Structure of 155600-99-0
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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. : | 155600-99-0 |
Formula : | C4H3Br2N3O2 |
M.W : | 284.89 |
SMILES Code : | O=[N+](C1=C(Br)N(C)N=C1Br)[O-] |
MDL No. : | MFCD09972218 |
InChI Key : | PGMQVDHYFOWDLI-UHFFFAOYSA-N |
Pubchem ID : | 22918638 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.64 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.45 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.21 |
Solubility | 0.177 mg/ml ; 0.000622 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.08 |
Solubility | 0.239 mg/ml ; 0.000837 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.88 |
Solubility | 3.78 mg/ml ; 0.0133 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 |
-6.54 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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.11 |
* 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 |
---|---|---|
Production example 1 3,5-dibromo-1-methyl-4-nitropyrazole In method II using methyl sulfate, 5.06 g (96 percent of theory) of 3,5-dibromo-1-methyl-4-nitropyrazole are obtained in the form of white crystals with a melting point of 154 C. 1 H-NMR (60 MHz, DMSO-d6):=3.90 ppm (s; 3H; --CH3). In this and in all of the following 1 H-NMR spectra: chemical shift is indicated in delta (ppm), the coupling constants (J) are indicated in Hertz. Standard: tetramethylsilane s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, Ph=phenyl, ring-H=proton on pyrazole ring MS (70 eV): m/e=287 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; | Production example 9 5-benzylamino-3-bromo-1-methyl-4-nitropyrazole 2 g (7.02 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 11 g (0.1 mole) of benzylamine in 50 ml ethanol for 10 hours at boiling temperature. After cooling, the reaction mixture is poured on 100 ml water, the separated product is filtered and washed with water (20 ml). After vacuum drying, 1.76 g (81 percent of theory) of 5-benzylamino-3-bromo-1-methyl-4-nitropyrazole are obtained in the form of yellow needles with a melting point of 133 C. 1 H-NMR (60 MHz, DMSO-d6):=7.88 (t; 1H; J=6 Hz; --NH; exchangeable with D2 O), 7.32 (m; 5H; Ph-H), 4,73 (d; 2H; J=6 Hz; --NH--CH2 --; s after exchanging with D2 O) and 3.68 ppm (s; 3H; N--CH3). MS (70 eV): m/e=312 (M+). | |
In dimethyl sulfoxide; | Nucleophilic aromatic substitution of the compound 2 with benzylamine in DMSO produces benzyl-(5-bromo-2-methyl-4-nitro-2H-pyrazol-3-yl)-amine 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methylamine; In ethanol; water; | Production example 6 3-bromo-1-methyl-5-methylamino-4-nitropyrazole 2 g (7.02 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in 50 ml of a 40-percent solution of methylamine in ethanol for 4 hours at boiling temperature. After cooling, 100 ml water are added to the reaction mixture, the separated product is filtered out and washed with a small amount of water (20 ml). After vacuum drying, 1.45 g (88 percent of theory) of 3-bromo-1-methyl-5-methylamino-4-nitropyrazole are obtained in the form of yellow crystals with a melting point of 185 C. 1 H-NMR (60 MHz, DMSO-d6):=7.50 (s; wide; 1H; --NH; exchangeable with D2 O), 3.88 (s; 3H; N--CH3) and 3.16 ppm (d; 3H; J=6 Hz; --NH--CH3; s after exchanging with D2 O). MS (70 eV):m/e=236 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tert-butylamine; In ethanol; water; | Production example 8 3-bromo-5-tert-butylamino-1-methyl-4-nitropyrazole 1.5 g (5.26 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 20 ml tert-butylamine in 30 ml ethanol for 20 hours at boiling temperature. After cooling, the reaction mixture is poured on 150 ml water, the separated product is filtered and washed with 100 ml water. After vacuum drying, 1.14 g (78 percent of theory) of 3-bromo-5-tert-butylamino-1-methyl-4-nitropyrazole are obtained in the form of pale yellow flakes with a melting point of 75 to 77 C. 1 H-NMR (60 MHz, DMSO-d6):=5.35 (s; 1H; --NH; exchanges with D2 O), 3.75 (s; 3H; N--CH3) and 1.20 ppm (s; 9H; --C(CH3)3). MS (70 eV): m/e=277 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; | Production example 7 3-bromo-5-(2'-hydroxyethylamino)-1-methyl-4-nitropyrazole 3 g (10.5 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 30 ml ethanolamine in 30 ml ethanol for 15 hours at boiling temperature. The reaction mixture is then poured on 200 ml water, the separated product is filtered, washed with water (20 ml) and vacuum dried. Additional product crystallizes from the filtrate when cooled (5 C.). 2.25 g (81 percent of theory) of 3-bromo-5-(2'-hydroxyethyl)amino-1-methyl-4-nitropyrazole are obtained in the form of yellow crystals with a melting point of 150 C. 1 H-NMR (60 MHz, DMSO-d6): =7.38 (s; wide; 1H; --NH; exchangeable with D2 O), 4.98 (s; wide; 1H; --OH; exchangeable with D2 O), 3.82 (s; 3H; N--CH3) and 3.60 ppm (m; 4H; --NH --CH2 --CH2). MS (70 eV):m/e=266 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; | Nucleophilic aromatic substitution of the compound 2 with benzylamine in DMSO produces benzyl-(5-bromo-2-propyl-4-nitro-2H-pyrazol-3-yl)-amine 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Preparation of N-benzyl-3-bromo-1-methyl-4-nitro-1H-pyrazol-5-amine (3) 3,5-dibromo-1-methyl-4-nitropyzole 2 (2.85 g 10 mmol) was heated in a solution of 10 mL of benzylamine for 6 h at 80 C. After cooling to room temperature, the reaction mixture was poured into water and the yellow solid formed. Then it was filtered, washed with water, dried and recrystallized from toluene to afford 3 g of 3 in yield of 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.6% | With CH3I; In N,N-dimethyl-formamide; | Example A 4,5-Diamino-1-methyl-1H-pyrazole-3-carbonitrile, obtainable from the following synthesis strategy: Preparation of 3,5-dibromo-1-methyl-4-nitro-1H-pyrazole (2): To a solution of 3,5-dibromo-4-nitropyrazole 1 (0.934 g, 3.45 mmol) in 5 mL of absolute DMF were added dropwise 0.16 g of sodium hydride (6.67 mmol) in DMF (100 mL) over a period of 1 h. After cessation of gas generation, 0.26 mL of CH3I (3.89 mmole) was added dropwise and stirred at room temperature for overnight. The solvent was then evaporated under vacuum and the residue was poured into water, The separated solid was filtered, washed with water and dried under vacuum to afford 0.713 g of 2 (yield 72.6%). |
With NaH; methyl iodide; In N,N-dimethyl-formamide; | Example F 1-Methyl-3-phenoxy-1H-pyrazole-4,5-diamine, obtainable from the following synthetic strategy: Treatment of 3,5-dibromo-4-nitro-1H-pyrazole 1 with MeI and NaH in DMF affords 3,5-dibromo-1-methyl-4-nitro-1H-pyrazole 2. |
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