Name: 5308-28-1|1-Isobutylpiperazine|98%
Brand: Ambeed
SKU: A681007
Price: 9.0 USD
Availability: InStock
Rating: 98 (40 reviews)

1
[ 110-85-0 ]
[ 78-77-3 ]
[ 5308-28-1 ]

Yield	Reaction Conditions	Operation in experiment
44%	With triethylamine In ethanol for 72h; Heating;
	With toluene at 90℃;

Reference： [1]Yamane; Hashizume; Yamashita; Konishi; Hosoe; Hidaka; Watanabe; Kawaharada; Yamamoto; Kuze [Chemical and Pharmaceutical Bulletin, 1993, vol. 41, # 1, p. 148 - 155]
[2]Morren et al. [Industrie Chimique Belge, 1957, vol. 22, p. 409,416]

2
[ 5308-28-1 ]
[ 17799-88-1 ]
[ 113649-37-9 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene

Reference： [1]Hromatka et al. [Monatshefte fur Chemie, 1957, vol. 88, p. 56,62]

3
[ 5308-28-1 ]
[ 110154-27-3 ]
[ 124117-84-6 ]

Reference： [1]Hromatka et al. [Monatshefte fur Chemie, 1957, vol. 88, p. 234,238]

4
[ 110-85-0 ]
[ 78-77-3 ]
[ 5308-28-1 ]
[ 113900-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol for 28h; Heating;

Reference： [1]Marsella, John A. [Journal of Organometallic Chemistry, 1991, vol. 407, # 1, p. 97 - 105]

5
[ 5308-28-1 ]
[ 22117-85-7 ]
[ 102535-28-4 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 1814 - 1820

6
[ 5308-28-1 ]
[ 130288-93-6 ]
N-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7yloxy)propyl]-4-(2-methylpropyl)-1-piperazinecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With diphenylphosphoranyl azide; triethylamine 1.) DMF, 130 deg C, 2 h, 2.) NMP, 200 deg C, 30 min; Multistep reaction;

Reference： [1]Meanwell, Nicholas A.; Hewawasam, Piyasena A.; Thomas, Jeanine; Wright, J. J. Kim; Russell, John W.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 22, p. 3251 - 3264]

7
[ 5308-28-1 ]
[ 102359-00-2 ]
[ 102358-81-6 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 2253 - 2258

8
[ 5308-28-1 ]
[ 99615-68-6 ]
[ 99615-58-4 ]

Yield	Reaction Conditions	Operation in experiment
23%	With diethyl cyanophosphonate; triethylamine In N,N-dimethyl-formamide 1.) 0-5 deg C, 30 min; 2.) rt, 1.5 h;

Reference： [1]Ogawa; Tamada; Fujioka; Teramoto; Kondo; Yamashita; Yabuuchi; Tominaga; Nakagawa [Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 6, p. 2253 - 2258]

9
[ 5308-28-1 ]
[ 143526-61-8 ]
[ 129791-92-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With manganese(IV) oxide In dimethyl sulfoxide for 24h; Ambient temperature;

Reference： [1]Yamane; Hashizume; Yamashita; Konishi; Hosoe; Hidaka; Watanabe; Kawaharada; Yamamoto; Kuze [Chemical and Pharmaceutical Bulletin, 1993, vol. 41, # 1, p. 148 - 155]

10
[ 5308-28-1 ]
[ 93107-30-3 ]
1-Cyclopropyl-6-fluoro-7-(4-isobutyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 729 - 735

11
[ 5308-28-1 ]
[ 103995-01-3 ]
1-(2,4-Difluoro-phenyl)-6-fluoro-7-(4-isobutyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In acetonitrile for 17h; Heating;

Reference： [1]Renau; Sanchez; Gage; Dever; Shapiro; Gracheck; Domagala [Journal of Medicinal Chemistry, 1996, vol. 39, # 3, p. 729 - 735]

12
[ 1026893-83-3 ]
[ 5308-28-1 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid for 16h; Ambient temperature;

Reference： [1]Renau; Sanchez; Gage; Dever; Shapiro; Gracheck; Domagala [Journal of Medicinal Chemistry, 1996, vol. 39, # 3, p. 729 - 735]

13
[ 5308-28-1 ]
[ 198210-90-1 ]
6-{4-[2-(4-Isobutyl-piperazin-1-yl)-ethyl]-phenyl}-pyridin-2-ylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium iodide In N,N-dimethyl-formamide

Reference： [1]Lowe III, John A.; Qian, Weimin; Volkmann, Robert A.; Heck, Steven; Nowakowski, Jolanta; Nelson, Robert; Nolan, Charles; Liston, Dane; Ward, Karen; Zorn, Stevin; Johnson, Celeste; Vanase, Michelle; Faraci, W. Stephen; Verdries, Kimberly A.; Baxter, James; Doran, Shawn; Sanders, Martin; Ashton, Mike; Whittle, Peter; Stefaniak, Mark [Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 17, p. 2569 - 2572]

Yield	Reaction Conditions	Operation in experiment
	N-Isobutyl-N'-formylpiperazin If, HCl;
	Piperazin, Isobutylbromid in abs. EtOH;
	entspr. N-Phenylpiperazin, 1) NaNO2/HCl, 2) SO2, Erhitz.;

	1-Ethoxycarbonyl-piperazin, 1.) p-Toluolsulfonsaeure-isobutylester, abs. EtOH, 2.) 20 percentige HCl, Siedetemp.;
	1-Phenyl-4-isobutyl-piperazin, 1. HNO2, 2. wss. KOH;
	(yield)40percent;
		Specific examples of the compounds of the formula (6) are given below. ... 1-ethylpiperazine, 1-propylpiperazine, 1-isopropylpiperazine, 1-butylpiperazine, 1-isobutylpiperazine, 1-sec-butylpiperazine.
		R.6 Synthesis of 1-isobutylpiperazine Reference Example 6 Synthesis of 1-isobutylpiperazine To 1-isobutylpiperazine dihydrochloride (69.5 g) was added 10% aqueous sodium hydroxide solution (100 ml) and then the resulting mixture was extracted with ether. After the extract was concentrated, the residue was distilled under reduced pressure (bp: 172° to 174° C./5 mmHg), thereby yielding 43.7 g of the aimed compound.
		R.29 Synthesis of 4-(2-aminoethyl)-1-isobutylpiperazine To 1-isobutylpiperazine dihydrochloride(69.5 g) was added 10% aqueous solution of sodium hydrochloride(100 ml) and the mixture was extracted with ether. After being concentrated, the extract was distilled under a vacuum(bp 172°-174° C./5 mmHg), thereby yielding 43.7 g of 1-isobutylpiperazine.
	With hydrogenchloride In 1,4-dioxane at 20℃; for 3h;	I.2.2 Step 2. Synthesis of 1- (5- (trifluoromethyl) pyridin-2-yl) piperazine (A-8) General procedure: 1- (5- (trifluoromethyl) pyridin-2-yl) piperazine (13.3 g, 40.0 mmol) was added to 150 mL of a 4N hydrochloric acid-dioxane solution, and the reaction was stirred at room temperature for 3 hours, and the solvent was distilled off under reduced pressure. The residue was adjusted to pH 8-9 with 15% Na2CO3 solution, extracted twice with ethyl acetate, and the organic layers were combined, washed with water and saturated NaCl aqueous solution, and dried with anhydrous Na2SO4 to obtain 8.42 g of A-8, yield 91. %,

15
[ 5308-28-1 ]
[ 102590-21-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; xylene

Reference： [1]Morren et al. [Industrie Chimique Belge, 1957, vol. 22, p. 409,416]

16
[ 5308-28-1 ]
[ 102753-25-3 ]

Yield	Reaction Conditions	Operation in experiment
	With copper; potassium carbonate; xylene

Reference： [1]Hromatka et al. [Monatshefte fur Chemie, 1957, vol. 88, p. 193,196]

17
[ 5308-28-1 ]
[ 1633-82-5 ]
1-(3-chloro-propane-1-sulfonyl)-4-isobutyl-piperazine [ No CAS ]

Reference： [1]Clark, Robin D.; Jahangir, Alam; Alam, Muzaffar; Rocha, Cynthia; Lin, Lin; Bjorner, Bodil; Nguyen, Khanh; Grady, Carole; Williams, Timothy J.; Stepan, George; Tang, Hai Ming; Ford, Anthony P.D.W. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1697 - 1700]

18
6-chloro-N,N'-bis-(3,4-difluoro-phenyl)-[1,3,5]triazine-2,4-diamine [ No CAS ]
[ 5308-28-1 ]
N,N'-bis-(3,4-difluoro-phenyl)-6-(4-isobutyl-piperazin-1-yl)-[1,3,5]triazine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone at 20℃;

Reference： [1]McKay, Geoffrey A.; Reddy, Ranga; Arhin, Francis; Belley, Adam; Lehoux, Dario; Moeck, Greg; Sarmiento, Ingrid; Parr, Thomas R.; Gros, Philippe; Pelletier, Jerry; Far, Adel Rafai [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 5, p. 1286 - 1290]

19
[ 890300-37-5 ]
[ 5308-28-1 ]
3,3'-difluoro-4'-[5-(4-isobutyl-piperazine-1-carbonyl)-pyridin-2-ylamino]-methyl}-biphenyl-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With TEA; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Reference： [1]Kuduk, Scott D.; Di Marco, Christina Ng; Chang, Ronald K.; Wood, Michael R.; Kim, June J.; Schirripa, Kathy M.; Murphy, Kathy L.; Ransom, Richard W.; Tang, Cuyue; Torrent, Maricel; Ha, Sookhee; Prueksaritanont, Thomayant; Pettibone, Douglas J.; Bock, Mark G. [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 10, p. 2791 - 2795]

20
[ 5308-28-1 ]
[ 82044-96-0 ]
(R)-5-[1-(4-Isobutyl-piperazin-1-ylmethyl)-vinyl]-2-methyl-cyclohex-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.4%	With potassium carbonate In ethanol Heating;

Reference： [1]Chen, Jiaojiao; Lu, Min; Jing, Yongkui; Dong, Jinhua [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6539 - 6547]

21
[ 5308-28-1 ]
[ 913701-50-5 ]
C₃₁H₅₆N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40.5%	With triethylamine In N,N-dimethyl-formamide Heating;

Reference： [1]Xu, Liying; Tao, Shujuan; Wang, Xianming; Yu, Zhiying; Wang, Minwei; Chen, Duo; Jing, Yongkui; Dong, Jinhua [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 15, p. 5351 - 5356]

22
[ 5308-28-1 ]
[ 955979-29-0 ]
2-(1H-indol-4-yl)-6-(4-isobutyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide at 20℃;	131 Methanesulfonic acid 2-(lH-indol-4-yl)-4~morpholin~4-yl-thieno[3,2- d]pyrimidin-6-ylmethyl ester, amine and triethylamine were mixed together in DMF and stirred at room temperature. When the reaction was judged to be complete, the solvent was removed under reduced pressure, the residue dissolved in DMSO and purified by preparative HPLC. The chromatographic solvents were removed under reduced pressure to afford the product > 85% purity.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2007/122410, 2007, A1 Location in patent: Page/Page column 136; 138

23
[ 5308-28-1 ]
[ 115023-58-0 ]
C₅₂H₆₆N₄O₁₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide In dimethyl sulfoxide at 20℃;

Reference： [1]Li, Jing; Ma, Zhenkun; Chapo, Katrina; Yan, Dalai; Lynch, A. Simon; Ding, Charles Z. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5510 - 5513]

24
[ 5308-28-1 ]
[ 7483-61-6 ]
C₅₁H₆₄N₄O₁₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide In dimethyl sulfoxide at 20℃;

Reference： [1]Li, Jing; Ma, Zhenkun; Chapo, Katrina; Yan, Dalai; Lynch, A. Simon; Ding, Charles Z. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5510 - 5513]

25
[ 5308-28-1 ]
[ 105396-63-2 ]
[ 129791-92-0 ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide In dimethyl sulfoxide at 20℃;

Reference： [1]Li, Jing; Ma, Zhenkun; Chapo, Katrina; Yan, Dalai; Lynch, A. Simon; Ding, Charles Z. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5510 - 5513]

26
[ 5308-28-1 ]
2,3-dihydrobenzo[1,4]dioxine-5-carboxylic acid{1-[3-(4-isobutylpiperazine-1-sulfonyl)propyl]piperidin-4-ylmethyl}amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: TEA / dimethylformamide / 80 °C

Reference： [1]Clark, Robin D.; Jahangir, Alam; Alam, Muzaffar; Rocha, Cynthia; Lin, Lin; Bjorner, Bodil; Nguyen, Khanh; Grady, Carole; Williams, Timothy J.; Stepan, George; Tang, Hai Ming; Ford, Anthony P.D.W. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1697 - 1700]

27
[ 5308-28-1 ]
O₂₅-Deacetyl-Rifalazil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 53 percent / manganese dioxide / dimethylsulfoxide / 24 h / Ambient temperature 2: 69 percent / sodium hydroxide, water / ethanol / 2 h / Ambient temperature

Reference： [1]Yamane; Hashizume; Yamashita; Konishi; Hosoe; Hidaka; Watanabe; Kawaharada; Yamamoto; Kuze [Chemical and Pharmaceutical Bulletin, 1993, vol. 41, # 1, p. 148 - 155]

28
[ 5308-28-1 ]
2-chloro-5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridine dihydrochloride [ No CAS ]
1-{5-[5-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With cyclohexane; potassium carbonate; potassium iodide In water; xylene	1.B Alternate Example 1B 1-{5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine Alternate Example 1B 1-{5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine. A suspension of 2-chloro-5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridine dihydrochloride (1.07 g, 2.6 mmol), N-isobutylpiperazine (0.95 g, 6.72 mmol), potassium carbonate (0.5 g, 3.62 mmol), and potassium iodide (0.5 g, 0.54 mmol) in xylenes (5 ML) was heated to reflux under a nitrogen atmosphere for 24 hours.. The reaction mixture was then cooled to ambient temperature and a solution of potassium carbonate (19) in water (10 ML) and cyclohexane (10 ML) were added.. The mixture was stirred vigorously for 15 min, and the precipitate was collected by filtration.. The filter cake was washed with water (10 ML) and triturated with methyl tert-butyl ether (4 ML) to provide 1-{5-[5(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine (2.07 mmol). MS m/z 430 (M++1).

Reference： [1]Current Patent Assignee: PFIZER INC - US6355635, 2002, B1 Location in patent: Page column 62

29
[ 629625-93-0 ]
[ 5308-28-1 ]

Yield	Reaction Conditions	Operation in experiment
86.2%	With palladium 10% on activated carbon; hydrogen at 20℃; for 20h;	1-Cyclohexylpyrrolidin-3-amine I-6 General procedure: To a solution of compound I-5 (240 mg) in HFIP (8 mL), 10% Pd/C (120 mg) was added and thenthe reaction mixture was stirred under H2 at room temperature and 1atm for 20 h. Then themixture was filtrated and the filtrate was concentrated to give compound I-6 as yellow oil (100 mg,75%).
	With hydrogen In ethanol at 20℃; for 12h;	2 Benzyl 1-piperazinecarboxylate (1.1 g, 5.00 mmol) and isobutylaldehyde (0.91 mL, 10.0 mmol) were dissolved in 30 mL of tetrahydrofuran, and acetic acid (0.57 mL, 10.0 mmol) and sodium triacetoxyborohydride (2.11 g, 10.0 mmol) were added thereto, and the reaction mixture was stirred at room temperature for two hours. The reaction mixture was mixed with a 1N aqueous solution of sodium hydroxide, extracted with ethyl acetate twice, and the combined organic layers were washed with brine once. The mixture was dried over anhydrous sodium sulfate and evaporated. The resulting residue was purified by silica gel column chromatography (Fuji Silysia, NH Silica gel; ethyl acetate:hexane=50:50) to give benzyl 4-isobutylpiperazin-1-carboxylate (1.05 g) as a colorless oil. The resulting benzyl 4-isobutylpiperazin-1-carboxylate (1.05 g) was dissolved in 35 mL of ethanol, 10% palladium-carbon (750 mg) was added thereto, and the reaction mixture was stirred at room temperature under hydrogen atmosphere (1 atm) for 12 hours. The palladium-carbon was removed by filtration, and the filtrate was evaporated to give the title compound (610 mg) as a colorless oil.1H-NMR Spectrum (CDCl3,400MHz) δ(ppm): 0.90(6H,d,J=6.8Hz), 1.71-1.86(1H,m),2.07(2H,d,J=7.6Hz),2.33-2.43(4H,m),2.86-2.93(4H,m).

Reference： [1]Zhou, Jie; Ji, Ming; Zhu, Zhixiang; Cao, Ran; Chen, Xiaoguang; Xu, Bailing [European Journal of Medicinal Chemistry, 2017, vol. 132, p. 26 - 41]
[2]Current Patent Assignee: EISAI CO LTD - EP1508570, 2005, A1 Location in patent: Page/Page column 134-135

30
[ 5308-28-1 ]
C₅₁H₆₀N₂O₁₄ [ No CAS ]
25-O-deacetyl-25-(2,3-dihydroxypropylcarbonoxy)-21,23-(1-methylethylidene acetal)-5'-[4-isobutyl-1-piperazinyl]benzoxazinorifamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide In dimethyl sulfoxide at 20℃; for 120h;	68 [0444] The general coupling procedure of Example 1 is used to prepare the title compound. To compound 124 (0.20 g) in 3 mL of dimethyl sulfoxide is added 100 mg of 4-isobutylpiperazine and 0.2 g of manganese dioxide. The mixture stirred at room temperature for 5 days. The reaction mixture is diluted by addition of ethyl acetate and insoluble substances are filtered off. The filtrate is washed successively with water and with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. After the drying agent is filtered off, the solvent is removed under reduced pressure. The residue is purified twice by silica-gel column-chromatography [eluent: ethyl acetate/hexane, 1:1 to 9:1 gradient] to give 25-O-deacetyl-25-(2 ,3 -dihydroxypropylcarbonoxy)-21,23-(1-methylethylidene acetal)-5'-[4-isobutyl-1-piperazinyl]benzoxazinorifamycin (compound 125).

Reference： [1]Current Patent Assignee: ACTIVBIOTICS PHARMA - US2005/43298, 2005, A1 Location in patent: Page/Page column 40

31
[ 5308-28-1 ]
2-chloro-5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridine dihydrochloride [ No CAS ]
[ 305379-88-8 ]
1-{5-[5-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; potassium carbonate In cyclohexane; water	A.1.B 1-{5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine. ALTERNATE EXAMPLE 1B 1-{5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine. A suspension of 2-chloro-5-[4-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridine dihydrochloride (1.07 g, 2.6 mmol), N-isobutylpiperazine (0.95 g, 6.72 mmol), potassium carbonate (0.5 g, 3.62 mmol), and potassium iodide (0.5 g, 0.54 mmol) in xylenes (5 mL) was heated to reflux under a nitrogen atmosphere for 24 hours. The reaction mixture was then cooled to ambient temperature and a solution of potassium carbonate (1 g) in water (10 mL) and cyclohexane (10 mL) were added. The mixture was stirred vigorously for 15 min, and the precipitate was collected by filtration. The filter cake was washed with water (10 mL) and triturated with methyl tert-butyl ether (4 mL) to provide 1-{5-[5-(3,4-dichloro-phenyl)-1H-imidazol-2-yl]-pyridin-2-yl}-4-isobutyl-piperazine (2.07 mmol). MS m/z 430 (M++1).

Reference： [1]Current Patent Assignee: PFIZER INC - US2001/39277, 2001, A1

32
1-(isobutyl)-4-(4-nitrophenylpiperazine) [ No CAS ]
1-(isobutyl)-4-(4-nitrophenyl)piperazine [ No CAS ]
[ 5308-28-1 ]
4-[4-(isobutyl)-1-piperazinyl]benzenamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	In ethanol	14.E.B B. B. 4-[4-(isobutyl)-1-piperazinyl]benzenamine A mixture of 1-(isobutyl)-4-(4-nitrophenylpiperazine) (9.4 g, 35.7 mmol) (from Step A above) and 10% palladium-on-charcoal in ethanol (175 mL) was hydrogenated at room temperature at 20 psi for 1.25 hour. The catalyst was filtered off and the filter cake washed thoroughly with ethanol. The mixture was evaporated under reduced pressure to give 4-[4-(isobutyl)-1-piperazinyl] benzenamine (7.8 g, 94%) as a dark red solid.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2002/151554, 2002, A1

33
[ 5308-28-1 ]
[ 120-47-8 ]
[ 405-87-8 ]
[ 459-46-1 ]
1-[4-(4-fluorobenzyloxy)benzoyl]-4-isobutylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		5 1-[4-(4-fluorobenzyloxy)benzoyl]-4-isobutylpiperazine EXAMPLE 5 1-[4-(4-fluorobenzyloxy)benzoyl]-4-isobutylpiperazine It was synthesised in the manner identical to Example 3. Namely, ethyl 4-hydroxybenzoate (2.50 g) was benzylated with 4-fluorobenzyl bromide (2.84 g) and then hydrolyzed. From thus obtained 3.57 g of 4-(4-fluorobenzyloxy) benzoic acid, 1.24 g was subjected to a condensation reaction with 1-isobutylpiperazine (0.71 g), thereby yielding 1.08 g of the aimed compound. mp 109.0°-110.2° C.; 1 H-NMR (CDCl3)δ: 7.41(2H, d, J=8.8 Hz), 7.38(2H, d, J=8.8Hz), 7.08(2H, t, J=8.8 Hz), 6.96(2H, d, J=8.8 Hz), 5.05(2H, s), 3.85-3.35(4H, m), 2.50-2.25(4H, m), 2.10(2H, d, J=7.3 Hz), 1.88-1.71(1H, m), 0.90(6H, d, J=6.8 Hz).

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5756505, 1998, A

34
[ 5308-28-1 ]
[ 4489-46-7 ]
[ 590-17-0 ]
[ 4649-58-5 ]

Yield	Reaction Conditions	Operation in experiment
		R.29 Synthesis of 4-(2-aminoethyl)-1-isobutylpiperazine By using 1-isobutylpiperazine (2.84 g) and bromoacetonitrile(2.40 g), as in the case of Reference Example 28, 1.19 g (15%) of 4-(2-aminoethyl)-1-isobutylpiperazine was obtained.

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5814634, 1998, A

35
[ 5308-28-1 ]
[ 182677-43-6 ]
[ 1499-21-4 ]
1-[4-(4-fluorobenzyloxy)-3-isobutylbenzoyl]-4-isobutylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In hexane; chloroform; triethylamine	21 1-[4-(4-fluorobenzyloxy)-3-isobutylbenzoyl]-4-isobutylpiperazine EXAMPLE 21 1-[4-(4-fluorobenzyloxy)-3-isobutylbenzoyl]-4-isobutylpiperazine 4-(4-fluorobenzyloxy)-3-isobutylbenzoic acid (16.5 g) was dissolved in a mixture of chloroform (150 ml) and triethylamine (15.3 ml). To this mixture was added diphenylphosphinic chloride (11.5 ml) while being cooled with ice. After being stirred for 40 minutes, the mixture, with 1-isobutylpiperazine (7.83 g) added thereto, was stirred for 1.5 hours at room temperature. This reaction mixture was washed with saturated sodium hydrogencarbonate solution and saturated brine successively, dried over sodium sulfate anhydride, and then concentrated under a vacuum. Thus obtained residue was purified by silica gel column chromatography (chloroform: methanol=50:1) and the resulting solid was recrystallized (from n-hexane), thereby yielding 19.6 g of the aimed compound. mp 77.0°-78.0° C.; 1 H-NMR (CDCl3)δ: 7.39(2H, dd, J=8.8,5.4 Hz), 7.25(1H, d, J=8.8 Hz), 7.17(1H, s), 7.08(2H, t, J=8.8 Hz), 6.87(1H, d, J=8.8 Hz), 5.05(2H, s), 3.90-3.35(4H, m), 2.53(2H, d, J=6.8 Hz), 2.55-2.25(4H, m), 2.10(2H, d, J=7.3 Hz), 2.01-1.91(1H, m), 1.88-1.71(1H, m), 0.90(6H, d, J=6.4 Hz), 0.89(6H, d, J=6.8 Hz).

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5756505, 1998, A

36
[ 5308-28-1 ]
4-(4-fluorobenzyloxy)-3-methallylbenzoic acid [ No CAS ]
1-[4(4-fluorobenzyloxy)-3-methallylbenzoyl]-4-isobutylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		4 1-[4-(4-fluorobenzyloxy)-3-methallylbenzoyl]-4-isobutylpiperazine hydrochloride As in the case of Example 16, this compound (2.13 g) was subjected to a condensation reaction with 1-isobutylpiperazine (1.01 g), thereby yielding 1-[4(4-fluorobenzyloxy)-3-methallylbenzoyl]-4-isobutylpiperazine.

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5756505, 1998, A

37
[ 5308-28-1 ]
[ 182677-42-5 ]
[ 1499-21-4 ]
1-(4-benzyloxy-3-isobutylbenzoyl)-4-isobutylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform; triethylamine	16 1-(4-benzyloxy-3-isobutylbenzoyl)-4-isobutylpiperazine EXAMPLE 16 1-(4-benzyloxy-3-isobutylbenzoyl)-4-isobutylpiperazine 4-benzyloxy-3-isobutylbenzoic acid (4.94 g) was dissolved in a mixture of chloroform (60 ml) and triethylamine (4.83 ml). To this mixture, diphenylphosphinic chloride (3.66 ml) was added while being cooled with ice. After being stirred for 40 minutes, the mixture, with 1-isobutylpiperazine (2.48 g) added thereto, was stirred for 1.5 hours at room temperature. The reaction mixture was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine successively, dried over sodium sulfate anhydride, and then concentrated under a vacuum. Thus obtained residue was purified by silica gel column chromatography (chloroform: methanol=50:1), thereby yielding 7.11 g of the aimed compound. 1 H-NMR (CDCl3)δ: 7.44-7.37(4H, m), 7.33(1H, d, J=8.8 Hz), 7.26-7.23(1H, m), 7.17(1H, s), 6.89(1H, d, J=8.8 Hz), 5.10(2H, s), 3.90-3.35(4H, m), 2.55(2H, d, J=7.3 Hz), 2.55-2.25(4H, m), 2.10(2H, d, J=7.3 Hz), 2.01-1.91(1H, m), 1.88-1.71(1H, m), 0.91(6H, d, J=6.8 Hz), 0.90(6H, d, J=6.8 Hz).

Reference： [1]Current Patent Assignee: SHISEIDO COMPANY LIMITED - US5756505, 1998, A

38
[ 5308-28-1 ]
[ 84468-15-5 ]
1-(5-isoquinolinesulfonyl)-4-isobutylpiperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide; potassium carbonate In chloroform methanol; chloroform	9 EXAMPLE 9 EXAMPLE 9 In 30 ml of chloroform were added 1.42 g of 1-isobutylpiperazine and 2.76 g of potassium carbonate, and to the mixture was added dropwise 50 ml of a chloroform solution containing 2.28 g of 5-isoquinolinesulfonyl chloride under cooling with ice. After the dropwise addition of the chloroform solution, the mixed solution thus obtained was stirred at a temperature of 15° C. to 25° C. for two hours, and then the reaction solution was washed with 20 ml of a 1N aqueous sodium hydroxide solution and extracted twice with a 5N aqueous hydrochloric acid solution. The aqueous hydrochloric acid layer was rendered alkaline, extracted three time with 30 ml of chloroform, and the chloroform layer extracted was washed with water and dried with anhydrous magnesium sulfate. After the chloroform was distilled therefrom under reduced pressure, the residue obtained was subjected to a silica gel column chromatography (silica gel: 100 g; solvent: 2% methanol-chloroform) to give 2.60 g of 1-(5-isoquinolinesulfonyl)-4-isobutylpiperazine, i.e., Compound (47) in a yield of 78%. Melting point (the dihydrochloride recrystallized from ethanol): 234° C. Mass spectrum (m/e): 333(M+), 290(M-C3 H7), 141 and 128 NMR spectrum (CDCl3, δ): 0.8(6H, d, 2CH3), 1.2-2.0(1H, m, CH), 2.0-3.3(10H, 5NCH2), 7.6-8.8(5H) and 9.3(1H, s) IR absorption spectrum (νmax,cap cm-1): 3430, 1620, 1350, 1340, 1170 and 1145.

Reference： [1]Current Patent Assignee: HIDAKA; ASAHI KASEI CORPORATION - US4456757, 1984, A

39
[ 5308-28-1 ]
[ 77776-75-1 ]
[ 77777-04-9 ]

Yield	Reaction Conditions	Operation in experiment
		49 8-Benzylthio-2-(N-isobutyl-piperazino)-4-morpholino-pyrimido-[5,4-d]-pyrimidine Example 49 8-Benzylthio-2-(N-isobutyl-piperazino)-4-morpholino-pyrimido-[5,4-d]-pyrimidine This compound was prepared analogous to Example 1 from 8-benzylthio-2-chloro-4-morpholino-pyrimido-[5,4-d]-pyrimidine (m.p.: 159°-161° C.) and N-isobutyl-piperazine. M.p.: 152°-155° C. (ethyl acetate).

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US4518596, 1985, A

40
[ 5308-28-1 ]
[ 2942-59-8 ]
[ 1159850-92-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-ethyl-N,N-diisopropylamine In water at 200℃; for 2h; Microwave irradiation; Biotage Initiator;

Reference： [1]Location in patent: experimental part Quevedo, Camilo E.; Bavetsias, Vassilios; McDonald, Edward [Tetrahedron Letters, 2009, vol. 50, # 21, p. 2481 - 2483]

41
[ 5308-28-1 ]
[ 662116-67-8 ]
[ 942948-54-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 45℃; for 18h;	36 5-Chloro-4-(4-isobutylpiperazin-1-yl)-3-nitropyridin-2-amine To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.060 g, 0.29 mmol) and isopropanol (4.5 ml) was added 1-isobutyl-piperazine (0.045 g, 0.32 mmol) with the aid of isopropanol (0.5 ml) followed by diisopropylethylamine (0.06 ml, 0.32 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature, and concentrated in vacuo. The residue was absorbed on silica gel, the free running powder was placed on a 10 g isolute silica column which was eluted with ethyl acetate/dichloromethane (v/v; 1:1). The title compound was obtained as an orange solid (0.054 g, 60%); 1H-NMR (500 MHz, DMSO-d6) 0.87 (d, J=6.57 Hz, 6H, CH(CH3)2), 1.77 (m, 1H, CH(CH3)2), 2.08 (d, J=7.39 Hz, 2H, N-CH2), 2.45 (br s, 4H, piperazine N(CH2)2), 3.05 (br s, 4H, piperazine N(CH2)2), 6.94 (s, 2H, NH2), 8.06 (s, 1H, 6-H);LC (Method B)-MS (ESI, m/z): Rt=1.70 min-314, 316 [(M+H)+, Cl isotopic pattern].

Reference： [1]Current Patent Assignee: UNIVERSITY OF LONDON - US2009/247507, 2009, A1 Location in patent: Page/Page column 27

42
[ 5308-28-1 ]
[ 942947-95-7 ]
[ 942948-47-2 ]

Yield	Reaction Conditions	Operation in experiment
63%	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 45℃; for 20h;	To a mixture of <strong>[942947-95-7]5-bromo-4-chloro-3-nitro-pyridin-2-ylamine</strong> (0.126 g, 0.50 mmol) and isopropanol (9 ml) was added 1-isobutylpiperazine (0.078 g, 0.55 mmol) with the aid of isopropanol (5 ml) followed by diisopropylethylamine (0.10 ml, 0.57 mmol). The reaction mixture was heated at 45 C. for 20 h, then allowed to cool to room temperature. The precipitate was collected by filtration and washed with isopropanol and diethyl ether. The title compound was thus obtained as a yellow solid (0.112 g, 63%). 1H-NMR (500 MHz, DMSO-d6) 0.87 (d, J=6.56 Hz, 6H, CH(CH3)2), 1.77 (m, 1H, CH(CH3)2), 2.08 (d, J=7.35 Hz, 2H, N-CH2), 2.47 (br s, 4H, piperazine N(CH2)2), 3.04 (br s, 4H, piperazine N(CH2)2), 6.96 (s, 2H, NH2), 8.15 (s, 1H, 6-H);LC (Method B)-MS (ESI, m/z): Rt=1.80 min-358, 360 [(M+H)+, Br isotopic pattern].

Reference： [1]Patent: US2009/247507,2009,A1 .Location in patent: Page/Page column 25
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 5213 - 5228

43
[ 5308-28-1 ]
[ 27514-08-5 ]
[ 1214265-89-0 ]

Yield	Reaction Conditions	Operation in experiment
54%		Preparation 16: 4-(4-i-Butylpiperazin-l-yl)cyclohexanamine (cis and trans isomers); [0126] In a 250 mL flask, <strong>[27514-08-5]4-acetamidocyclohexanone</strong> (5.47 g, 35.2 mmol), N-i-butyl piperazine (10 g, 70.3 mmol) were dissolved in dry toluene (75 mL) and added methanesulfonic acid (MSA) (250 muL) and refluxed using Dean-Stark apparatus for five hours with occasional decanting toluene from Dean-Stark apparatus 3-4 times. Then removed half of the toluene from the apparatus and cooled to 500C and added 75 mL ethanol then removed the Dean-Stark apparatus and cooled to 15-200C. Added NaBH4 (35.2 mmol) portion wise under nitrogen atmosphere. Continued stirring the reaction for overnight. Then added NaBH4 (50 mmols), after 30 min added 12 rnL of 4 N HCl drop wise to the reaction. The volatiles were removed from the reaction under reduced pressure. Basified the gummy solid reaction mixture with 12 mL sat.K^CCh, diluted with another 12 mL water and further basified with 50% NaOH solution to pH about 13. Then added EtOAc (100 mL) and filtered the solid product and washed with EtOAc and ether and collected N-(4-(4-i-burtylpiperazin-l-yl)cyclohexyl)acetamide (cis and trans isomers) as white powder (5.3 g, 54%). ESI-MS: m/z 282 (M+H)+. N-(4-(4-propylpiperazin-l- yl)cyclohexyl)acetamide (5.2 g, 18.5 mmol) was refluxed in 24% cone. HCl solution for 20 hours at 115C. Then evaporated the solution under reduced pressure and the solid product obtained was dissolved and recrystallized from isopropyl alcohol to get the product as white hydrochloride salt (5.2 g). ESI-MS: m/z 240 (M+H) +.

Reference： [1]Patent: WO2010/25073,2010,A1 .Location in patent: Page/Page column 28-29

44
[ 5308-28-1 ]
[ 959771-66-5 ]
C₂₃H₂₅Cl₂FN₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide

Reference： [1]Location in patent: scheme or table Pescatore, Giovanna; Branca, Danila; Fiore, Fabrizio; Kinzel, Olaf; Bufi, Laura Llauger; Muraglia, Ester; Orvieto, Federica; Rowley, Michael; Toniatti, Carlo; Torrisi, Caterina; Jones, Philip [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 3, p. 1094 - 1099]

45
[ 5308-28-1 ]
C₂₁H₃₀O₈ [ No CAS ]
2-(dispiro[cyclohexane-1,3'-[1,2,4,5]tetroxane-6',2''-tricyclo[3.3.1.1(3,7)]decan]-4-yl)-1-(4-isobutylpiperazin-1-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 0 - 20℃;

Reference： [1]O'Neill, Paul M.; Amewu, Richard K.; Nixon, Gemma L.; ElGarah, Fatima Bousejra; Mungthin, Mathirut; Chadwick, James; Shone, Alison E.; Vivas, Livia; Lander, Hollie; Barton, Victoria; Muangnoicharoen, Sant; Bray, Patrick G.; Davies, Jill; Park, B. Kevin; Wittlin, Sergio; Brun, Reto; Preschel, Michael; Zhang, Kesheng; Ward, Stephen A. [Angewandte Chemie - International Edition, 2010, vol. 49, # 33, p. 5693 - 5697]

46
[ 5308-28-1 ]
[ 1257437-09-4 ]
[ 1257432-85-1 ]

Yield	Reaction Conditions	Operation in experiment
58%	In tert-Amyl alcohol at 110℃; for 4h;	1 Example 1 : i-^-Fluoro-benzenesulfonyO-pyrrolidine^S-carboxylic acid [2-(4- isobutyl-piperazin-1-yl)-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-ylmethyl]- amide.; To a solution of 1-(4-fluoro-benzenesulfonyl)-pyrrolidine-2S-carboxylic acid [2-phenylmethanesulfonyl-6-(4-trifluoromethyl-phenyl)-pyrimidin-4- ylmethyl]-amide (0.65 g, 0.982 mmol) in f-amyl alcohol (10 mL) was added isobutylpiperazine (0.42 g, 2.95 mmol). The resulting mixture was heated to 110 0C for 4 hours then allowed to cool to rt. The resulting mixture was concentrated and purified by preparative reverse-phase HPLC to afford the title compound as a colorless solid (0.37 g, 58%). MS (ESI): mass calcd. for C3IH36F4N6O3S, 648.2; m/z found, 649.5 [M+H]+. 1H NMR (CDCI3) δ 8.17 (d, J = 8.33 Hz, 2H), 8.07 (t, J = 4.76, 4.76 Hz, 1 H), 7.93-7.88 (m, 2H), 7.72-7.68 (m, 1 H), 7.28-7.22 (m, 2H), 6.95 (s, 1 H), 4.59 (dd, J = 17.56, 5.19 Hz, 1 H), 4.42 (dd, J = 17.56, 4.80 Hz, 1 H), 4.18 (dd, J = 8.79, 2.39 Hz, 1 H), 4.03-3.96 (m, 4H), 3.67-3.57 (m, 1 H), 3.25-3.15 (m, 1 H), 2.57-2.45 (m, 4H), 2.30-2.22 (m, 1 H), 2.14 (d, J = 7.32 Hz, 2H), 1.91-1.75 (m, 2H), 1.74-1.51 (m, 3H), 0.94 (d, J = 6.57 Hz, 6H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2010/141805, 2010, A1 Location in patent: Page/Page column 70

47
[ 5308-28-1 ]
[ 951135-51-6 ]
[ 1260242-68-9 ]

Yield	Reaction Conditions	Operation in experiment
	In tert-Amyl alcohol at 120℃;

Reference： [1]Location in patent: scheme or table Lebsack, Alec D.; Rech, Jason C.; Branstetter, Bryan J.; Hawryluk, Natalie A.; Merit, Jeffrey E.; Allison, Brett; Rynberg, Raymond; Buma, Johnathan; Rizzolio, Michele; Swanson, Nadia; Ao, Hong; Maher, Michael P.; Herrmann, Michelle; Freedman, Jamie; Scott, Brian P.; Luo, Lin; Bhattacharya, Anindya; Wang, Qi; Chaplan, Sandra R.; Wickenden, Alan D.; Breitenbucher, J. Guy [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 23, p. 7142 - 7146]

48
[ 5308-28-1 ]
OZ-78 [ No CAS ]
C₂₆H₄₂N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: OZ-78 With triethylamine; methyl chloroformate In dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: 1-isobutylpiperazine In dichloromethane at 0 - 20℃; for 2.75h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Bousejra-El Garah, Fatima; Wong, Michael He-Long; Amewu, Richard K.; Muangnoicharoen, Sant; Maggs, James L.; Stigliani, Jean-Luc; Park, B. Kevin; Chadwick, James; Ward, Stephen A.; O'Neill, Paul M. [Journal of Medicinal Chemistry, 2011, vol. 54, # 19, p. 6443 - 6455]

49
[ 5308-28-1 ]
[ 1245318-94-8 ]
[ 1245319-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 70℃; for 6h;	190 To a solution of 5-amino-7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine X (50 mg, 0.19 mmol) in dioxane (5 ml) was added diisopropylethylamine (0.28 mmol, 47 μL) and a piperazine derivative (0.28 mmol). The reaction was stirred at 70° C. for 6 hours after which the solvent was removed in vacuo. The resulting residue was purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio gradually ranging from 100% CH2Cl2 to 2% CH3OH in CH2Cl2), yielding the pure title compounds which were characterized by their mass spectra as indicated below:The following compounds were synthesized according to this procedure:Example 190 Synthesis of 5-amino-2-(4-fluorophenyl)-7-(4-isobutylpiperazin-1-yl)-oxazolo[5,4-d]pyrimidineThis compound was obtained from 1-isobutyl-piperazine (32 mg);MS m/z (%): 371 ([M+H]+, 100).
32 mg	With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 70℃; for 6h;	190 Example 190 Synthesis of 5-amino-2-(4-fluorophenyl)-7-(4-isobutylpiperazin-1-yl)-oxazolo[5,4-d]pyrimidine Examples 190-192 Synthesis of 5-amino-2-(4-fluorophenyl)-7-piperazin-1-yl-oxazolo[5,4-d]pyrimidine analogues General Procedure [0979] To a solution of 5-amino-7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine X (50 mg, 0.19 mmol) in dioxane (5 ml) was added diisopropylethylamine (0.28 mmol, 47 μL) and a piperazine derivative (0.28 mmol). The reaction was stirred at 70° C. for 6 hours after which the solvent was removed in vacuo. The resulting residue was purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio gradually ranging from 100% CH2Cl2 to 2% CH3OH in CH2Cl2), yielding the pure title compounds which were characterized by their mass spectra as indicated below: [0980] The following compounds were synthesized according to this procedure: Example 190 Synthesis of 5-amino-2-(4-fluorophenyl)-7-(4-isobutylpiperazin-1-yl)-oxazolo[5,4-d]pyrimidine This compound was obtained from 1-isobutyl-piperazine (32 mg); MS m/z (%): 371 ([M+H]+, 100).
32 mg	With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 70℃; for 6h;	190 Synthesis of 5-amino-2-(4-fluorophenyl)-7-(4-isobutylpiperazin-1-yl)-oxazolo[5,4-d]pyrimidine To a solution of 5-amino-7-chloro-2-(4-fluorophenyl)-oxazolo[5,4-d]pyrimidine X (50 mg, 0.19 mmol) in dioxane (5 ml) was added diisopropylethylamine (0.28 mmol, 47 μL) and a piperazine derivative (0.28 mmol). The reaction was stirred at 70° C. for 6 hours after which the solvent was removed in vacuo. The resulting residue was purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio gradually ranging from 100% CH2Cl2 to 2% CH3OH in CH2Cl2), yielding the pure title compounds which were characterized by their mass spectra as indicated below: [0996] The following compounds were synthesized according to this procedure: Example 190 Synthesis of 5-amino-2-(4-fluorophenyl)-7-(4-isobutylpiperazin-1-yl)-oxazolo[5,4-d]pyrimidine [0997] This compound was obtained from 1-isobutyl-piperazine (32 mg); [0998] MS m/z (%): 371 ([M+H]+, 100).

Reference： [1]Current Patent Assignee: KATHOLIEKE UNIVERSITEIT LEUVEN - US2012/46278, 2012, A1 Location in patent: Page/Page column 67
[2]Current Patent Assignee: KATHOLIEKE UNIVERSITEIT LEUVEN - US2013/190297, 2013, A1 Location in patent: Paragraph 0979; 0980; 0981; 0982
[3]Current Patent Assignee: KATHOLIEKE UNIVERSITEIT LEUVEN - US2014/88088, 2014, A1 Location in patent: Paragraph 0995-0998

50
[ 5308-28-1 ]
[ 1372616-37-9 ]
[ 1442655-83-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With manganese(IV) oxide In dimethyl sulfoxide at 20℃; for 24h;	RLZ analog (2e). A mixture of benzoxazinorifamycin 2d (5.5 mg, 0.005 mmol), l-(2- methylpropy piperazine (2.3 mg, 0.016 mmol; Oakwood Products Inc.), Mn02 (5 mg, 0.055 mmol) and DMSO (0.5 mL) was stirred at room temperature for 24 h and then filtered over Celite. The filtrate was concentrated and purified by preparative TLC, eluting with dichloromethane : methanol (90 : 10). The product band was processed to give 2e (4.6 mg, 74%) as a dark blue solid: HPLC 5.33 min (95.3% purity); MS (ES+) m/z 1189.5 (M+H)+; HRMS (MALDI) calcd for C49H61N3O13 [(M + H)+], 1189.6180; found 1189.6193.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - WO2013/86415, 2013, A1 Location in patent: Page/Page column 42

51
[ 5308-28-1 ]
[ 1509924-99-5 ]
[ 1509925-23-8 ]

Yield	Reaction Conditions	Operation in experiment
47%	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 In N,N-dimethyl-formamide at 20℃; for 3h;

Reference： [1]Keenan, Martine; Chaplin, Jason H.; Alexander, Paul W.; Abbott, Michael J.; Best, Wayne M.; Khong, Andrea; Botero, Adriana; Perez, Catherine; Cornwall, Scott; Thompson, R. Andrew; White, Karen L.; Shackleford, David M.; Koltun, Maria; Chiu, Francis C. K.; Morizzi, Julia; Ryan, Eileen; Campbell, Michael; Von Geldern, Thomas W.; Scandale, Ivan; Chatelain, Eric; Charman, Susan A. [Journal of Medicinal Chemistry, 2013, vol. 56, # 24, p. 10158 - 10170]

52
[ 5308-28-1 ]
[ 1610379-38-8 ]
[ 1610379-05-9 ]

Yield	Reaction Conditions	Operation in experiment
34%	With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 6h;	5 2-(6-(4-Isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one Example 5 2-(6-(4-Isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one To a suspension of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.108 g, 0.36 mmol) in N,N-dimethylformamide (1.5 mL) was added K2CO3 (0.15 g, 1.07 mmol) and 1-isobutyl-piperazine (88.94, 0.54 mmol). The resulting mixture was heated at 110° C. for 6 h. After that time N,N-dimethylacetamide (1.5 mL) was added and heating was continued for 20 h. After that time the reaction mixture was cooled to rt, diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with water, and dried under high vacuum. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol) to give 2-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.052 g, 34%) as a yellow solid: mp 188-189° C.; 1H NMR (400 MHz, CDCl3) δ 10.33 (br s, 1H), 7.83 (d, J=7.42 Hz, 1H), 7.65 (dd, J=8.59, 7.42, 1H), 6.76-6.88 (m, 2H), 6.48 (d, J=2.34 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.64 (t, J=4.88 Hz, 4H), 2.55 (t, J=4.88 Hz, 4H), 2.17 (d, J=7.42 Hz, 2H), 1.75-1.95 (m, 1H), 0.95 (d, J=6.64 Hz, 6H); ESI MS m/z 424 [M+H]+.

Reference： [1]Current Patent Assignee: ZENITH CAPITAL CORP - US2014/142102, 2014, A1 Location in patent: Paragraph 0522; 0523

53
[ 5308-28-1 ]
1-(3-(dimethylamino)propyl)-1H-indole-5-carboxylic acid [ No CAS ]
(1-(3-(dimethylamino)propyl)-1H-indol-5-yl)(4-isobutylpiperazin-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 40℃;	Preparation of Compound 4022, (1-{3-{dimethylammo)propyl}-1/f ndol-'5-yl}{4- tofoutylpiperazin-1-yl)methanone Preparation of Compound 4022, (1-{3-{dimethylammo)propyl}-1/f ndol-'5-yl}{4- tofoutylpiperazin-1-yl)methanone To a solution of 1-(3-(dimethy}arnino)propyl)-1 H-indole-5-carboxylic acid (246 mg, 10 mmol) and 1 -isobutylpiperazine (142 mg, 1.0 mmol) in DMF (10 mL) was added EDCI (384 mg, 2.0 mmol). The mixture was stirred at 40 °C overnight. The reaction mixture was then partitioned between EtOAc and water. The organic layer was washed with water and brine, then dried, concentrated and purified by rep-TLC (MeOH/DCM=1/20) to afford the target product (48 mg, 13%). 1H NMR (400 MHz, CDCI3): 6 7.71 (br s, 1H), 7.38 (d, J - 8.8 Hz, 1 H), 7.29 (del, J ~ 8.4 Hz, 1.2 Hz, 1 H), 7.18 (d, J = 3.2 Hz, 1H), 6.53 (d, J = 3.2 Hz, 1 H), 4.22 (t J = 7.2 Hz, 2H), 3.66 (br s, 4H), 2.42 (br s, 4H), 2.28-2.25 (m, 8H), 2.12 (d, J = 7.6 Hz, 2H), 2.00 (quintet, J ~ 7,6 Hz, 2H), 1.80-170 (m, 1 H), 0.92 (d, J ~ 6,4 Hz, 6H), LC S: m/z 371.3 [M+H3+,

Reference： [1]Current Patent Assignee: NOVOGEN LTD - WO2015/74123, 2015, A1 Location in patent: Page/Page column 55

54
[ 5308-28-1 ]
{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid [ No CAS ]
N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(2-methylpropyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile at 80℃; for 2h;	317 N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(2-methylpropyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide 2-(Methylsulfanyl)ethan-1-amine (0.5 mL, 5.34 mmol) was added to a solution of N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (120 mg, 0.23 mmol) in CH3CN (3 mL). The resulting solution was stirred at 80° C. for 2 h and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 10 mmol NH4HCO3 and MeCN (40.0% up to 57.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 40.0% in 2 min); Detector, UV 254/220 nm. This resulted in 58.2 mg (48%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[[2-(methylsulfanyl)ethyl]-amino]ethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a yellow solid. LCMS (Method 20) [M+H]+=522.2, RT=2.50 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.34 (dd, 1H, J=1.6, 6.8 Hz), 8.67 (dd, 1H, J=1.6, 4.4 Hz), 8.67 (s, 1H), 8.36 (s, 1H), 7.68-7.61 (m, 2H), 7.46-7.44 (m, 1H), 7.28 (dd, 1H, J=4.4, 7.2 Hz), 7.06 (t, 1H, J=73.2 Hz), 4.23 (t, 2H, J=6.4 Hz), 2.98 (t, 2H, J=6.0 Hz), 2.71 (t, 2H, J=6.8 Hz), 2.53 (t, 2H, J=6.8 Hz), 2.03 (s, 3H). Using synthetic method analoguous to that of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(1-phenylethyl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide, the title compound was prepared from {3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid and 1-(2-methylpropyl)piperazine. LCMS (Method 25) [M+H]+=587.1, RT=1.80 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.33 (dd, 1H, J=1.8, 6.9 Hz), 8.68 (dd, 1H, J=1.5, 3.9 Hz), 8.67 (s, 1H), 8.31 (s, 1H), 7.62 (dd, 1H, J=3.0, 8.7 Hz), 7.55 (d, 1H, J=2.7 Hz), 7.45 (d, 1H, J=9.0 Hz), 7.28 (dd, 1H, J=4.2, 7.2 Hz), 7.02 (t, 1H, J=73.2 Hz), 5.23 (s, 2H), 3.57-3.42 (m, 4H), 2.40-2.21 (m, 4H), 2.05 (d, 2H, J=7.2 Hz), 1.81-1.76 (m, 1H), 0.86 (d, 6H, J=6.3 Hz).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2015/336962, 2015, A1 Location in patent: Paragraph 0737; 0748; 0749

55
[ 5308-28-1 ]
2-bromo-N-[1-(1H-indol-3-yl)hexan-2-yl]-1,3-thiazole-5-carboxamide [ No CAS ]
N-(1-(1H-indol-3-yl)hexan-2-yl)-2-(4-isobutylpiperazin-1-yl)thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium carbonate In acetonitrile at 80℃; for 16h;	5 Example 5: N-(l-(lH-Indol-3-yl)hexan-2-yl)-2-(4-isobutylpiperazin-l-yl)thiazole-5- carboxamide. To a solution of N-(l-(lH-indol-3-yl)hexan-2-yl)-2-bromothiazole-5- carboxamide (0.20 g, 0.49 mmol) and 1-isobutylpiperazine (0.05 g, 0.54 mmol) in CH3CN (4.5 mL) was added K2C03 (0.20 g, 1.47 mmol) and the reaction mixture was heated at 80 °C for 16 h. The reaction mixture was concentrated in vacuo. The residue was diluted with H20 (10 mL) and extracted with 10% MeOH in DCM (10 mL). The organic layer was separated, dried over anhydrous Na2S04 and concentrated in vacuo. The crude obtained was purified by column chromatography (silica 230-400 mesh, 0 to 10% MeOH in DCM) and then triturating with petroleum ether (6 mL), pentane (10 mL) and DCM (2 mL) to afford N-(l-(lH-indol-3- yl)hexan-2-yl)-2-(4-isobutylpiperazin-l-yl)thiazole-5-carboxamide (0.16 g, 69%) as an off-white solid. HPLC Purity: 97.4%. LC/MS (ESI) m/e [M+H]+/RT (min)/%: 468.00/3.33/99.52%. 1H NMR (400 MHz, DMSO- 6) δ 0.81 (t, = 6.8 Hz, 3H), 0.87 (d, = 6.4 Hz, 6H), 1.13-1.37 (m, 4H), 1.42-1.58 (m, 2H), 1.76-1.82 (m, 1H), 2.08 (d, = 6.8 Hz, 2H), 2.40-2.48 (m, 4H), 2.73- 2.95 (m, 2H), 3.42-3.48 (m, 4H), 4.10-4.18 (m, 1H), 6.92-6.99 (m, 1H), 7.04 (t, J = 7.3 Hz, 1H), 7.09 (brs, 1H), 7.31 (d, / = 8.3 Hz, 1H), 7.57 (d, = 7.3 Hz, 1H), 7.80 (s, 1H), 7.94 (d, = 8.8 Hz, 1H), 10.75 (brs, 1H).

Reference： [1]Current Patent Assignee: UCB - WO2017/20010, 2017, A1 Location in patent: Paragraph 0115

56
[ 5308-28-1 ]
2-carboxyl-1H-benzo[d]immidazole-4-carboxamide [ No CAS ]
2-(4-iso-butylpiperazine-1-carbonyl)-1H-benzo[d]imidazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18.7%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 20h;	6.2.1. tert-Butyl 3-(4-carbamoyl-1H-benzo[d]imidazole-2-carboxamido)pyrrolidine-1-carboxylate (7a) General procedure: A mixture of 2-carboxyl-1H-benzo[d]immidazole-4-carboxamide (75 mg, 0.37 mmol), EDC (210 mg, 1.09 mmol), HOBt(147 mg, 1.09 mmol), Et3N (0.4 mL, 2.93 mmol) and N-Boc-aminopyrrolidine(202 mg, 1.09 mmol) in DMF (5 mL) was stirred atroom temperature for 20 h and then H2O was added to the mixture.The solutionwas extracted with the solvent mixture (ethyl acetate/methanol = 10:1) (30 mL x 3) and then the organic layer waswashed with brine (20 mL x 2). The combined organic layer wasdried over anhydrous MgSO4. After filtration and concentration, thecrude product was obtained and purified with column chromatography(methylene chloride/methanol 50:1 to 40:1) to givecompound 7a as a white solid (74 mg, 54.4%).

Reference： [1]Zhou, Jie; Ji, Ming; Zhu, Zhixiang; Cao, Ran; Chen, Xiaoguang; Xu, Bailing [European Journal of Medicinal Chemistry, 2017, vol. 132, p. 26 - 41]

57
[ 5308-28-1 ]
[ 66630-70-4 ]
(4-isobutylpiperazin-1-yl)(2-phenyl-1H-benzo[d]imidazol-5-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.022 g	Stage #1: 2-phenyl-1H-benzo[d]imidazole-6-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 1-isobutylpiperazine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18h;

Reference： [1]Periasamy, Jayaprakash; Kurdekar, Vadiraj; Jasti, Subbarao; Nijaguna, Mamatha B.; Boggaram, Sanjana; Hurakadli, Manjunath A.; Raina, Dhruv; Kurup, Lokavya Meenakshi; Chintha, Chetan; Manjunath, Kavyashree; Goyal, Aneesh; Sadasivam, Gayathri; Bharatham, Kavitha; Padigaru, Muralidhara; Potluri, Vijay; Venkitaraman, Ashok R. [Cell Chemical Biology, 2018, vol. 25, # 6, p. 677 - 12,690]

58
[ 5308-28-1 ]
[ 1156513-54-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 36 h / 60 °C 2: acetic acid; palladium on activated charcoal; hydrogen / methanol / 4 h / 25 °C

Reference： [1]Le Manach, Claire; Paquet, Tanya; Wicht, Kathryn; Nchinda, Aloysius T.; Brunschwig, Christel; Njoroge, Mathew; Gibhard, Liezl; Taylor, Dale; Lawrence, Nina; Wittlin, Sergio; Eyermann, Charles J.; Basarab, Gregory S.; Duffy, James; Fish, Paul V.; Street, Leslie J.; Chibale, Kelly [Journal of Medicinal Chemistry, 2018, vol. 61, # 20, p. 9371 - 9385]

59
[ 5308-28-1 ]
2-(4,4-difluorocyclohexyl)-N-(5-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-6-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 36 h / 60 °C 2: acetic acid; palladium on activated charcoal; hydrogen / methanol / 4 h / 25 °C 3: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine / <i>tert</i>-butyl alcohol; toluene / 110 °C / Inert atmosphere 4: trifluoroacetic acid / neat (no solvent) / 12 h / 100 °C

Reference： [1]Le Manach, Claire; Paquet, Tanya; Wicht, Kathryn; Nchinda, Aloysius T.; Brunschwig, Christel; Njoroge, Mathew; Gibhard, Liezl; Taylor, Dale; Lawrence, Nina; Wittlin, Sergio; Eyermann, Charles J.; Basarab, Gregory S.; Duffy, James; Fish, Paul V.; Street, Leslie J.; Chibale, Kelly [Journal of Medicinal Chemistry, 2018, vol. 61, # 20, p. 9371 - 9385]

60
[ 5308-28-1 ]
C₃₃H₄₁F₂N₇O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 36 h / 60 °C 2: acetic acid; palladium on activated charcoal; hydrogen / methanol / 4 h / 25 °C 3: tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine / <i>tert</i>-butyl alcohol; toluene / 110 °C / Inert atmosphere

Reference： [1]Le Manach, Claire; Paquet, Tanya; Wicht, Kathryn; Nchinda, Aloysius T.; Brunschwig, Christel; Njoroge, Mathew; Gibhard, Liezl; Taylor, Dale; Lawrence, Nina; Wittlin, Sergio; Eyermann, Charles J.; Basarab, Gregory S.; Duffy, James; Fish, Paul V.; Street, Leslie J.; Chibale, Kelly [Journal of Medicinal Chemistry, 2018, vol. 61, # 20, p. 9371 - 9385]

61
[ 5308-28-1 ]
[ 779345-37-8 ]
[ 1374636-03-9 ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9371 - 9385

62
[ 5308-28-1 ]
C₅₆H₆₆N₂O₂₀ [ No CAS ]
C₆₄H₈₂N₄O₂₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide In dimethyl sulfoxide at 25℃; for 24h;

Reference： [1]Brady, Sean F.; Park, Steven; Peek, James; Perlin, David S.; Russo, Riccardo; Suryavanshi, Shraddha; Wang, Han; Xu, Jiayi; Zimmerman, Matthew [ACS Infectious Diseases, 2020, vol. 6, # 9, p. 2431 - 2440]

63
[ 5308-28-1 ]
[ 85822-16-8 ]
4-[4-(2-methylpropyl)piperazin-1-yl]sulfonyl}benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With triethylamine In dichloromethane at 20℃; for 24h;
50 mg	Stage #1: 1-isobutylpiperazine With triethylamine In dichloromethane at 20℃; for 0.166667h; Stage #2: 4-formylbenzene-1-sulfonyl chloride In dichloromethane at 20℃; for 24h;	General procedure: General procedure 4 (23a-aa, 24a-l). To a solution of the corresponding amine (0.29 mmol, 1 Eq.) in DCM (1 ml) was added Triethylamine (0.88 mmol, 3 Eq.). After stirring at room temperature for 10 min., a solution of formylbenzenesulfonyl chloride (21) (0.29 mmol, 1 Eq.) in DCM (1 ml) was added. The reaction mixtures was then stirred at room temperature overnight. After complete consumption of the starting materials - monitored by TLC (DCM/MeOH 9: 1) and UHPLC-MS - The reaction mixture was diluted with a saturated solution NaHCO3 (1 ml). The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. Compound was purified by preparative HPLC.
50 mg	Stage #1: 1-isobutylpiperazine With triethylamine In dichloromethane at 20℃; for 0.166667h; Stage #2: 4-formylbenzene-1-sulfonyl chloride In dichloromethane at 20℃; for 24h;	General procedure: General procedure 4 (23a-aa, 24a-l). To a solution of the corresponding amine (0.29 mmol, 1 Eq.) in DCM (1 ml) was added Triethylamine (0.88 mmol, 3 Eq.). After stirring at room temperature for 10 min., a solution of formylbenzenesulfonyl chloride (21) (0.29 mmol, 1 Eq.) in DCM (1 ml) was added. The reaction mixtures was then stirred at room temperature overnight. After complete consumption of the starting materials - monitored by TLC (DCM/MeOH 9: 1) and UHPLC-MS - The reaction mixture was diluted with a saturated solution NaHCO3 (1 ml). The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. Compound was purified by preparative HPLC.

Reference： [1]Wolter, Madita; Valenti, Dario; Cossar, Peter J.; Hristeva, Stanimira; Levy, Laura M.; Genski, Thorsten; Hoffmann, Torsten; Brunsveld, Luc; Tzalis, Dimitrios; Ottmann, Christian [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8423 - 8436]
[2]Current Patent Assignee: EINDHOVEN UNIVERSITY OF TECHNOLOGY; TAROS CHEMICALS; UNIVERSITY OF CALIFORNIA - WO2021/203016, 2021, A2 Location in patent: Paragraph 0993; 1058; 1070
[3]Current Patent Assignee: EINDHOVEN UNIVERSITY OF TECHNOLOGY; TAROS CHEMICALS; UNIVERSITY OF CALIFORNIA - WO2021/203016, 2021, A2 Location in patent: Paragraph 0993; 1058; 1070

64
[ 5308-28-1 ]
[ 64-18-6 ]
[ 160538-51-2 ]
3-[4-(2-methylpropyl)piperazin-1-yl]-4-nitrobenzaldehyde formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 1-isobutylpiperazine With cesium fluoride; trimethylamine In acetonitrile at 20℃; for 0.333333h; Stage #2: 3-fluoro-4-nitro-benzaldehyde In acetonitrile at 20℃; for 24h; Stage #3: formic acid In water; acetonitrile

Reference： [1]Wolter, Madita; Valenti, Dario; Cossar, Peter J.; Hristeva, Stanimira; Levy, Laura M.; Genski, Thorsten; Hoffmann, Torsten; Brunsveld, Luc; Tzalis, Dimitrios; Ottmann, Christian [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8423 - 8436]

65
[ 5308-28-1 ]
(2-(4-(trifluoromethyl) phenyl) acetyl)-L-tryptophan [ No CAS ]
(S)-N-(3-(1H-indol-3-yl)-1-(4-isobutylpiperazin-1-yl)-1-oxopropan-2-yl)-2-(4-(trifluoromethyl)phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77.6%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	General method for preparation of compounds 3a-3h,4a-4i, 5a-5k, and 6a-6d General procedure: Phenylacetic acid derivative (0.01 mol) or 3-(4-(trifluoromethyl)phenyl) propionic (0.01 mol) and L-tryptophanmethyl ester hydrochloride (0.01 mol) were added to anhydrousDCM; (100 mL), then Et3N (0.04 mol) was added, andthen the mixture was stirred for 10 min. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI)(0.012 mol) and 1-Hydroxybenzotriazole (HOBt)(0.7 mmol) were added and the mixture was stirred overnightat room temperature. Thereafter, the mixture waswashed with 0.1 N sodium hydroxide solution, 0.1 N HCl,and water. The organic layer was concentrated underreduced pressure to produce intermediates 1a-1i. Intermediate1 (5.0 mmol) was dissolved in methanol (20 mL) and heated to 60 oC. 1 N NaOH (10 mL) was added dropwiseand then stirred for 2 h at 60 oC. The reaction mixturewas cooled to room temperature, and the pH was adjusted to2-3 with HCl solution. The cake was filtered, washed withwater, and then dried under reduced pressure to obtainintermediates 2a-2i. Intermediate 2 (1.0 mmol) and variousamino derivatives (1.1 mmol) were added to anhydrousDCM (15 mL) and then Et3N (4.0 mmol), EDCI (1.2 mmol),and HOBt (0.07 mmol) were added. The mixture was stirredovernight at room temperature. Thereafter, the mixture waswashed with water, and then the crude product was crystallizedfrom methanol/water or purified by silica gel forcolumn chromatography (DCM/methanol) to obtain thetargeted product.

Reference： [1]Yu, Ming-jun; Li, Chao; He, Meng; Zhu, Yu-ting; Yang, Rui; Deng, Sheng-song; Meng, Xiao-ming; Yao, Ri-sheng [Medicinal Chemistry Research, 2021, vol. 30, # 11, p. 2069 - 2089]

66
[ 5308-28-1 ]
[ 64-18-6 ]
[ 160538-51-2 ]
3-[4-(2-methylpropyl)piperazin-1-yl]-4-nitrobenzaldehyde formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: 1-isobutylpiperazine With triethylamine; cesium fluoride In acetonitrile at 20℃; for 0.333333h; Stage #2: 3-fluoro-4-nitro-benzaldehyde In acetonitrile at 20℃; Stage #3: formic acid In water; acetonitrile	General procedure: General procedure 1 (13a-u). A solution of the corresponding amine (12a-u) (0.46 mmol, 1.3 Eq.), trimethylamine (1.06 mmol, 3 Eq.) and cesium fluoride (0.03 mmol, 0.1 Eq.) in ACN (1 ml) was stirred at room temperature for 20 min. To the reaction mixture was then added a solution of 3-fluoro-4-nitrobenzaldehyde (11) (0.35 mmol, 1 Eq.) in CAN (0.5 ml). The resulting reaction was then stirred at room temperature for 24 hours. After complete consumption of the starting materials - monitored by TLC (DCM/MeOH 19:1) and UHPLC-MS the mixture was filtered, and filtrate was evaporated under reduced pressure. Compound was purified by preparative HPLC. 3-(3-methoxyazetidin-1-yl)-4-nitrobenzaldehyde (13a). Compound 13a was synthesized using general procedure 1 and 3-azetidinyl methyl ether hydrochloride (12a). The crude reaction was purified using preparative HPLC to afford the desired compound as an orange amorphous solid (26 mg, 30% yield) with a purity of 98% by UHPLC-MS.
30%	Stage #1: 1-isobutylpiperazine With triethylamine; cesium fluoride In acetonitrile at 20℃; for 0.333333h; Stage #2: 3-fluoro-4-nitro-benzaldehyde In acetonitrile at 20℃; Stage #3: formic acid In water; acetonitrile	General procedure: General procedure 1 (13a-u). A solution of the corresponding amine (12a-u) (0.46 mmol, 1.3 Eq.), trimethylamine (1.06 mmol, 3 Eq.) and cesium fluoride (0.03 mmol, 0.1 Eq.) in ACN (1 ml) was stirred at room temperature for 20 min. To the reaction mixture was then added a solution of 3-fluoro-4-nitrobenzaldehyde (11) (0.35 mmol, 1 Eq.) in CAN (0.5 ml). The resulting reaction was then stirred at room temperature for 24 hours. After complete consumption of the starting materials - monitored by TLC (DCM/MeOH 19:1) and UHPLC-MS the mixture was filtered, and filtrate was evaporated under reduced pressure. Compound was purified by preparative HPLC. 3-(3-methoxyazetidin-1-yl)-4-nitrobenzaldehyde (13a). Compound 13a was synthesized using general procedure 1 and 3-azetidinyl methyl ether hydrochloride (12a). The crude reaction was purified using preparative HPLC to afford the desired compound as an orange amorphous solid (26 mg, 30% yield) with a purity of 98% by UHPLC-MS.

Reference： [1]Current Patent Assignee: EINDHOVEN UNIVERSITY OF TECHNOLOGY; TAROS CHEMICALS; UNIVERSITY OF CALIFORNIA - WO2021/203016, 2021, A2 Location in patent: Paragraph 0040; 1008; 1009-1010; 1020
[2]Current Patent Assignee: EINDHOVEN UNIVERSITY OF TECHNOLOGY; TAROS CHEMICALS; UNIVERSITY OF CALIFORNIA - WO2021/203016, 2021, A2 Location in patent: Paragraph 0040; 1008; 1009-1010; 1020

67
[ 5308-28-1 ]
(4,4′,5,5′-tetrachloro-1′H-1,3′-bipyrrole-2,2′-diyl)bis((2-hydroxy-4-(trifluoromethyl)phenyl)methanone) [ No CAS ]
C₃₂H₂₇Cl₃F₆N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium carbonate In 1-methyl-pyrrolidin-2-one Heating; Inert atmosphere;	13 Example 12 Preparation of Compounds 3-15 Using compound 2 (200mg, 311μmol, 1.0eq) as the starting material, K2CO3 (216mg, 1.56mmol, 5.0eq) as the base, N-isobutylpiperazine (0.963mL, 6.22mmol, 20.0eq) as the parent The nuclear reagent, NMP as the solvent, was prepared by referring to the general synthetic method to obtain the crude product.The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v)=3:1) to obtain compound 3-15 (113 mg, 49%) as a pale yellow powder, and part of the sample was further analyzed by normal phase preparative HPLC (PrepSilica OBDTM 5μm, 30×100mm column, flow rate: 25mL/min, temperature: 25°C, n-hexane:isopropanol (v:v)=90:10-85:15-75:25) Purification used to collect spectra and determination of purity data. Purity: 98.1727%;

Reference： [1]Current Patent Assignee: ZEIN BIOTECHNOLOGY - CN113717201, 2021, A Location in patent: Paragraph 0083; 0117-0119

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	5308-28-1	MDL No. :	MFCD00190596
Formula :	C₈H₁₈N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HUUQNWZMQSLPMX-UHFFFAOYSA-N
M.W :	142.24	Pubchem ID :	2052052
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 5308-28-1 ] {[proInfo.proName]}

Quality Control of [ 5308-28-1 ]

Related Doc. of [ 5308-28-1 ]

Product Details of [ 5308-28-1 ]

Safety of [ 5308-28-1 ]

Application In Synthesis of [ 5308-28-1 ]

[ 5308-28-1 ] Synthesis Path-Downstream 1~67

Related Parent Nucleus of
[ 5308-28-1 ]

Piperazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 5308-28-1 ] {[proInfo.proName]}

Quality Control of [ 5308-28-1 ]

Related Doc. of [ 5308-28-1 ]

Product Details of [ 5308-28-1 ]

Safety of [ 5308-28-1 ]

Application In Synthesis of [ 5308-28-1 ]

[ 5308-28-1 ] Synthesis Path-Downstream 1~67

Related Parent Nucleus of [ 5308-28-1 ]

Piperazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Parent Nucleus of
[ 5308-28-1 ]