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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 204196-80-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 204196-80-5 |
Formula : | C8H6N4O2 |
M.W : | 190.16 |
SMILES Code : | OC(=O)C1=CC(=CC=C1)N1C=NN=N1 |
MDL No. : | MFCD00574247 |
InChI Key : | UNTMKIYQHROFCP-UHFFFAOYSA-N |
Pubchem ID : | 750220 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H228 |
Precautionary Statements: | P501-P270-P240-P210-P241-P264-P280-P370+P378-P301+P312+P330 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅲ |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 11 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
80.9 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.86 |
Solubility | 2.63 mg/ml ; 0.0138 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.89 |
Solubility | 2.43 mg/ml ; 0.0128 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.56 |
Solubility | 5.26 mg/ml ; 0.0277 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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 |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.02 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.76 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; | Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound. | |
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; | Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound. | |
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; | Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound. |
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; | Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extracts with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound. | |
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; | Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With MgCl2; triethylamine; In acetonitrile; | Example M15 3-Oxo-3-(3-tetrazol-1-yl-phenyl)-propionic acid ethyl ester Prepared from <strong>[204196-80-5]3-tetrazol-1-yl-benzoic acid</strong> [CAS-No. 204196-80-5] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with Et3N and MgCl2 in CH3CN according to general procedure M (method a). Obtained as a light yellow solid (211 mg). MS (EI) 260 (M+). | |
With MgCl2; triethylamine; In acetonitrile; | Example H15 3-Oxo-3-(3-tetrazol-1-yl-phenyl)-propionic Acid Ethyl Ester Prepared from <strong>[204196-80-5]3-tetrazol-1-yl-benzoic acid</strong> [CAS-No. 204196-80-5] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with Et3N and MgCl2 in CH3CN according to general procedure H (method a). Obtained as a light yellow solid (211 mg). MS (EI) 260 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.1 Synthesis of 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine Prepare by the method of Example 56.1 using <strong>[204196-80-5]3-(1H-tetrazol-1-yl)benzoic acid</strong> and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.1 Synthesis of 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine Prepare by the method of Example 59.1 using <strong>[204196-80-5]3-(1H-tetrazol-1-yl)benzoic acid</strong> and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 80℃; | Thionyl chloride (477 mL, 6.58 mmol) and 3-(lH-tetrazol-l-yl)benzoic acid. (50 mg, 0.263 mmol) was heated to 80 C in a screw-cap vial. After a clear solution was observed, the residue solid on the wall was washed by gentle shaking. After 1.5 h, the reaction was cooled to room temperature. The reaction mixture was concentrated to dryness under reduced pressure. The resulting white solid was suspended in CH2Cl2 (1.5 mL) and treated with p-bromoaniline (90 mg, 0.526 mmol) and triethylamine (100 mL, 0.719 mmol). The reaction was stirred at room temperature for 14 h, mixed with silica gel and concentrated to dryness. Chromatography [silica, CH2Cl2:methanol (98:2 to 1 :3)] yielded an off-white solid (48 mg, 53%). Decomp point 203 C. 1H NMR (300 MHz, DMSO-d6) d 7.58 (d, J= 4.9, 2H), 7.79 (d, J= 4.9, 2H), 7.85 (6, J= 8.0, 1H), 8.10-8.18 (m, 2H), 8.47-8.51 (m, 1H), 10.22 (s, 1H), 10.62 (br, 1H, NH). 13C NMR (75 mHz, DMSO-d6) delta 120.18, 122.08, 123.92, 128.50, 130.11, 131.30, 142.25. ESI-MS Calculated for C14H10BrN5O 344.0141; found 344.0152. | |
With thionyl chloride; N,N-dimethyl-formamide; for 3.0h;Reflux; | General procedure: To the solution of carboxylic acid (1eq.) in thionyl chloride were added one drop DMF. The mixture was heated to reflux temperature and stirred for 3 h. The solvent was removed and the crude material dissolved in DCM. To this solution were added the amine (1eq.) and triethylamine (1.5eq). The mixture was stirred for 3 h at room temperature under argon. Afterwards the DCM was removed. The crude material was dissolved in ethyl acetate and washed with water and brine. The resulting organic layer was dried over MgSO4, and the solvent was removed by evaporation. The obtained residue was purified by flash chromatography (CH2Cl2/MeOH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 4.0h; | General procedure: (S)-2-amino-N-(1-cyanocyclopropyl)-3-(pyridin-3-yl)propanamide (1 Eq.) acid (1 Eq.) and HATU (1.2 Eq.) were dissolved in DMF (0.145 M). DIPEA (4 Eq.) was added dropwise at room temperature and mixture stirred for 4H. The mixture was charged on a Si-CO3 cartridge (2 g) and eluted with MeOH. Volatiles were removed and crude purified by preparative Rp HPLC (MeCN/Water + 0.1% TFA). |
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