Structure of 124004-31-5
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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. : | 124004-31-5 |
Formula : | C4H5N3O2 |
M.W : | 127.10 |
SMILES Code : | NC1=CC(=NN1)C(O)=O |
MDL No. : | MFCD01528030 |
InChI Key : | ICASMSGEUGPHGI-UHFFFAOYSA-N |
Pubchem ID : | 543072 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 29.95 |
TPSA ? Topological Polar Surface Area: Calculated from |
92.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-0.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.3 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.42 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.8 |
Solubility | 20.0 mg/ml ; 0.157 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.2 |
Solubility | 7.96 mg/ml ; 0.0627 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.21 |
Solubility | 78.6 mg/ml ; 0.618 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 |
-7.27 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 |
2.0 |
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) |
1.65 |
* 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 |
---|---|---|
71% | In acetic acid; | 5.1 Preparation of 5-pyridin-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid 4,4,4-Trifluoro-1-pyridin-2-yl-butane-1,3-dione (3.00 g, 13.8 mmol) and <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (1.76 g, 13.8 mmol) in acetic acid (100 ml) was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure and the crude product was purified by column chromatography on silica gel to give 5-pyridin-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (3.04 g, 71%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In acetic acid; | 5.2 Preparation of 5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid 1-(3,4-Dichloro-phenyl)-4,4,4-trifluoro-butane-1,3-dione (1.00 g, 3.51 mmol) and <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (0.446 g, 3.51 mmoL) in acetic acid (100 mL) was heated at reflux for 48 hours. The reaction concentrated under reduced pressure and the crude product was purified by column chromatography on silica gel to give 5-(3,4-dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (1.20 g, 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | In pyridine; | 5.3 Preparation of 7-amino-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid 3-(3,4-Dichloro-phenyl)-3-oxo-propionitrile (1.00 g, 4.67 mmol) and <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (0.593 g, 4.67 mmol) in pyridine (50 mL) was heated at reflux for 3 days. The reaction was concentrated under reduced pressure and the crude product was purified by column chromatography on silica gel to give 7-amino-5-(3,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (0.125 g, 8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V); In dichloromethane; for 16h; | Step 1 : To slurry of 5-amino-lH-pyrazole-3-carboxylic acid (0.318 g, 2.5 mmol), tert-butyl 3-aminopropylcarbamate (0.479 g, 2.75 mmol) and Hunig'sBase (2.183 mL, 12.50 mmol) in CH2C12 (8 mL) was added PyBOP (1.561 g, 3.00 mmol) and tin- resulting solution was stirred for 16 h. After concentration, the residue was purified by Biotage eluting with 5%-20% MeOH in CH2C12 to give 700 mg of a crude product that will be used as it is in the next step. MS m/z (M+H) + 284.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With acetic acid; at 120℃; for 4h;Sealed tube; | To a solution of <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (600 mg, 4.7 mmol, 1 eq) in acetic acid (30 mL) was added 2-ethoxymethylene-malonic acid diethyl ester (1.1 g, 5.2 mmol, 1.1 eq). The mixture was heated at 120 C. for 4 h in a sealed tube. After cooling, the precipitate was filtered and washed with ethanol to afford the expected compound as grey powder (353 mg, 30% yield). |
30% | With acetic acid; at 120℃; for 4h;Sealed tube; | To a solution of <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (600 mg, 4.7 mmol, 1 eq) in acetic acid (30 mL) was added 2-ethoxymethylene-malonic acid diethyl ester (1.1 g, 5.2 mmol, 1.1 eq). The mixture was heated at 120 C. for 4 h in a sealed tube. After cooling, the precipitate was filtered and washed with ethanol to afford the expected compound as grey powder (353 mg, 30% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | In ethanol; at 80℃; for 20h; | (0180) A mixture of methyl 3-(3-((dimethylamino)methylene)-4-oxopiperidin-1-yl)benzoate (0.606 g, 2.10 mmol) and <strong>[124004-31-5]5-amino-1H-pyrazole-3-carboxylic acid</strong> (0.404 g, 3.18 mmol) in EtOH (8.0 mL) was stirred at 80 C. for 20 h. The mixture was cooled and concentrated. The residue was taken up in H2O and acidified to pH=2 with 1N HCl. The precipitate was filtered off and washed with water, MTBE and hexanes. Dried under high vacuum to afford the title compound (0.362 g, 49%) as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Preparation 13 5-Amino-1H-pyrazole-3-carboxylic acid To a mixture of 3-nitro-1H-pyrazole-5-carboxylic acid (0.50 g, 3.18 mmol) in EtOAc/MeOH (3:1, 10.0 mL) was added a solution of Pearlman's Catalyst (Wet PdOH/C, 20%; 0.050 g) and Degussa Catalyst (Wet PdOH/C, 20%, En101 NE/W; 0.050 g) in EtOAc (2.0 mL). The mixture was stirred under an atmosphere of H2 at room temp. for 20 h. The mixture was purged with N2. A 1N NaOH (3.2 mL) solution was added and the mixture stirred at room temp. for 30 minutes. The mixture was filtered over celite, washing with EtOAc and MeOH. The filtrate was concentrated then acidified to pH=2 with 1N HCl to afford the title compound (0.404 g, quantitative) as a lavender solid. The solid was filtered off, washed with water and dried under high vacuum. No further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; acetic acid; at 25 - 140℃; for 22h; | Compounds 5 and 3 were dissolved in a solution of HCI and AcOH and reacted at 140C under reflux for 6 h, and subsequently at 25C for 16h. During that time, an orange solid was formed and after the end of the reaction, the solid was removed by filtration. Subsequently, the solid was washed with ice-cold water, and then with EtOAc/Toluene 1 :1 . The filtrate was collected and the solvent was removed by rotary evaporation to obtain compound D1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With iron(III) chloride hexahydrate; pyrographite; hydrazine hydrate; In water; for 30h;Reflux; | General procedure: Reduction of the nitrogroup was carried out according to a published method.21The corresponding nitro acid 1, 3 (0.032 mol) wassuspended in H2O (30 ml). Activated carbon (0.8 g),N2H4·H2O (95%, rho 1.023 g/cm3) (6.55 ml, 6.71 g, 0.134 mol),and FeCl3·6H2O (64 mg) were added to the suspension withstirring. The reaction mixture was heated under reflux for30 h. The hot solution was filtered, the filtrate wasevaporated to dryness under reduced pressure. Theresulting dry residue was dissolved in H2O (20 ml) andcarefully acidified with 2 M aqueous HCl to pH 4-5. Theformed precipitate was filtered off and washed with a smallamount of H2O. The product was dried in a vacuumdesiccator over P2O5 to constant weight.5-Amino-1-pyrazole-3-carboxylic acid (2). Yield3.25 g (80%), colorless solid, mp 245-246. 1H NMRspectrum (400 MHz, DMSO-d6), delta, ppm: 5.77 (1H, s, -4pyrazole). 13C NMR spectrum (126 MHz, DMSO-d6),delta, ppm: 162.2; 152.8; 138.3; 92.3. 1H NMR spectrum andmp of the obtained compound correspond to the publisheddata.23 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | General procedure: The corresponding amino acid2, 4 (0.0173 mol) was dissolved in 2 aqueous l (50 ml),and the formed solution was cooled to 0 in an ice bath.Aqueous NaNO2 (0.019 mol) was dropwise added to thereaction mixture. The mixture was stirred for 30 min, thenaqueous NaN3 (0.026 mol) was carefully added. Thereaction mixture was stirred for 3-4 h. The formed precipitatewas filtered off on a fritted glass filter and washed witha small amount of H2O, then dried in a vacuum desiccatorover P2O5 to constant weight. The filtrate was extractedwith EtOAc, the organic phase was separated and driedover anhydrous Na2SO4. The dried organic phase wasevaporated under reduced pressure on the rotary evaporatorto afford a solid. Both solids were combined.5-Azido-1-pyrazole-3-carboxylic acid (5). Yield 2.32 g(87%), yellow solid, mp 164-165. IR spectrum, nu, cm-1:3309 (NH), 3101 (OH), 2125 (N3), 1675 (C=O). 1H NMRspectrum (400 MHz, DMSO-d6), delta, ppm: 13.76 (2, br. s,NH, COOH); 6.48 (1H, s, -4 pyrazole). 13C NMRspectrum (101 MHz, DMSO-d6), delta, ppm: 160.3; 147.6;136.9; 98.9. Found, m/z: 154.0363 [M+H]+. C4H4N5O2.Calculated, m/z: 154.0360. Found, %: C 31.51; H 1.82;N 45.37. 4H3N5O2. Calculated, %: C 31.38; H 1.98;N 45.74. |