a boiling point of 72 to 76 C.

Reference： [1]Patent: US4446133,1984,A

50
[ 39662-63-0 ]
[ 7440-44-0 ]
[ 51639-48-6 ]
5-[4-(4-acetylphenyl)piperazin-1-yl]pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide;potassium hydroxide; In di-isopropyl ether; butan-1-ol;	EXAMPLE 8 A mixture of 5-ethoxypyrrolidin-2-one (7.75 g) and <strong>[51639-48-6]1-(4-acetylphenyl)piperazin</strong>e (12.26 g) is heated for 1 hour 40 minutes at a temperature between 126 C. and 140 C., with stirring, the ethanol formed being distilled off. After the reaction mixture has cooled, the solid obtained is filtered off, washed 3 times with ethyl acetate (20 cc in total) and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 C. in the presence of potassium hydroxide pellets. This gives a crude product (15.6 g) melting at 210 C. This product is dissolved in boiling butanol (80 cc); the solution is treated with decolorising charcoal (1 g) and filtered hot. The filtrate is cooled at a temperature of about 4 C. for 16 hours. The resulting crystals are filtered off, washed twice with butanol (20 cc in total) cooled to a temperature of about 4 C. and then 3 times with diisopropyl ether (60 cc in total), and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 C. in the presence of potassium hydroxide pellets. This gives a product (12.1 g) melting at 210 C. This product (11.5 g) is taken up in a 0.5N aqueous solution of hydrochloric acid (80 cc). The solution is treated with decolorising charcoal (1 g) and filtered; the filtrate is cooled to a temperature of about 4 C. and rendered alkaline with a normal aqueous solution of sodium hydroxide (50 cc). After 10 minutes at a temperature of about 4 C., the resulting crystals are filtered off, washed 3 times with distilled water (30 cc in total) cooled to a temperature of about 4 C., and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 C. in the presence of potassium hydroxide pellets. This gives a product (9.7 g) melting at 180 C. This product is dissolved in boiling butanol (80 cc) and the solution obtained is treated with decolorising charcoal (1 g) and filtered hot. The filtrate is cooled at a temperature of about 4 C. for 1 hour. The resulting crystals are filtered off, washed twice with butanol (20 cc in total) and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20 C. in the presence of potassium hydroxide pellets. This gives 5-[4-(4-acetylphenyl)piperazin-1-yl]pyrrolidin-2-one (6.7 g) in the form of yellow crystals melting at 199 C.

Reference： [1]Patent: US4547504,1985,A

51
[ 530-62-1 ]
[ 51639-48-6 ]
[ 852840-40-5 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; for 24h;Heating / reflux;	To a suspension of CDI (60 mmol) in THF (100 mL) is added l-(4-piperazin-l-yl-phenyl)- ethanone (55 mmol). The mixture is refluxed for 24 hours before cooling to rt. The solvent is removed. The residue is dissolved in DCM (100 mL), and washed with water (2 x 50 mL). The organic layer is dried over MgStheta4 and solvent removed to give the title compound, which is used in the next step reaction without further purification.

Reference： [1]Patent: WO2007/16496,2007,A2 .Location in patent: Page/Page column 60

52
[ 1057319-10-4 ]
[ 51639-48-6 ]
2-[4-(4-acetyl-phenyl)-piperazin-1-yl]-1-(4-cyclopentyl-piperazin-1-yl)-ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 20℃;	A mixture of 2-bromo-l-(4-cyclopentyl-piperazin-l-yl)-ethanone (1.2 mmol), l-(4-piperazin- l-yl-phenyl)-ethanone (1.2 mmol) and potassium carbonate (2.4 mmol) in acetonitrile (10 mL) is stirred at rt overnight. The solvent is removed in vacuo and to the residue is added DCM (40 mL) and aqueous sodium bicarbonate (15 mL). The layers are separated and aqueous layer is extracted withDCM (15 mL). The combined organic layers are dried (MgSC^) and solvent removed in vacuo to give the crude product, which is purified by PTLC (5% MeOH in DCM) to give the title compound. 1H NMR (CDCl3) delta 7.86 (d, 2H), 6.86 (d, 2H), 3.66-3.60 (m, 4H), 3.36 (t, 4H), 3.23 (s, 2H), 2.65 (t,4H), 2.51 (s, 3H), 2.50-2.44 (m, 5H), 1.89-1.80 (m, 2H), 1.73-1.63 (m, 2H), 1.61-1.48 (m, 2H), 1.44-1.32 (m, 2H); LC-MS (M+l) 399.35.

Reference： [1]Patent: WO2007/16496,2007,A2 .Location in patent: Page/Page column 50

53
[ 539-74-2 ]
[ 51639-48-6 ]
[ 1061704-03-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2570 - 2578

54
[ 2969-81-5 ]
[ 51639-48-6 ]
[ 1061702-65-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2570 - 2578

55
[ 109-70-6 ]
[ 51639-48-6 ]
C₁₅H₂₁ClN₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 5405 - 5412

56
[ 50-00-0 ]
[ 93-35-6 ]
[ 51639-48-6 ]
[ 1024743-09-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2591 - 2605

57
[ 50-00-0 ]
[ 90-33-5 ]
[ 51639-48-6 ]
[ 1024743-10-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2591 - 2605

58
[ 10200-59-6 ]
[ 51639-48-6 ]
C₂₈H₃₃N₅O₂S [ No CAS ]

Reference： [1]Chemical Communications,2008,p. 1467 - 1469

59
[ 956699-70-0 ]
[ 51639-48-6 ]
C₃₁H₃₆N₄O₂ [ No CAS ]

Reference： [1]Chemical Communications,2008,p. 1467 - 1469

60
[ 26934-35-0 ]
[ 108-24-7 ]
[ 51639-48-6 ]
[ 1023617-90-4 ]
[ 1023617-91-5 ]
C₄₀H₄₈N₆O₃ [ No CAS ]

Reference： [1]Chemical Communications,2008,p. 1467 - 1469

61
[ 26934-35-0 ]
[ 51639-48-6 ]
C₃₆H₄₇N₅O₃ [ No CAS ]

Reference： [1]Chemical Communications,2008,p. 1467 - 1469

62
[ 20672-18-8 ]
[ 51639-48-6 ]
[ 1079286-70-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 8447 - 8465

63
[ 5176-28-3 ]
[ 51639-48-6 ]
[ 1100051-35-1 ]
[ 1072849-54-7 ]

Reference： [1]Organic Letters,2008,vol. 10,p. 4723 - 4726

64
[ 106-94-5 ]
[ 51639-48-6 ]
[ 56915-76-5 ]

Yield	Reaction Conditions	Operation in experiment
87.5%	With triethylamine; In acetonitrile; for 18h;Reflux;	2.0 g (0.0098 mol) of 1-(4-(piperazin-1-yl)phenyl)ethanone was dissolved in 40 ml of dry acetonitrile. Then 1.77 ml (0.0196 mol) of propyl bromide was added followed by the addition of 4.24 ml (0.029 mol) of triethyl amine. The reaction mixture was refluxed for 18 h. After completion of reaction, the content was allowed to cool to room temperature and acetonitrile was removed on rotavapor. The crude product was washed with 5 % ethyl acetate in pet-ether to get 2.1 gm (87.50 %) 1-(4-(4-propylpiperazin-1-yI) phenyl) ethanone as a off-white solid. 1H NMR (200 MHz, CDC13): oe 0.93 (t, .1 = 7 Hz, 3H), 1.45-1.65 (m, 2H), 2.30-2.42 (m, 2H), 2.51 -2.62 (m, 7 H), 3.37 (t, J 6Hz, 4H),6.87 (d, J 10 Hz, 2H), 7.87 (d, J 10 Hz, 2H).

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 3892 - 3901
[2]Patent: WO2014/132267,2014,A1 .Location in patent: Page/Page column 34

65
[ 501-30-4 ]
[ 50-00-0 ]
[ 51639-48-6 ]
[ 1225273-10-8 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2010,vol. 60,p. 22 - 29

66
[ 1174392-74-5 ]
[ 51639-48-6 ]
[ 893786-87-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1767 - 1770

67
[ 1174392-68-7 ]
[ 51639-48-6 ]
[ 904587-18-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1767 - 1770

68
rac-5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)benzoic acid [ No CAS ]
[ 51639-48-6 ]
[ 1229627-96-6 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4603 - 4614

69
C₁₈H₂₃N₂O₇PolS [ No CAS ]
[ 51639-48-6 ]
C₃₀H₃₇N₄O₇PolS [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3561 - 3564

70
[ 1263291-58-2 ]
[ 51639-48-6 ]
C₄₄H₇₂N₄O₁₂ [ No CAS ]
C₄₄H₇₂N₄O₁₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 5868 - 5880

71
[ 573-57-9 ]
[ 51639-48-6 ]
(1R,2R)-(+)-1-{4-[4-(1-hydroxy-1,2-dihydronaphthalen-2-yl)piperazin-1-yl]phenyl}ethanone [ No CAS ]