Structure of 934-22-5
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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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Jang, Mingyeong ; Lim, Taeho ; Park, Byoung Yong ; Han, Min Su ;
Abstract: In this study, we developed a metal-free and highly chemoselective method for the reduction of aromatic nitro compounds. This reduction was performed using tetrahydroxydiboron [B2(OH)4] as the reductant and 4,4'-bipyridine as the organocatalyst and could be completed within 5 min at room temperature. Under optimal conditions, nitroarenes with sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen, were converted into the corresponding anilines with excellent selectivity while avoiding the undesirable reduction of the sensitive functional groups.
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CAS No. : | 934-22-5 |
Formula : | C7H7N3 |
M.W : | 133.15 |
SMILES Code : | NC1=CC=C2C(NC=N2)=C1 |
MDL No. : | MFCD00831692 |
InChI Key : | WFRXSXUDWCVSPI-UHFFFAOYSA-N |
Pubchem ID : | 13623 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H315-H319-H332-H335 |
Precautionary Statements: | P233-P260-P261-P264-P270-P271-P280-P301+P312-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P322-P330-P332+P313-P337+P313-P340-P362-P363-P403-P403+P233-P405-P501 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.7 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.04 |
Solubility | 1.2 mg/ml ; 0.00905 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.87 |
Solubility | 1.79 mg/ml ; 0.0134 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.404 mg/ml ; 0.00303 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 |
Yes |
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) |
Yes |
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 |
-6.31 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 |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 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) |
1.33 |
* 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 |
---|---|---|
8% | Compound 440: 1 -(1 H-Benzoimidazol-5-yl)-5-benzo[c][1 ,2,5]oxadiazol-5-yl-4- cyclopropanecarbonyl-S-hydroxy-I .S-dihydro-pyrrol^-one; 1 H-Benzoimidazol-5-ylamine (1 mmol) and Benzo[1 ,2,5]oxadiazole-5-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 4-Cyclopropyl-2,4-dioxo-butyric acid ethyl ester (1 mmol) was added. The reaction was heated to 500C and stirred for 24h. After evaporation of the solvent the residue was purified with chromatographic methods.molecular weight (g/mol): 401.38 IC50 hQC (nM): 1 1.4Yield: 0.032g (8 percent); mp: 1700C, 1H NMR delta 0.73-0.75 (m, 1 H, CH2), 0.83-0.85 (m, 2 H, CH2), 0.94-0.96 (m, 1 H, CH2), 2.92-2.94 (CH-CH2), 6.37 (s, 1 H, CH-N), 7.40 (dd, 3J=9.5 Hz, 4J=1.2 Hz, 1 H, Ar), 7.64-7.66 (m, 2 H, Ar, Benzimid), 7.83 (d, 3J=9.5 Hz, 1 H, Ar), 8.05 (s, 1 H, Benzimid), 8.18 (s, 1 H, Benzimid), 9.10 (s, 1 H, Benzimid); MS m/z 402.2 (M+H)+, HPLC (254 nm): rt 2.75 min (100 percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Compound 446: 1 -(1 H-Benzoimidazol-S-ylJ^-cyclopropanecarbonyl-S-hydroxy-S-tdelta- hydroxy-quinolin-2-yl)-1 ,5-dihydro-pyrrol-2-one; 1 H-Benzoimidazol-5-ylamine (1 mmol) and 8-Hydroxy-quinoline-2-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 3 4-Cyclopropyl-2,4-dioxo-butyric acid ethyl ester (1 EPO <DP n="188"/>mmol) was added. The reaction was heated to 500C and stirred for 24h. After evaporation of the solvent the residue was purified with chromatographic methods.molecular weight (g/mol): 426.44 IC50 hQC (nM): 1.35Yield: 0.174g (41 percent); mp: 155°C, 1H NMR delta 0.67-0.71 (m, 1 H, CH2), 0.77-0.85 (m, 2 H, CH2), 0.88-0.93 (m, 1 H, CH2), 2.85-2.96 (CH-CH2), 6.39 (s, 1 H, CH-N), 6.99 (dd, 3J=6.4 Hz, 4J=1.2 Hz, 1 H, Ar), 7.22 (dd, 3J=7.0 Hz, 4J=1.2 Hz, 1 H, Ar), 7.31 (t, 3J=7.8 Hz, 1 H, Ar), 7.51 (d, 3J=8.6 Hz, 1 H, Ar), 7.60 (d, 3J=9.0 Hz, 1 H, Benzimid), 7.75 (dd, 3J=9.0 Hz, 4J=1.9 Hz, 1 H, Ar), 8.09-8.1 1 (m, 2 H, Benzimid), 9.03 (s, 1 H, Benzimid), 9.53 (s, br., 1 H, NH); MS m/z 427.0 (M+H)+, HPLC (254 nm): rt 2.81 min (100 percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | Compound 287: 1 -(1 H-Benzoimidazol-5-yl)-5-benzo[c][1 ,2,5]thiadiazol-5-yl-4- cyclopropanecarbonyl-S-hydroxy-I .S-dihydro-pyrrol^-one; 1 H-Benzoimidazol-5-ylamine (1 mmol) and Benzo[1 ,2,5]thiadiazole-5-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 4-Cyclopropyl-2,4-dioxo-butyric acid ethyl ester (1 mmol) was added. The reaction was heated to 500C and stirred for 24h. After evaporation of the solvent the residue was purified with chromatographic methods.molecular weight (g/mol): 417.45 IC50 hQC (nM): 0.7Yield: 0.05 g (16 percent); mp: 270.000C, decomposed, 1H NMR delta 1 H-NMR (500 MHz, DMSO-D6): 0.66-0.71 (m, 1 H, CH2), 0.77-0.84 (m, 2 H, CH2), 0.89-0.95 (m, 1 H, CH2), 2.91-2.95 (CH-CH2), 6.36 (s, 1 H, CH-N), 7.45-7.50 (m, 3 H, Ar), 7.85-7.87 (m, 2 H, Benzimid), 8.12 (d, 4J=0.9 Hz, 1 H, Benzimid), 9.03 (s, 1 H, Benzimid). MS m/z 418.4 (M+H)+, HPLC (254 nm): rt 2.74 min (100 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.1% | The respective 2-oxo benzoic acid (1 eq.) was dissolved in THF (5 ml in case of 1 mmol) and DCC (1 eq.) was added. After stirring at r.t. for 1 h, benzimidazol-5(6)-amine (1 eq.) was added and stirring at r.t. was continued for 24 h. The mixture was put into the fridge for 2 h and afterwards the precipitated solid was filtered off. The filtrate was concentrated in vacuo, re-dissolved in a mixture of AcOH and toluol (3 ml and 7 ml in case of 1 mmol batch) and refluxed over night. After cooling the solvents were evaporated. The resulting residue was dissolved in CH2Cl2 (10 ml in case of 1 mmol batch), cooled to 0 C. and treated with TFA (1 ml (4 ml) per mmol). After stirring at r.t. for 10 min, triethylsilane (2 eq. (4 eq.)) was added. The reaction was allowed to warm up to room temperature and stirred for 3 h. After that time, the mixture was quenched with saturated sodium bicarbonate solution. The organic layer was separated and the aqueous layer was extracted with EtOAc (3×25 ml). The combined organic layers were dried over Na2SO4, concentrated in vacuo and the remaining residue was purified by flash-chromatography using silica gel and a CHCl3/MeOH gradient. Example 1262-(1H-benzo[d]imidazol-5-yl)-3-(4-biphenyl)isoindolin-1-oneThe compound was synthesized according to method 11.2-(4-Phenylbenzoyl)benzoic acid (1.0 g; 3.3 mmol), DCC (680 mg; 3.3 mmol), benzimidazol-5(6)-amine (440 mg; 3.3 mmol), TFA (3.92 ml) and triethylsilane (0.624 ml; 3.92 mmol; 4 eq.) and was additional purified by semi-preparative HPLC; yield: 0.120 g (9.1%); MS m/z: 402.1 [M+H]+; 1H-NMR (DMSO d6, 400 MHz): delta 6.79 (s, 1H); 7.28-7.32 (m, 1H); 7.36-7.40 (m, 5H); 7.53-7.60 (m, 5H); 7.63-7.66 (m, 1H); 7.72-7.74 (d, 1H, 3J=8.7 Hz); 7.76-7.79 (dd, 1H, 4J=1.7 Hz, 3J=8.7 Hz); 7.89-7.91 (m, 1H); 8.17-8.18 (d, 1H, 4J=1.7 Hz); 9.06 (s, 1H); HPLC (Gradient 3): rt 15.20 min (97.0%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.045 g (15.4%) | With potassium carbonate; | Example 40 N-(2,5-Dichlorobenzyl)-1H-benzo[d]imidazol-5-amine The compound was synthesized starting from benzimidazol-5-amine (133 mg; 1 mmol; 1 eq.), <strong>[85482-13-9]2,5-dichlorobenzylbromide</strong> (528 mg; 2.2 mmol; 2.2 eq.) and K2CO3 (304 mg; 2.2 mmol; 2.2 eq.) according to method 5. Yield: 0.045 g (15.4%); MS m/z: 292.2/294.3 [M+H]+; 1H-NMR (500 MHz, DMSO d6): delta 4.32 (d, 2H, 3J=6.1 Hz); 6.20 (br s, 1H); 6.43 (br s, 1H); 6.60 (dd, 1H, 4J=1.6 Hz, 3J=8.8 Hz); 7.30-7.33 (m, 2H); 7.40 (d, 1H, 4J=2.6 Hz); 7.49 (d, 1H, 3J=8.5 Hz); 7.86 (s, 1H), 11.83 (br s, 1H); HPLC (METHOD [A]): rt 12.97 min (100%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A solution of 1H-benzo[d]imidazol-5-amine (1 eq.) and the respective aldehyde (1 eq.) in dry methanol (1-3 ml per mmol) was stirred at room temperature for 3 hours. After addition of mono-tert-Butyl malonate (1 eq.) and 1-isocyano-2-methylpropan-2-yl methyl carbonate (1 eq.) stirring was continued for 48 hours. The solvent was evaporated and the residue was purified by flash chromatography on silica gel using a CHCl3/MeOH gradient. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14 mg | Example 297: Preparation of N2-(lH-benzo[d]imidazol-6-yl)-N4-(5-cyclobutyl-lH-pyrazol- 3-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine2,4-Dichloro-5-(trifluoromethyl)pyrimidine (0.087 g, 0.401 mmol), 5-cyclobutyl-lH- pyrazol-3-amine (0.055 g, 0.401 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.077 ml,0.441 mmol) were mixed in acetonitrile (2 ml). The mixture was microwaved at 80 C for 20 min and then concentrated. lH-benzo[d]imidazol-6-amine (0.053 g, 0.401 mmol) and acetic acid (0.024 g, 0.401 mmol) were added. The mixture was microwaved at 110 C for 20 min and then concentrated. 14 mg of product was recovered after automated reverse phase chromatography (water-MeCN). MS calcd for [Ci9Hi7F3N8+H]+: 415.16, found 415.20. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; at 120℃; | To a solution of compound 23 (0.60 g, 2.51 mmol, 1.00 eq) in AcOH (10.0 mL) was added compound 1A (594 mg, 3.76 mmol, 531 mL, 1.50 eq) and compound 1B (500 mg, 3.76 mmol, 1.50 eq). The mixture was stirred at 120 C for 12 hours. LCMS showed compound 23 was consumed and a main peak with the desired mass was detected. The mixture was concentrated under vacuum to give the crude product which was purified by reversed-phase C18 column chromatography (0.1% formic acid, 0-25% MeCN in water) to give compound 23_1 (0.10 g, 90.7 mmol, 3.62% yield, 42.3% purity) as a brown solid. LCMS: product RT = 0.858 min, m/z = 467.0 (M+1)+. |
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