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5-Bromo[1,2,4]triazolo[1,5-a]pyridin-2-amine

5-Bromo[1,2,4]triazolo[1,5-a]pyridin-2-amine

5-Bromo[1,2,4]triazolo[1,5-a]pyridin-2-amine

CAS No.: 1010120-55-4

Category Products

Cat.NO.:A207241 Purity:98%

Product Details of [ 1010120-55-4 ]

CAS No. :	1010120-55-4
Formula :	C₆H₅BrN₄
M.W :	213.04
SMILES Code :	NC1=NN2C(Br)=CC=CC2=N1
MDL No. :	MFCD11655928
InChI Key :	TVGFHUIJNZRKFW-UHFFFAOYSA-N
Pubchem ID :	25215939

Safety of [ 1010120-55-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 1010120-55-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	45.09
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	56.21 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.53
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.42
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.08
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.58
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.45
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.21

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.66
Solubility	0.465 mg/ml ; 0.00218 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.21
Solubility	1.33 mg/ml ; 0.00624 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.21
Solubility	1.3 mg/ml ; 0.00612 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.59 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12’782’590 molecules and tested on 40 external molecules (r² = 0.94)	2.14

Application In Synthesis of [ 1010120-55-4 ]

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

Downstream synthetic route of [ 1010120-55-4 ]

[ 1010120-55-4 ] Synthesis Path-Downstream 1~35

2
[ 288-13-1 ]
[ 1010120-55-4 ]
[ 1124382-69-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium hydroxide; at 110℃;	Intermediate A12 : 5-flH-pyrazol-l-yl)[l,2,41triazolo[l,5-alpyridin-2-amine; Intermediate A125-bromo[l,2,4]triazolo[l,5-a]pyridin-2-amine ((A3); 1,06 g; 5.0 mmol; 1.0 eq.), pyrazole (3.40 g; 50.0 mmol; 10 eq.) and potassium hydroxide (842 mg; 15.0 mmol; 3.0 eq.) were melted and stirred overnight at 110 0C. After this time, reaction mixture was cooled to rt poured into water and extracted with Et2O. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the title compound as a white solid (650 mg, 65%). HPLC, Rt: 1.22 min. (purity 96.6%). LC/MS, M+(ESI): 201.0.

References: [1]Patent: WO2009/27283,2009,A1 .Location in patent: Page/Page column 61.

3
[ 1010120-55-4 ]
[ 98-88-4 ]
[ 1124382-75-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine; In dichloromethane; for 4h;Heating / reflux;	Intermediate Bl : N-f5-bromo[l,2,41triazolo[l,5-alpyridin-2-yl)benzamide; Intermediate BlBenzoyl chloride (4.40 g; 31.4 mmol; 2.0 eq.) was added to a suspension of 5- bromo[l,2,4]triazolo[l,5-a]pyridin-2-amine ((A3), 3.34 g; 15.7 mmol; 1.0 eq.) in pyridine (2.53 mL; 31.4 mmol; 2.0 eq.) and DCM (60 mL). The reaction mixture was then heated at <n=”69″/>reflux for 4 hours, after which it was cooled down to rt. Diethyl ether was added to the reaction mixture and the solid which precipitated was filtered off. The precipitate was resuspended in an aqueous mixture (pH 4/5), filtered and dried under vacuum to give the title compound as a white powder (4.97 g, quant, yield). HPLC, Rt: 2.40 min. (purity 93.4%), LC/MS, M+(ESI): 317.1, M (ESI): 315.1.

References: [1]Patent: WO2009/27283,2009,A1 .Location in patent: Page/Page column 67-68.

4
[ 1010120-55-4 ]
[ 63503-60-6 ]
[ 1111106-76-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); at 150℃; for 1h;Microwave irradiation;	A suspension of 5-bromo[l,2,4]triazolo[l,5-alpha]pyridin-2-amine (5.1 g, 24 mmol, 1 equiv), 3-chlorophenylboronic acid (3.8 g, 24 mmol, 1.0 equiv), cesium carbonate (9.4 g, 29 mmol, 1.2 equiv), tetrakistriphenylphosphine palladium (2.7 g, 2.4 mmol, 0.1 equiv) was heated to 150 C for 1 h under <n=”96″/>microwave irradiation. The reaction mixture was diluted with ethyl acetate and filtered through Celite. The filtrate was washed with saturated aqueous sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (30% ethyl acetate in petroleum ether) provided product as a solid (3.5 g, 61%). LCMS (ESI) m/z: 244.9.
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 5h;Reflux;	Compound 14Compound 13 (750 mg, 3.5 mmol) was dissolved in toluene/ethanol (1 :1, 20 ml), to which was added 2M aqueous Na2CO3 (3.5 ml) and 3- chlorophenylboronicacid (1.1 g, 7.0 mmol). Pd (PPh3) 4 (202 mg) was added last, the mixture was flushed with nitrogen and refluxed for 5 hours in a sealed tube. The reaction mixture was allowed to cool.The reaction solvent was removed and the residue was purified on silica gel (ethylacetate : hexanes 50%) to give 514mg of compound 14 as white solid. LC-MS (ESI, positive): 247 [M+H]+.

References: [1]Patent: WO2009/155565,2009,A1 .Location in patent: Page/Page column 94-95.
[2]Patent: WO2009/17954,2009,A1 .Location in patent: Page/Page column 27; 28.

5
[ 1010120-59-8 ]
[ 1010120-55-4 ]

Yield	Reaction Conditions	Operation in experiment
79.5%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 70℃; for 3.5h;	A solution was ethyl [(6-methylpyridin-2-yl)carbamothioyl]carbamate (43.7 g, 0.144 mmol, 1 equiv), hydroxylamine hydrochloride (51.3 g, 0.738 mmol, 5.13 equiv), and diisopropylethylamine (75.2 mL, 0.432 mmol, 3.00 equiv) in 1:1 methanol / ethanol (500 mL) was heated to 70 0C for 3.5 h. The reaction mixture was cooled to 24 C, and the resulting solids were filtered.The solids were rinsed with cold water (2 x 100 mL) and dried in vacuo (~1 mm Hg) to afford product as a white solid (24.4 g, 79.5%). 1H NMR (400 MHz, OMSO-d6), delta: 7.32-7.38 (m, 2 H), 7.21 (m, 1 H), 6.23 (br s, 2 H).
78%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20℃; for 4h;Reflux;	Step (ii)To a suspension of hydroxylamine hydrochloride (85.5g, 1230mmol) in EtOH/MeOH (1 : 1, 400mL) was added DIPEA (129mL, 738mmol) and the mixture was stirred at rt (20C) for lh. l-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (74.7g, 246mmol) was then added and the mixture slowly heated to reflux (Note: bleach trap required to quench H2S evolved). After 3h at reflux the mixture was allowed to cool overnight. The resulting precipitate was removed by filtration and washed thoroughly with water followed by diethylether and air-dried to afford the desired compound as a white solid (41g, 78%). LCMS (method A), (M+H+) 213/215, RT = 0.70min.
74%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20 – 60℃; for 20h;Product distribution / selectivity;	To a stirred suspension of hydroxylamine hydrochloride (20.0 g, 288 mmol) and N,N-diisopropylethylamine (30.0 mL, 172 mmol) in a mixture of methanol (80 mL) and ethanol (80 mL) was added N-(3-bromo-2-pyridinyl)-N’-carboethoxy-thiourea. The mixture was stirred for 2 hours at room temperature then heated to 600C for 18 hours. The suspension was cooled to room temperature, filtered and rinsed with methanol, water then methanol. The recovered off-white solid was consistent for 5-bromo-[l,2,4]triazolo[l,5- a]pyridin-2-ylamine (9.04 g, 74%). 1H NMR (400 MHz, (D3C)2SO, delta, ppm): 7.36 (m, 2H), 7.22 (d, J= 7.5 Hz, IH), 6.27 (br s, 2H) MS = 213, 215 (MH)+.

	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20 – 60℃; for 5h;	Compound 13To a stirred suspension of hydroxylamine hydrochloride (959.1 g, 13.8 mmol) and DIPEA (1.2 g, 9.2 mmol) in methanol/ethanol (1 : 1 , 50 ml) was added compound 12 (1.4 g, 4.6 mmol) as solid. The mixture was stirred at room temperature for 2 hours, followed by 3hours at 600C. The reaction mixture wasallowed to cool, diluted with CH2Cl2, which was then washed with water (2chi80 ml), the organic phase was evaporated and the residue was chromatographed in MeOH/ CH2Cl2 (8% -10%) to afford 750 mg of compound 13 as a white solid. LC-MS (ESI, positive): 215 [M+H]+.
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20℃;Reflux;	To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1,900 mL) is added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture is stirred at room temp. (2O0C) for 1 h. l-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) may then be added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3 h at reflux, the mixture is allowed to cool and filtered to collect the precipitated solid. Further product may be collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1 :1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford (3) as a solid. No further purification is required. 1H (400 MHz, DMSO-d6) delta: 7.43-7.34 (2H, m, 2 Hz aromatic-H), 7.24 (IH, dd, J 6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, b, NH2); m/z 213/215 (1 :1, M+H+, 100%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20℃;Reflux;	To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) is added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture is stirred at room temp. (20 C.) for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) may then be added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3 h at reflux, the mixture is allowed to cool and filtered to collect the precipitated solid. Further product may be collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford the triazolopyridine derivative (3) as a solid. The compound may be used as such for the next step without any purification. 1H (400 MHz, DMSO-d6) delta 7.43-7.34 (2H, m, 2* aromatic-H), 7.24 (1H, dd, J 6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; water; for 3h;Reflux;	1.1.2 5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (3) To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) is added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture is stirred at room temp. (20 C.) for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) is then added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3 h at reflux, the mixture is allowed to cool and filtered to collect the precipitated solid. Further product is collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford the triazolopyridine derivative (3) as a solid. The compound may be used as such for the next step without any purification. 1H (400 MHz, DMSO-d6) delta 7.43-7.34 (2H, m, 2*aromatic-H), 7.24 (1H, dd, J 6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20℃; for 3h;Reflux;	To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH(1:1, 900 mL) was added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture wasstirred at room temp. (20 oq for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g,0.293 mol) was then added and the mixture slowly heated to reflux (Note: bleach scrubber wasrequired to quench H2S evolved). After 3 h at reflux, the mixture was allowed to cool and filtered tocollect the precipitated solid. Further product was collected by evaporation in vacuo of the filtrate,addition of H20 (250 mL) and filtration. The combined solids were washed successively with H20 (250 mL), EtOH/MeOH (1:1, 250 mL) and Et20 (250 mL) then dried in vacuo to afford thetriazolopyridine derivative (3) as a solid. The compound was used as such in the next step without anypurification.[00159] 1H ( 400 MHz, DMSO-d6) 8 7.43-7.34 (2H, m, 2 x aromatic-H), 7.24 (lH, dd, J 6.8 and 1.8Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; for 3h;Reflux;	1.1.2.2. Step ii): 5-Bromo-[1,2,4]triazolo[1,5-a]kyridin-2-ylamine To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) is added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture is stirred at room temp. (20 C.) for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) is then added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3h at reflux, the mixture is allowed to cool and filtered to collect the precipitated solid. Further product is collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford the triazolopyridine derivative (3) as a solid. The compound may be used as such for the next step without any purification. 1H (400 MHz, DMSO-d6) delta 7.43-7.34 (2H, m, 2×aromatic-H), 7.24 (1H, dd, J6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; at 20℃;Reflux;	Step ii : 5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) is adde Details Products CAS 50-54-4 Read more Products CAS 52-47-1 Read more Products CAS 55-16-3 Read more Reviews There are no reviews yet. Be the first to review “5-Bromo[1,2,4]triazolo[1,5-a]pyridin-2-amine” 取消回复您的邮箱地址不会被公开。必填项已用 * 标注 Your rating * Your review * Name * Email * 在此浏览器中保存我的显示名称、邮箱地址和网站地址，以便下次评论时使用。 Previous 1,3-Benzenedicarboxylic acid, 5-(2H-tetrazol-5-yl)- Next 5-Chlorothiazole-2-carboxylic acid Easy CDMO Easy CDMO is China TOP100 CDMO company. We believe: Easy CDMO, Medicinal Chemical is Big. More than 100 scientists are serving you. Quick Links About Us Products Blog Contacts Support Links Privacy Policy Term And Condition Locations Office address: Chenxun Technology Building, No. 633, Jinzhong Road, Changning District, Shanghai info@easycdmo.com +8602161734564 © Copyright Easy CDMO 2025. All Rights Reserved.