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Structure of 1219741-54-4

Chemical Structure| 1219741-54-4

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Product Details of [ 1219741-54-4 ]

CAS No. :1219741-54-4
Formula : C18H21BO3
M.W : 296.17
SMILES Code : OC1=CC=CC=C1C2=CC=C(B3OC(C)(C)C(C)(C)O3)C=C2
MDL No. :MFCD18383811
InChI Key :KHMILAPQGZSSST-UHFFFAOYSA-N
Pubchem ID :59267813

Safety of [ 1219741-54-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 1219741-54-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 12
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 90.38
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

38.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

4.18
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.36
Log Po/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.

2.39
Log Po/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

2.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.58

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-4.58
Solubility 0.00777 mg/ml ; 0.0000262 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.7
Solubility 0.00589 mg/ml ; 0.0000199 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-5.93
Solubility 0.000349 mg/ml ; 0.00000118 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.14 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)

3.11

Application In Synthesis of [ 1219741-54-4 ]

* 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 [ 1219741-54-4 ]

[ 1219741-54-4 ] Synthesis Path-Downstream   1~18

  • 1
  • [ 21849-89-8 ]
  • [ 73183-34-3 ]
  • [ 1219741-54-4 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 150.0℃; for 0.166667h;Microwave irradiation; Step B 4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-2-ol. Potassium acetate (366 mg, 3.73 mmol) and dichloro[1,1'-his (diphenylphosphino) ferrocene]palladium II DCM adduct (25.4 mg, 31 mumol) were added to a solution of 4'-bromobiphenyl-2-ol (310 mg, 1.24 mmol), and bis(pinacolato)diboron (348 mg, 1.37 mmol) in DME (3 mL). The reaction was heated at 150 C. under microwave irradiation for 10 min. Reaction mixture was filtered through a pad of celite and purified by chromatography over silica eluting with 0-50% EtOAc/hexane to furnish the title compound as a white solid.
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 150.0℃; for 0.166667h;Microwave irradiation; Potassium acetate (366 mg, 3.73 mmol) and dichloro [1,1 '-bis (diphenylphosphino) ferrocene] palladium II DCM adduct (25.4 mg, 31 mumol) were added to a solution of 4'-bromobiphenyl-2-ol (310mg, 1.24 mmol), and bis(pinacolato)diboron (348 mg, 1.37 mmol) in DME (3 mL). The reaction was heated at 1500C under microwave irradiation for 10 min. Reaction mixture was filtered through a pad of celite and purified by chromatography over silica eluting with 0-50% EtOAc/hexane to furnish the title compound as a white solid.
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 150.0℃; for 0.166667h;Microwave irradiation; Potassium acetate (366 mg, 3.73 mmol) and dichloro [l,l'-bis (diphenylphosphino) ferrocene] palladium II DCM adduct (25.4 mg, 31 mumol) were added to a solution of 4'-bromobiphenyl-2-ol (310mg, 1.24 mmol), and bis(pinacolato)diboron (348 tug, 1.37 mmol) in DME (3 mL). The reaction was heated at 15O0C under microwave irradiation for 10 min. Reaction mixture was filtered through a pad of Celite and purified by chromatography over silica eluting with 0-50% EtOAc/hexane to furnish the title compound as a white solid.
With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 150.0℃; for 0.166667h;Microwave irradiation; Potassium acetate (366 mg, 3.73 mmol) and dichloro [1,1 '-bis (diphenylphosphino) ferrocene] palladium II DCM adduct (25.4 mg, 31 mumol) were added to a solution of 4'-bromobiphenyl-2-ol (3 lOmg, 1.24 mmol), and bis(pinacolato)diboron (348 mg, 1.37 mmol) in DME (3 mL). The reaction was heated at 1500C under microwave irradiation for 10 min. Reaction mixture was filtered through a pad of Celite and purified by chromatography over silica eluting with 0-50% EtOAc/hexane to furnish the title compound as a white solid.

  • 2
  • [ 1219741-54-4 ]
  • [ 1219741-40-8 ]
  • [ 1219741-75-9 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 140.0℃; for 0.333333h;Microwave irradiation; Step A Methyl 5-[(6-fluoro-5-(2'-hydroxybiphenyl-4-yl)-1-[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate. Potassium phosphate (2 M in water) (270 ul, 0.54 mmol) and Pd(PPh3)4 (6.3 mg, 5.4 mumol) were added to a solution of Intermediate 11B (100 mg, 0.18 mmol), and Intermediate 38 (80 mg, 0.27 mmol) in dioxane (2 mL). The reaction was heated at 140 C. under microwave irradiation for 20 min, then filtered through a membrane syringe filter and concentrated. The residue was re-dissolved in 2 mL methanol, filtered and purified by HPLC eluting with 20-80% MeCN:water to afford the desired product as a white solid.
  • 3
  • [ 1219741-54-4 ]
  • [ 1224724-37-1 ]
  • [ 1224841-17-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80.0℃; for 15.0h; A solution of potassium carbonate (1 M solution in water, 0.15 mL, 0.15 mmol), Pd(PPh3^ (3 mg, 0.0002 mmol), 41-(4,4,5,5-tetramethyl-l,3^-dioxaborolan-2-yl)biphenyl-2-ol (15 mg, 0.05 mmol) and Intermediate 4 (21 mg, 0.05 mmol) in dioxane (0.25 mL) was heated at 80C for 15 h. The aqueous phase was removed and the organic phase was concentrated, diluted with EtOAc, filtered and concentrated to afford the desired product as a solid, which was used in the next step without further purification.
  • 5
  • [ 1219741-54-4 ]
  • [ 1467059-91-1 ]
  • [ 1467061-11-5 ]
YieldReaction ConditionsOperation in experiment
73% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran; ethanol; toluene; at 115.0℃; for 2.0h;Inert atmosphere; A glass tube was charged with <strong>[1219741-54-4]4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-ol</strong> (86.2 mg, 0.29 mmol), methyl 5-bromo-6-chloro-1H-indole-3-carboxylate (84 mg, 0.29 mmol), toluene (1.2 mL), THF (0.6 mL), EtOH (0.6 mL), and 2.0 M potassium carbonate solution (0.6 mL, 1.2 mmol). Nitrogen was then bubbled through the mixture for 5 minutes then [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (28 mg, 0.032 mmol) was added. The tube was sealed and heated to 115 C. for 2 hours. The reaction was cooled to room temperature, opened, and neutralized with 1.0 M sodium hydrogensulfate then diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate (x2). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash column chromatography (20% to 100% ethyl acetate/heptane) was then used to to provide the title compound as a white solid (80 mg, 73% yield). MS (ES-) 376.1 (M-H). 1H NMR (500 MHz, DMSO-d6) delta 12.09 (br. s., 1H), 9.60 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.68 (s, 1H), 7.65 (d, 2H), 7.47 (d, 2H), 7.34 (dd, 1H), 7.19 (dt, 1H), 6.98 (d, 1H), 6.91 (dt, 1H), 3.81 (s, 3H).
  • 6
  • [ 1219741-54-4 ]
  • [ 1467059-91-1 ]
  • [ 1467058-65-6 ]
  • 7
  • [ 1219741-54-4 ]
  • [ 1467058-99-6 ]
  • 8
  • [ 1219741-54-4 ]
  • methyl 6-bromo-5-iodo-1H-indole-3-carboxylate [ No CAS ]
  • [ 1467061-12-6 ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In ethanol; water; toluene; at 110.0℃;Inert atmosphere; Sealed tube; To a solution of methyl 6-bromo-5-iodo-1H-indole-3-carboxylate (100 mg, 0.26 mmol) in toluene (1 ml) and ethanol (1 ml) was added <strong>[1219741-54-4]4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-2-ol</strong> (70 mg, 0.24 mmol) followed by aqueous potassium carbonate (2 M, 1 ml, 2.0 mmol). The solvent was degassed by passing nitrogen through the system for 5 min. Pd(dppf)Cl2 (10 mg, 0.0053 mmol) was added then sealed and reaction heated to 110 C. The reaction was cooled then partitioned between water and ethyl acetate, then washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo to afford the title compound mixed with unidentified byproducts as a dark tan solid (120 mg). TLC (50% EtOAc/Heptane) indicates no separation between product and byproducts. Crude was taken on to the next step without purification.
  • 9
  • [ 1219741-54-4 ]
  • [ 126-30-7 ]
  • [ 1467061-56-8 ]
YieldReaction ConditionsOperation in experiment
99% In 1,4-dioxane; at 210.0℃; for 1.0h;Microwave irradiation; A mixture of 2,2-dimethylpropane-1,3-diol (4.0 g, 38 mmol) and 4'-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-ol (1.0 g, 3.4 mmol) in 1,4-dioxane (2 mL) was subjected to microwave irradiation at 210 C. for 1 hour. The cooled reaction mixture was partitioned between water (50 mL) and 1:1 EtOAc/heptane (25 mL:25 mL). The organic layer was washed with water (30 mL) and brine (30 mL), dried over Na2SO4 and concentrated in vacuo to give the title compound (0.95 g, 99% yield). GC/MS, M=282 at 5.31 min. 1H NMR (500 MHz, CDCl3) delta 7.94 (d, J=7.81 Hz, 2H), 7.48 (d, J=7.81 Hz, 2H), 7.31-7.26 (m, 2H), 7.03-6.98 (m, 2H), 3.82 (s, 4H), 1.08-1.04 (m, 6H).
  • 12
  • [ 1219741-54-4 ]
  • [ 117637-79-3 ]
  • ethyl 3-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; ethanol; water; toluene; at 85.0℃;Inert atmosphere; 4?-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl) biphenyl-2-ol (98 mg, 0.33 mmol), Pd(dppf)Cl2 (10 mg, 0.01 mmol) and, lastly, an aqueous solution (5 ml) of K2CO3 (150 mg, 1.08 mmol) are added to a solution of iodised derivative 2 (87 mg, 0.27 mmol) in a solvent mixture of 1,4-dioxane:toluene:ethanol:water 10:1:3:6 (20 ml). The mixture is stirred at 85 C. all night in a nitrogen atmosphere. Once the reaction has concluded, the solvent is evaporated at reduce pressure. The residue is dissolved in water (10 ml) and extracted with AcOEt (3×10 ml). The organic layer is dried over anhydrous sodium sulfate, filtered and evaporated under reduce pressure. The crude obtained is purified by column chromatography (CH2Cl2:MeOH 20:1). 56 mg (60%) are obtained as a beige solid. MS (ES, positive mode): m/z 357 (96%) (M+1)+. 1H NMR (DMSO-d6) delta 11.96 (s, 1H), 9.63 (s, 1H), 8.18-6.05 (m, 12H), 4.30 (d, J=7.1 Hz, 2H), 1.28 (t, J=7.1 Hz, 3H). 13C NMR (DMSO-d6) delta 14.4, 60.7, 113.1, 116.5, 119.9, 120.9, 121.1, 122.8, 123.1, 125.5, 127.2, 127.9, 128.8, 130.4, 130.7, 132.1, 136.6, 137.5, 154.8, 161.7.
  • 13
  • [ 1219741-54-4 ]
  • [ 163630-17-9 ]
  • ethyl 1-benzyl-3-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; ethanol; water; toluene; at 85.0℃; for 3.0h;Inert atmosphere; 4?-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl) biphenyl-2-ol (255 mg, 0.86 mmol), Pd(dppf)Cl2 (26 mg, 0.036 mmol) and, lastly, an aqueous solution (5 ml) of K2CO3 (398 mg, 2.88 mmol) are added to a solution of the iodised benzyl derivative 3 (290 mg, 0.72 mmol) in a solvent mixture of 1,4-dioxane: toluene:ethanol:water 10:1:3:6 (20 ml). The mixture is stirred at 85 C. for 3 hours in a nitrogen atmosphere. Once the reaction has concluded, the solvent is evaporated at reduced pressure. The residue is dissolved in water (10 ml) and extracted with AcOEt (3×10 ml). The organic layer is dried over anhydrous sodium sulfate, filtered and evaporated. The crude is purified by column chromatography (CH2Cl2:MeOH 50:1). 305 mg (95%) are obtained as a beige solid. MS (ES, positive mode): m/z 447 (95%) (M+1)+. 1H NMR (DMSO-d6) delta 9.59 (s, 1H), 8.05-6.45 (m, 17H), 5.79 (s, 2H), 4.12 (q, J=6.5 Hz, 2H), 1.00 (t, J=7.1, 6.5 Hz, 3H). 13C NMR (DMSO-d6) delta 13.8, 47.8, 55.3, 61.0, 111.7, 116.5, 119.9, 121.3, 121.5, 123.8, 125.0, 125.7, 126.2, 126.7, 127.5, 127.8, 128.8, 128.9, 129.0, 130.0, 130.6, 132.3, 137.5, 138.1, 138.7, 154.8, 162.2.
  • 14
  • [ 1219741-19-1 ]
  • [ 1219741-54-4 ]
  • C20H15ClN2O3S [ No CAS ]
  • 15
  • [ 1219741-54-4 ]
  • methyl 5-((6-chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoate [ No CAS ]
  • 16
  • [ 1219741-54-4 ]
  • 3,3-((6-chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-benzo[d]imidazol-2-yl)thio)benzoic acid [ No CAS ]
  • 17
  • [ 1219741-54-4 ]
  • 5-((6-chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-benzo-[d]imidazol-2-yl)oxy)-2-methylbenzoic acid [ No CAS ]
  • 18
  • [ 1219741-54-4 ]
  • methyl 5-((6-chloro-5-iodo-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-methylbenzoate [ No CAS ]
  • methyl 5-((6-chloro-5-(2’-hydroxy-[1,1’-biphenyl]-4-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-methylbenzoate [ No CAS ]
 

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