[ CAS No. 118753-66-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 118753-66-5 * Storage: {[proInfo.prStorage]}

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	Inquiry	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price) ]}	{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]}	{[ item.pr_usastock ]}		{[ item.pr_chinastock ]}	{[ item.pr_remark ]}	Login		Inquiry

Please Login or Create an Account to: See VIP prices and availability

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

For Research Only 120K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 118753-66-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 118753-66-5 ]

SDS Specification

Alternatived Products of [ 118753-66-5 ]

Product Details of [ 118753-66-5 ]

CAS No. :	118753-66-5	MDL No. :	MFCD08274502
Formula :	C₉H₁₉N₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QMZFIRHRGPLKEV-UHFFFAOYSA-N
M.W :	201.27	Pubchem ID :	22029174
Synonyms :

Calculated chemistry of [ 118753-66-5 ] Expand+

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.89
Num. rotatable bonds :	3
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	61.3
TPSA :	58.8 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.4 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.15
Log Po/w (XLOGP3) :	0.18
Log Po/w (WLOGP) :	-0.35
Log Po/w (MLOGP) :	0.54
Log Po/w (SILICOS-IT) :	-0.75
Consensus Log Po/w :	0.35

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.0
Solubility :	20.0 mg/ml ; 0.0993 mol/l
Class :	Very soluble
Log S (Ali) :	-0.97
Solubility :	21.4 mg/ml ; 0.106 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.21
Solubility :	125.0 mg/ml ; 0.619 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.57

Safety of [ 118753-66-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 118753-66-5 ]

* 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 [ 118753-66-5 ]
Downstream synthetic route of [ 118753-66-5 ]

[ 118753-66-5 ] Synthesis Path-Upstream 1~5

1
[ 877177-42-9 ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: With acetic acid; zinc In methanol at 0 - 20℃; for 2 h; Stage #2: With sodium hydrogencarbonate In methanol; water	To a solution of the compound obtained in the above step (1) (730 mg) in methanol (10 mL) was added zinc powder (1.1 g) at room temperature and thereto was added dropwise acetic acid (10 mL) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered and to the filtrate was added an aqueous sodium hydrogencarbonate solution to basify. After stirring, the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to obtain l-amino-4-tert- butoxycarbonylpiperazine (730 mg, yield: 100 percent) as a pale yellow oil.
58%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 25℃; for 12 h;	To a solution of 1 ,1 -dimethylethyl 4-nitroso-1 -piperazinecarboxylate (500 mg, 2.33 mmol) in THF (23 mL) at O0C was added dropwise a solution of LAH (5.8 mL, 5.8 mmol, 1 M in THF). The reaction mixture warmed to 25°C over 12h and was subsequently quenched by dropwise addition of a saturated solution of potassium sodium tartrate. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4) and concentrated at 250C yielding a yellow oil that was used without further purification (270 mg, 58percent): LCMS (ES) m/e 202 (M+H)+.

Reference： [1] Patent: WO2007/46550, 2007, A1, . Location in patent: Page/Page column 120
[2] Patent: WO2006/20561, 2006, A2, . Location in patent: Page/Page column 61
[3] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 247 - 258
[4] Patent: US10213433, 2019, B2, . Location in patent: Paragraph 0680

2
[ 883554-88-9 ]
[ 118753-66-5 ]

Reference： [1] Patent: US2009/275594, 2009, A1, . Location in patent: Page/Page column 19

3
[ 24424-99-5 ]
[ 30651-60-6 ]
[ 118753-66-5 ]

Reference： [1] Patent: US2003/199689, 2003, A1, . Location in patent: Page/Page column 76

4
[ 118753-70-1 ]
[ 118753-66-5 ]

Reference： [1] Patent: US4839358, 1989, A,

5
[ 57260-71-6 ]
[ 118753-66-5 ]

Reference： [1] Patent: WO2015/22663, 2015, A1,
[2] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 247 - 258
[3] Patent: US10213433, 2019, B2,

[ 118753-66-5 ] Synthesis Path-Downstream 1~23

1
[ 118753-66-5 ]
[ 443956-14-7 ]
[ 877177-43-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With benzotriazol-1-ol; 1,2-dichloro-ethane; In dichloromethane; N,N-dimethyl-formamide; for 12.0h;	To a solution of 1 ,1-dimethylethyl 4-amino-1 -piperazinecarboxylate (270 mg, 1.34 mmol) in DCM-DMF (4:1 , 15 ml_) were added 3-oxo-3,4-dihydro-2H-pyrido[3,2- i?][1 ,4]thiazine-6-carboxylic acid (283 mg, 1.34 mmol), EDC (250 mg, 1.61 mmol) and HOBT (217 mg, 1.61 mmol). After 12h, the solution was concentrated and the residue purified via column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) yielding the title compound as a yellow foam (412 mg, 78 %): LCMS (ES) m/e 394 (M+H)+.

Reference： [1]Patent: WO2006/20561,2006,A2 .Location in patent: Page/Page column 62

2
[ 24424-99-5 ]
[ 30651-60-6 ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16.0h;	(i) 4-Amino-piperazine-1-carboxylic acid tert-butyl ester To a solution of Piperazin-1-ylamine in 20 ml THF and 1.37 ml NEt3, 2.2 g Boc2O in 5 ml THF were added dropwise at 0 C. The reaction mixture was stirred for 16 h at RT then 50 ml ethyl acetate and 20 ml water were added. The organic layer was separated, washed with brine and dried over Na2SO4. After removal of the solvent under reduced pressure the product was obtained as a white solid. Yield: 1.53 g.

Reference： [1]Patent: US2003/199689,2003,A1 .Location in patent: Page/Page column 76

3
[ 118753-70-1 ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; hydrazine hydrate;	Step B: Tertbutyl 4-amino-1-piperazine carboxylate Under an inert atmosphere at ambient temperature, 15.3 g of the product of Step A and 80 ml of hydrazine hydrate were mixed together and then 150 ml of a saturated aqueous solution of ammonium chloride were added. Extraction was done with methylene chloride and the organic phase was washed with an aqueous solution of ammonium chloride, dried, and the solvent was eliminated under reduced pressure. After chromatography on silica (eluent:methylene chloride - methanol, 100/7) 5 g of the expected product were obtained.

Reference： [1]Patent: US4839358,1989,A

4
[ 118753-66-5 ]
[ 350-46-9 ]
[ 333986-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; water;	(1) <strong>[118753-66-5]4-Amino-1-tert-butoxycarbonylpiperazine</strong> (3.00 g), 4-fluoronitrobenzene (2.54 g) and N,N-diisopropylethylamine (8.82 g) were dissolved in N-methyl-2-pyrrolidone (30 mL), and the mixture was stirred at 80C for 18 hr. The reaction mixture was added to water and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give 1-tert-.butoxycarbonyl-4-(4-nitrophenyl)aminopiperidine (2.55 g) as a white solid.

Reference： [1]Patent: EP1308439,2003,A1

5
[ 118753-66-5 ]
[ 935259-85-1 ]
3-[N-(4-tert-butoxycarbonylpiperazin-1-yl)-carbamoyl]-1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methoxy-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With benzotriazol-1-ol; triethylamine; In dichloromethane; at 20℃;	To a solution of 3-carboxyl-l-(2-chlorophenyl)-5-(4-chlorophenyl)-4- EPO <DP n="52"/>methoxy-lH-pyrazole (1.96 g, compound obtained in Reference Example 1(6)) in methylene chloride (20 mL) was added l-amino-4-tert-butoxycarbonylpiperazine (730 mg, compound obtained in Reference Example 16(2)), water-soluble carbodiimide HCl (1.0 g), 1-hydroxybenzotriazole hydrate (827 mg) and triethylamine (753 muL), and the mixture was stirred at room temperature overnight. To the reaction mixture was added an aqueous sodium hydrogencarbonate solution and the mixture was stirred and extracted with chloroform. The extract was concentrated in vacuo and the crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate = 60/40 to 40/60) to obtain 3-[N-(4-tert-butoxycarbonylpiperazin-l-yl)- carbamoyl] -l-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methoxy-lH-pyrazole (1.56 g; yield: 79 %) as a colorless solid. MS(APCI)m/z; 546/548 [M+H]+

Reference： [1]Patent: WO2007/46550,2007,A1 .Location in patent: Page/Page column 49-50

6
[ 877177-42-9 ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
100%		To a solution of the compound obtained in the above step (1) (730 mg) in methanol (10 mL) was added zinc powder (1.1 g) at room temperature and thereto was added dropwise acetic acid (10 mL) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered and to the filtrate was added an aqueous sodium hydrogencarbonate solution to basify. After stirring, the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to obtain l-amino-4-tert- butoxycarbonylpiperazine (730 mg, yield: 100 %) as a pale yellow oil.
96%	With ammonium chloride; zinc; In tetrahydrofuran; water; at 20℃;	To a stirred solution of tert-butyl 4-nitrosopiperazine--carboxylate (0 500 g, 2 32 mmol, 1 equiv) in THF: H20 (10: 10 mL) was added NLLCl (1.98 g, 37. 17 mmol, 16.0 equiv) and then Zn dust (1.21 g, 18.58 mmol, 8.0 equiv) was added portion wise. After completion of addition the reaction mixture was stirred at RT for overnight. Progress of the reaction was monitored by LCMS Reaction mixture was diluted with water (100 mL) and filtered off over celite bed and filtrate was extracted with DCM (100 mL c 2) Organic layer was separated and dried over anhydrous NarSCrt and concentrated under reduced pressure to obtain tert-butyl 4- aminopiperazine-l-carboxylate (0.420 g, 96 % Yield) as a yellow semi solid. LCMS 202.3 i M l l f : T-I NMR (400MHz, Chloroform-d) d 3.47 (br s , 4 H), 3.14 (br. s? 2 H), 2 56 (br. s., 4 H), 1.45 (s, 9 H).
86%	With acetic acid; zinc; In methanol; at 0 - 20℃; for 2.0h;Inert atmosphere;	1-Boc-4-nitrosopiperazine (1.46 g, 6.8 mmol) was dissolved in 10 mL of methanol at room temperature,Zinc powder (2.20 g, 33.8 mmol) was added, cooled to 0 C, acetic acid (20 mL) was slowly added dropwise, and then heated to room temperature under nitrogen protection and stirred for 2 hours.After the reaction was completed, the solution was filtered, and the pH was adjusted to 9-10 with a saturated sodium bicarbonate aqueous solution, and 40 mL of water was added.Extract three times with 180 mL of dichloromethane, combine the organic phases, dry over anhydrous sodium sulfate, filter,Spin-drying and purification to obtain compound 1-Boc-4-aminopiperazine (1.18 g, yield 86%)

58%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 25℃; for 12.0h;	To a solution of 1 ,1 -dimethylethyl 4-nitroso-1 -piperazinecarboxylate (500 mg, 2.33 mmol) in THF (23 mL) at O0C was added dropwise a solution of LAH (5.8 mL, 5.8 mmol, 1 M in THF). The reaction mixture warmed to 25C over 12h and was subsequently quenched by dropwise addition of a saturated solution of potassium sodium tartrate. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4) and concentrated at 250C yielding a yellow oil that was used without further purification (270 mg, 58%): LCMS (ES) m/e 202 (M+H)+.
	With acetic acid; zinc; In water; at 0℃; for 5.0h;	General procedure: To a well-stirred solution of an appropriate intermediate (7a-e) (0.10mol) in a mixed solution of AcOH (100mL) and H2O (100mL) was added zinc powder (26.2g,0.40mol) at 0C, followed by stirring for 6-8hat the same temperature. After completion of the reaction as indicated by TLC, the resulted mixture was filtered and the filtrate was concentrated under reduced pressure. Then ethyl acetate (100mL) was added and the misture was stirred for 0.5hat the room temperature. The mixture was filtered, and the filtrate was concentrated under reduced presusre to yield the corresponding intermediates 8a-e.
	With hydrogenchloride; zinc; In methanol; water; at 0℃; for 0.5h;	(0680) In a 100 ml round-bottomed flask was added Compound 232A (0.15 g) and zinc (1 g) in water/methanol (1:1, 10 ml) to give a suspension. The mixture was cooled to 0 C. 12N Aqueous HCl (2 ml) was added slowly, and the mixture was stirred at 0 C. for 30 minutes. 2N Aqueous NaOH solution was used to adjust the mixture to basic pH. The mixture was filtered, and extracted with ether (3×30 ml). After drying over Na2SO4, filtration, and concentration, the crude product was added to a silica gel column (Analogix, SF15-12 g,) and purified by eluting with 0-25% ethyl acetate in hexane.

Reference： [1]Patent: WO2007/46550,2007,A1 .Location in patent: Page/Page column 120
[2]Patent: WO2019/236710,2019,A1 .Location in patent: Paragraph 0286
[3]Patent: CN110483514,2019,A .Location in patent: Paragraph 0395; 0399; 0402; 0403
[4]Patent: WO2006/20561,2006,A2 .Location in patent: Page/Page column 61
[5]European Journal of Medicinal Chemistry,2018,vol. 158,p. 247 - 258
[6]Patent: US10213433,2019,B2 .Location in patent: Page/Page column 162
[7]European Journal of Medicinal Chemistry,2020,vol. 185

7
[ 118753-66-5 ]
[ 534595-43-2 ]
4-({1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-amino)-piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		(ii) 4-({1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-amino)-piperazine-1-carboxylic acid tert-butyl ester To a solution of 1 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid and 1.3 ml NEM in 8 ml DCM, 914 mg TOTU were added and the mixture was stirred for 30 min at RT. Then 673 mg <strong>[118753-66-5]4-Amino-piperazine-1-carboxylic acid tert-butyl ester</strong> were added and the reaction was stirred over night. After removal of the solvent under reduced pressure the residue was directly purified by chromatography on silica gel eluding with an ethyl acetate/heptane gradient. Yield: 1.1 g.

Reference： [1]Patent: US2003/199689,2003,A1 .Location in patent: Page/Page column 76

8
[ 118753-66-5 ]
[ 541-41-3 ]
C₁₂H₂₃N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To Compound 33 prepared as in Intermediate Example 1 (8.29 g, 41.2 mmol) and pyridine (6.0 mL, 74.2 mmol) in MeCN (120 mL) was added dropwise ethyl chloroformate (5.9 mL, 61.9 mmol). The resulting mixture was stirred at room temperature for 3 h, then partitioned between EtOAc and saturated aqueous NaHCO3, dried with Na2SO4, and concentrated in vacuo to yield a residue, which was used in the next step without further purification. MS 274 (M+1)+

Reference： [1]Patent: US2009/275594,2009,A1 .Location in patent: Page/Page column 19

9
[ 883554-88-9 ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
		The white solid from step A in ethanol (50 mL) was cooled to 0 C., and a pre-mixed solution of NaOCl (10-13% active chlorine, 43.4 mL) and 15% NaOH (78.0 mL) was added dropwise via an addition funnel. The ice bath was removed and the resulting mixture was stirred at room temperature for 1 h. 1N HCl was added to the resulting mixture until the pH of the solution was about pH 1, and the resulting mixture was stirred at room temperature for an additional 15 min. The pH of the solution was made basic with saturated aqueous potassium carbonate, and the resulting solution concentrated in vacuo to half the volume, then extracted three times with EtOAc, the combined organics were dried with Na2SO4, and concentrated in vacuo to yield the title compound, which was used in the next step without further purification. MS 202 (M+1)+

Reference： [1]Patent: US2009/275594,2009,A1 .Location in patent: Page/Page column 19

10
[ 118753-66-5 ]
[ 1452467-35-4 ]

Reference： [1]Patent: US2013/225554,2013,A1
[2]Patent: WO2014/91268,2014,A1

11
[ 118753-66-5 ]
[ 1452467-36-5 ]

Reference： [1]Patent: US2013/225554,2013,A1
[2]Patent: WO2014/91268,2014,A1

12
[ 118753-66-5 ]
[ 1174020-25-7 ]
[ 1452467-34-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Step 1. tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate (206) To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added <strong>[118753-66-5]tert-butyl 4-aminopiperazine-1-carboxylate</strong> 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4-dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1H, m), 1.95 (2H, m), 2.38 (1H, m), 2.70 (1H, d, J=12.0 Hz), 2.76 (4H, m), 2.99 (1H, d, J=12.0 Hz), 3.30 (1H, m), 3.57 (4H, m), 3.89 (1H, d, J=8.0 Hz), 4.90 (1H, d, J=11.6 Hz), 5.04 (1H, d, J=12.0 Hz), 7.21 (5H, m), 8.90 (1H, br s).
88%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added te/f-butyl 4-aminopiperazine-1-carboxylate 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4- dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give terf-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo- 1 ,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1 H, m), 1.95 (2H, m), 2.38 (1 H, m), 2.70 (1 H, d, J = 12.0Hz), 2.76 (4H, m), 2.99(1H, d, J = 12.0 Hz), 3.30 (1 H, m), 3.57 (4H, m), 3.89 (1 H, d, J = 8.0 Hz), 4.90 (1H, d, J = 11.6 Hz), 5.04 (1 H, d, J = 12.0 Hz), 7.21 (5H, m), 8.90 (1 H, br s).

Reference： [1]Patent: US2013/225554,2013,A1 .Location in patent: Paragraph 1239; 1240; 1241
[2]Patent: WO2014/91268,2014,A1 .Location in patent: Page/Page column 215

13
[ 118753-66-5 ]
[ 853908-81-3 ]
tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30 g	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 2.0h;	[00229] Step-3: Synthesis tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4- yl)amino) piperazine- 1 -carboxylate, 4: [00230] DIPEA (26.72mL, 0.15712mo1) was added to a stirred solution of 6- Bromo-4-chloro-7-fluoro-3-nitroquinoline, 9 (24g, 0.07856mo1) and <strong>[118753-66-5]tert-butyl 4-aminopiperazine-1-carboxylate</strong> (18.97g, 0.09427mo1) in DMF, 200mL at 0 00. The reaction mixture was allowed to room temperature and stirred for 2h. Reaction was monitored by TLC (30%EtOAc in hexane), after completion of reaction, diluted with water (l5OmL), the precipitated yellow solid was filtered-off, washed with water and dried under vacuum. The crude material was purified by column chromatography by using5i02 (15% EtOAc in Hexane) to afford of tert-butyl4-((6-bromo-7-fluoro-3-nitroquinolin-4- yl) amino) piperazine-1-carboxylate, 4 (30g, 81%). 1H NMR (300MHz, CDCI3): O 10.42 (5, 1H), 10.22-10.19 (d, 1H), 9.36 (5, 1H), 7.67-7.64 (d, 1H), 4.35-4.25 (t, 2H), 3.46-3.08 (t, 4H), 2.84-2.65 (t, 2H), 1.50 (5, 9H); LCMS: mlz= 469.9 (M+1) and 471.9 (M+2).

Reference： [1]Patent: WO2015/22663,2015,A1 .Location in patent: Paragraph 00229; 00230

14
[ 57260-71-6 ]
[ 118753-66-5 ]

Reference： [1]Patent: WO2015/22663,2015,A1
[2]European Journal of Medicinal Chemistry,2018,vol. 158,p. 247 - 258
[3]Patent: US10213433,2019,B2
[4]European Journal of Medicinal Chemistry,2020,vol. 185
[5]Patent: CN110483514,2019,A

15
tert-butyl 4-nitropiperazine-1-carboxylate [ No CAS ]
[ 118753-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; zinc; In tetrahydrofuran; water; for 0.5h;	[00227] Step-2: Synthesis of tert-butyl 4-aminopiperazine-1-carboxylate, 3:[00228] To a stirred solution of tert-butyl 4-nitropiperazine-1-carboxylate, 2 (22g, 0.09513mo1) in THF (200mL), a saturated solution of NH4CI (81.4g, 1.521mo1 in water l5OmL) was added. Zn (49.7g, 0.760mo1) was added portion wise and the resulting suspension was stirred for 30mm. The reaction was monitored by TLC (10% MeOH in DCM). The reaction mass was filtered through celite-pad and washed withDCM. The Aqueous layer was extracted with DCM (3x 200mL). The combined organic layers were washed with brine solution, dried over anhydrous Na2504 and concentrated to dryness to afford crude tert-butyl 4-aminopiperazine-1-carboxylate, 3 (18g, 83%). 1H NMR (DMSO-d6, 400MHz): O 3.29-3.19 (m, 4H), 2.55-2.62 (m, 2H), 2.45-2.38 (m, 2H), 1.38 (5, 9H).

Reference： [1]Patent: WO2015/22663,2015,A1 .Location in patent: Paragraph 00227; 00228

16
[ 118753-66-5 ]
tert-butyl 4-((3-amino-6-bromo-7-fluoroquinolin-4-yl)amino)piperazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/22663,2015,A1

17
[ 118753-66-5 ]
tert-butyl 4-(8-bromo-7-fluoro-1H-imidazo[4,5-c]quinolin-1-yl)piperazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/22663,2015,A1

18
[ 118753-66-5 ]
tert-butyl 4-(8-(2-chloro-4-(pyrimidin-2-yloxy)phenyl)-7-fluoro-1H-imidazo[4,5-c]quinolin-1-yl)piperazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/22663,2015,A1

19
[ 118753-66-5 ]
[ 108-12-3 ]
C₁₄H₂₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
120 mg	With N-ethyl-N,N-diisopropylamine; In chloroform; at 20℃; for 3.0h;	(1) The compound 1 (100 mg) and diisopropylethylamine (240 mL) were dissolved in chloroform, isovaleryl chloride(217 mL) was added to the solution, and the reaction mixture was stirred for 3 hours at room temperature. Thereaction mixture was diluted with a saturated aqueous solution of sodium bicarbonate, and extracted twice withchloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated underreduced pressure. The resulting residue was suspended and washed in a mixed solution of ethyl acetate-hexane,taken by filtration, and dried to give the compound 2 (120 mg) as a colorless solid.MS (APCI) 286 [M+H]+

Reference： [1]Patent: EP3135668,2017,A1 .Location in patent: Paragraph 0346

20
[ 118753-66-5 ]
4-(4-chloro-6-(thiophen-2-yl)-1,3,5-triazin-2-yl)morpholine [ No CAS ]
tert-butyl 4-(4-morpholino-6-(thiophen-2-yl)-1,3,5-triazin-2-yl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16.0h;	General procedure: Chloro derivative (1 mol), amine (1 mol) and K2CO3 (2mol) were taken in DMF (10 v). The reaction mixture washeated to 100 C, stirred for 16 h. Then the reaction mixturewas cooled to room temperature, diluted with water (50 v) extracted with EtOAC (2 x 50 v). Combined organic layerswere dried over anhydrous sodium sulphate, evaporated thesolvent in vacuo. Crude products were purified by columnchromatography.

Reference： [1]Letters in drug design and discovery,2018,vol. 15,p. 181 - 192

21
[ 118753-66-5 ]
[ 843647-60-9 ]
N-{3-{2-fluoro-4'-[(4-tert-butoxycarbonylpiperazin-1-yl)iminomethyl]-biphenyl-4-yl}-2-oxo-1,3-oxazolidine-5-(S)-ylmethyl}-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: To a well-stirred solution of intermediate 5 (2g, 5.6mmol) in C2H5OH(60mL) was added a drop of AcOH. The resulted mixture was refluxed for 0.5h. Then intermediates 8a (2.95g) was added, followed by stirring for 10hat the same temperature. After cooled to room temperature, The resulting solid was collected by filtration and dried to give the target compounds 9a as a light yellow solid in 82% yield.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 158,p. 247 - 258

22
[ 118753-66-5 ]
(S)-N-(3-(2-fluoro-3'-hydroxy-4'-formylbiphenyl-4-yl)-2-oxo-1,3-oxazolidine-5-yl)acetamide [ No CAS ]
(S)-N-(3-(2-fluoro-3'-hydroxy-4’-((4-tert-butoxycarbonylpiperazin-1-yl)iminomethyl)biphenyl-4-yl)-2-oxo-1,3-oxazolidine-5-ylmethyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With acetic acid; In ethanol; at 78℃; for 2.0h;	General procedure: To a well-stirred solution of intermediate 5a (2.0 g,5.29 mmol) in ethanol (10 mL) was added 1-amino-4-methylpiperazine 9a (0.61 g, 5.29 mmol) and a drop of acetic acid,and the mixturewas stirred at 78 C for 2 h. The mixturewas cooledto room temperature and the resulting solid was collected byfiltration and purified by column chromatography to give the targetcompounds 6a-1 as a yellow solid in 75% yield. M.p: 228-230 C;

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 185

23
[ 118753-66-5 ]
(S)-N-(3-(2-fluoro-3'-fluoro-4'-formylbiphenyl-4-yl)-2-oxo-1,3-oxazolidine-5-ylmethyl)acetamide [ No CAS ]
(S)-N-(3-(2-fluoro-3'-fluoro-4’-((4-tert-butoxycarbonylpiperazin-1-yl)iminomethyl)biphenyl-4-yl)-2-oxo-1,3-oxazolidine-5-ylmethyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With acetic acid; In ethanol; at 78℃; for 2.0h;	General procedure: To a well-stirred solution of intermediate 5a (2.0 g,5.29 mmol) in ethanol (10 mL) was added 1-amino-4-methylpiperazine 9a (0.61 g, 5.29 mmol) and a drop of acetic acid,and the mixturewas stirred at 78 C for 2 h. The mixturewas cooledto room temperature and the resulting solid was collected byfiltration and purified by column chromatography to give the targetcompounds 6a-1 as a yellow solid in 75% yield. M.p: 228-230 C;

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 185

Recommend Products

Same Skeleton Products

Related Products

Isomers

Technical Information

• Acyl Group Substitution • Bouveault-Blanc Reduction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • Ester Cleavage • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Amines • Reactions with Organometallic Reagents • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Ugi Reaction

Historical Records

Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
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. 118753-66-5 ] {[proInfo.proName]}

Quality Control of [ 118753-66-5 ]

Related Doc. of [ 118753-66-5 ]

Product Details of [ 118753-66-5 ]

Calculated chemistry of [ 118753-66-5 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 118753-66-5 ]

Application In Synthesis of [ 118753-66-5 ]

[ 118753-66-5 ] Synthesis Path-Upstream 1~5

[ 118753-66-5 ] Synthesis Path-Downstream 1~23

Technical Information

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry