Structure of 39806-90-1
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 39806-90-1 |
Formula : | C4H5IN2 |
M.W : | 208.00 |
SMILES Code : | CN1N=CC(I)=C1 |
MDL No. : | MFCD05663860 |
InChI Key : | RSDRDHPLXWMTRJ-UHFFFAOYSA-N |
Pubchem ID : | 2734773 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.62 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.99 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.27 mg/ml ; 0.00613 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.84 |
Solubility | 30.2 mg/ml ; 0.145 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.75 |
Solubility | 3.67 mg/ml ; 0.0177 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) |
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 |
-6.94 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) |
1.65 |
* 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 |
---|---|---|
2.4 g | With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; sodium carbonate; In butan-1-ol; for 4h;Inert atmosphere; Reflux; | General procedure: Step 2: 1-[(1-methyl)-4-pyrazolyl]ethanone 1-methyl-4-iodopyrazole (10 g), vinyl-n-butyl ether (24 g), palladium acetate (396 mg), 1,3-bi(diphenyl phosphine)propane (988 mg), sodium carbonate (12.7 g) and n-butylalcohol (100 mL) were added in a round bottomed flask (250 mL). The mixture was refluxed under an argon atmosphere for 4 h, cooled to room temperature, filtrated and treated under reduced pressure to remove solvent thereof. The residue was purified by column chromatography (dichloromethane: methanol=50: 1) to get 1-[(1-methyl)-4-pyrazolyl]ethanone (2.4 g) as yellowish solid. 1H-NMR (300Hz, CDCl3) delta: 7.88 (s, 1H), 7.85 (s, 1H), 3.93 (s, 3H), 2,42 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29.4% | A solution of 4-iodo-1-methyl-1H-pyrazole (0.80 g, 3.9 mmol) in THF (7.04 g, 8.00 ml, 98 mmol) was cooled at 0 C. A solution of isopropylmagnesium chloride lithium chloride complex in THF (5.42 ml, 4.23 mmol, 0.78 molar) was added dropwise and the reaction was stifled for 1 hour. A solution of <strong>[156353-01-4]N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide</strong> (0.733 g, 4.23 mmol) in THF (2 mL) was added dropwise. Cooling was removed after 15 min and reaction was then stirred for 2 hours. To the mixture was added 2 M HCl (20 mL) and it was extracted with AcOEt (3×25 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography to yield (1-methyl-1H-pyrazol-4-yl)(tetrahydro-2H-pyran-4-yl)methanone (220 mg, 1.13 mmol, 29.4% yield). [0365] 1H NMR (600 MHz, CDCl3) delta 7.87 (s, 1H), 7.87 (s, 1H), 4.03 (ddd, J=11.4, 4.1, 2.4 Hz, 2H), 3.92 (s, 3H), 3.49 (td, J=11.7, 2.3 Hz, 211), 3.06 (tt, J=11.3, 3.8 Hz, 1H), 1.86 (dtd, J=13.8, 11.7, 4.4 Hz, 2H), 1.72 (ddd, J=13.4, 3.7, 2.0 Hz, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 0.116667h;Microwave irradiation; Inert atmosphere; | General procedure: 4-Iodo-1-methyl-1H-pyrazole 1 (101 mg, 0.5 mmol) and phenylboronic 2 (59 mg, 0.5 mmol) were dissolved in DME (3 mL) and H2O (1.2 mL) in a microwave vial under a nitrogen atmosphere. Pd(PPh3)4 (2 mmol%, 11.6 mg) and Cs2CO3 (407.3 mg, 1.25 mmol) were added, and the reaction mixture was irradiated in a microwave apparatus at 90 C for 5-12 min. After the reaction mixture was cooled to ambient temperature, the product was concentrated, and the crude mixture was purified by silica gel column chromatography using petroleum ether/acetone as eluent to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1-(1-Methyl-1H-pyrazol-4-yl)ethan-1-ol. To a resealable vial was added 4-iodo-1-methyl-1H-pyrazole (772 mg, 3.71 mmol), THF (6 mL), and the solution was cooled to 0 C. To this solution was added isopropylmagnesium chloride lithium chloride complex solution (3.42 mL, 4.45 mmol) and the reaction stirred for 30 min (complete disappearance of iodo-pyrazole as detected via LCMS) before cooling to -78 C and addition of N-methoxy-N-methylacetamide (1.18 mL, 11.13 mmol). The solution was stirred at -78 C for 1 h before removing the cold bath and warming to ambient temperature. The solution was diluted with EtOAc and quenched via the addition of 1N HCl. The layers were separated and the aqueous was extracted with EtOAc. The combined organics layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was taken up in MeOH and cooled to 0 C before addition of NaBH4 (281 mg, 7.42 mmol). The reaction was stirred while warming to ambient temperature and quenched when LCMS showed disappearance of starting material. This solution was then diluted with 1N HCl and EtOAc. The layers were separated and the aqueous was extracted with EtOAc (3X). The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified via silica gel chromatography (MeOH:DCM) to afford 1-(1-methyl-1H-pyrazol-4-yl)ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | Under N2, n-BuLi 1 .6M in hexane (6.2 mL; 9.92 mmol) was added at -70C to asolution of 4-iodo-1-methyl-1H-pyrazole (1.7 g; 8.17 mmol) in THF (35 mL). Thereaction mixture was stirred at -70C for 1 hour then, a solution of intermediate 73 (2 g;8.19 mmol) in THF (10 mL) was added drop wise. The reaction mixture was stirred at -70C for 2 hours, allowed to warm up to room temperature and stirred overnight. Thesolution was poured out into a mixture of ice-water and a saturated NH4C1 solution, then EtOAc was added. The organic layer was decanted, dried over MgSO4, filteredand evaporated to dryness. The residue was purified by chromatography over silica gel (irregular SiOH, 50g; mobile phase: gradient from 100% DCM, 0% MeOH to 98%DCM, 2% MeOH, 0.1% NH4OH). The pure fractions were collected and evaporated todryness yielding 320 mg (15%) of intermediate 89. |
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