Structure of 754219-01-7
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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. : | 754219-01-7 |
Formula : | C7H9IN2O2 |
M.W : | 280.06 |
SMILES Code : | O=C(C1=C(I)N(C)N=C1)OCC |
MDL No. : | MFCD21362331 |
InChI Key : | IGTMQHLEJKSRLJ-UHFFFAOYSA-N |
Pubchem ID : | 57681171 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.4 |
Solubility | 1.1 mg/ml ; 0.00394 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.66 |
Solubility | 6.12 mg/ml ; 0.0218 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.23 |
Solubility | 1.66 mg/ml ; 0.00594 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 |
-7.2 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.24 |
* 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 water; | On the other hand, 5-iodo-1-methylpyrazole-4-carboxylic acid (150 mg, 0.58 mmol), given by hydrolysis of <strong>[754219-01-7]5-iodo-1-methylpyrazole-4-carboxylic acid ethyl ester</strong> (Reference compound No.15-2), and oxalyl chloride (0.053 mL, 0.61 mmol) were stirred at 50C for 1 hour. N,N-Diisopropylethylamine (0.51 mL, 2.9 mmol) and amine-derivative polystyrene(I) were added to a solution of 5-iodo-1-methylpyrazole-4-carbonyl chloride prepared by an above method in anhydrous methylene chloride (3.3 mL), and then the whole was shaken at room temperature for 19 hours. The reaction mixture was filtered, the polystyrene resin was washed with methanol (6.0 mL) and chloroform (6.0 mL) four times alternately, and then the resin was washed with diethyl ether (6.0 mL), and dried under reduced pressure to give amide-derivative polystyrene (II). This resin(II), tris(dibenzylideneacetone)dipalladium(0) (160 mg, 0.17 mmol), 1,1-bis(diphenylphosphino)ferrocene (400 mg, 0.73 mmol), and N,N-diisopropylethylamine (0.60 mL, 3.3 mmol) were suspended in N,N-dimethylacetamide (5.0 mL). This suspension was frozen, allowed to stand under reduced pressure, and melted. This procedure was repeated twice and dissolved oxygen in the solvent was removed, 4-pyridinemethanethiol hydrochloride (0.40 g, 2.70 mmol) was added thereto, and then the reaction mixture was stirred at 60 C under an argon atmosphere for 24 hours. The reaction mixture was filtered, the resulting resin was washed with N,N-dimethylformamide (6.0 mL) twice, with methanol (6.0 mL) and chloroform (6.0 mL) three times alternately, and with diethyl ether (6.0 mL), then dried under reduced pressure. A solution of 20% trifluoroacetic acid in methylene chloride (5.0 mL) was added to this resin, the whole was shaken at room temperature for 30 minutes, and then polystylene resin was filtered out. The filtrate was diluted with methylene chloride (4.0 mL), and then a saturated aqueous sodium hydrogencarbonate solution was added to adjust to pH 7. The methylene chloride layer was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography to give 7.0 mg of the title compound as a yellow solid. (Yield 36%)1H-NMR(500MHz,CDCl3)delta 2.33(s,6H),3.59(s,3H),3.97(s,2H),6.80(s,1H),6.94(dd,J = 4.4,1.6 Hz,2H), 7.22(s,2H),8.11(s,1H),8.48(dd,J = 4.4,1.6 Hz,2H),8.81(s,1H) | |
With water; lithium hydroxide; In tetrahydrofuran; at 25℃; for 15.0h; | A mixture of ethyl 5-iodo-1-methyl-pyrazole-4-carboxylate (7.5 g, 26.8 mmol) and lithium hydroxide (6.4 g, 268.0 mmol) in tetrahydrofuran (100 mL) and water (100 mL) was stirred at 25 C. for 15 h and concentrated under reduced pressure. The residue was adjusted to pH=5 by additional of hydrochloric acid (2 N). The formed solid was collected by filtration, washed with water (20 mL) and dried in vacuo to afford crude 5-iodo-1-methyl-1H-pyrazole-4-carboxylic acid (6.0 g, 89%) as a white solid, used as is in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42%; 42% | With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 15.0h; | A mixture of ethyl 3-iodo-1H-pyrazole-4-carboxylate (17.0 g, 63.9 mmol), cesium carbonate (41.6 g, 127.8 mmol) and methyl iodide (6.0 mL, 95.9 mmol) in N,N-dimethylformamide (200 mL) was heated at 60 C. for 15 h and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh, 0 to 20% ethyl acetate in petroleum ether) to give ethyl 3-iodo-1-methyl-pyrazole-4-carboxylate (7.5 g, 42%) as a white solid and ethyl 5-iodo-1-methyl-pyrazole-4-carboxylate (7.5 g, 42%) as a white solid, used as is in the next step. |
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