Structure of 856013-04-2
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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. : | 856013-04-2 |
Formula : | C5H5BrN2O2S |
M.W : | 237.07 |
SMILES Code : | O=S(C1=NC(Br)=CC=C1)(N)=O |
MDL No. : | MFCD14702808 |
InChI Key : | WAYSQXHNUWIYPM-UHFFFAOYSA-N |
Pubchem ID : | 57345816 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
81.43 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.77 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.13 |
Solubility | 1.75 mg/ml ; 0.00737 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.06 |
Solubility | 2.06 mg/ml ; 0.0087 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.45 |
Solubility | 0.841 mg/ml ; 0.00355 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 |
-7.2 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.1 |
* 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 |
---|---|---|
ii) 6-Bromopyridine-2-sulfonamide 6-Bromopyridine-2 (1H)-thione (114 mg) was added to a mixture of bromine (0.061 ml) in water (3.6 ml) and ice (1.8g) and the mixture was stirred at 0C for 2 h. Aqueous ammonia (2 ml) was added and the mixture was stirred for 1 h at 20 C and then heated to reflux. The reaction mixture was filtered while hot and then allowed to crystallise. The solid was collected by filtration and then purified by chromatography on a 10 g silica SPE cartridge eluting with ethyl acetate-cyclohexane (3: 2) to give the title comound (63mg) LCMS RT=1. 6 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; tetrabutylammomium bromide; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | c) 6-(8-Oxo-5,6,7,8-tetrahydro-naphthalen-2-yl)-pyridine-2-sulfonamide6-Bromo-pyridine-2-sulfonamide (65mg, 0.27 mmol), 7-(4,4,5,5-Tetramethyl- [l,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-naphthalen-l-one (97mg, 0.36 mmol), tetrabutylammonium bromide (TBAB) (lOmg, 0.04 mmol) and Pd(PPh3)2Cl2 (13mg, 0.02 mmol) in dioxane:water (1.2 mL/0.6 mL) were heated at 1000C in a microwave reactor for 1 hour. After this time, water was added and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with water and brine and dried over Na2SO4. Concentration afforded a brown solid which was triturated with Et2O. An off-white solid was obtained. Analysis (NMR) showed presence of impurities but the compound was on-reacted without further purification. NMR 1H (d6-DMSO, ppm): 8.6 (d, J = 2.1 Hz, IH), 8.36 (dd, J = 8.1 and 2.1 Hz, IH), 8.20 (dd, J = 9.03 and 1 Hz, IH), 8.11 (t, J = 7.6 Hz, IH), 7.85 (dd, J = 7.6 and 1 Hz, IH), 7.53-7.50 (m, 3H), 3.01-2.98 (m, 2H), 2.66-2.62 (m, 2H), 2.10-2.04 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With trifluoroacetic acid; at 60℃; for 3h; | b) 6-Bromo-pyridine-2-sulfonamideTFA (2 mL) was added to 6-bromo-pyridine-2-(N-fert-butyl)-sulfonamide (478mg, 1.63 mmol) and the reaction was stirred at 6O0C for 3 hours. TFA was removed under vacuum and a mixture of Petroleum ether and Et2O was added leading to the precipitation of a brown solid. It was collected and triturated three times with Et2O. A white solid was obtained (125mg, 32%). NMR 1H (de-DMSO, ppm): 7.98 (t, J = 7.5 Hz, IH), 7.91 (dd, J = 7.5 and 1.2 Hz, IH), 7.87 (dd, J = 7.5 and 0.9 Hz, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate; In acetonitrile; at 20℃; for 16h;Cooling; | <strong>[856013-04-2]6-Bromopyridine-2-sulphonamide</strong> (0.5 g, 2.11 mmol, prepared by the methods described in WO2005/058299) and potassium carbonate (2.92 g, 21.1 mmol) were initially charged in acetonitrile (10 ml). While cooling with ice, acetyl chloride (1.16 g, 14.8 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure, and the residue was taken up in water and acidified with dilute hydrochloric acid solution. It was extracted with ethyl acetate and the solvent was removed under reduced pressure. This gave 0.54 g (85% of theory) of N-[(6-bromopyridin-2-yl)sulphonyl]-acetamide.HPLC-MS: LogP(HCOOH): 0.95; mass (m/z): 278.9 (M+H)+;1H NMR (d6-DMSO): 1.99 (s, 3H), 7.99-8.01 (m, 1H), 8.08 (t, 1H), 8.11-8.13 (m, 1H), 12.48 (s, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; at 70℃; for 18h;Inert atmosphere; | Under argon, 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]pyridine (0.2 g, 0.74 mmol, prepared by the methods described in WO 2011/045224), 6-bromopyridin-2-sulphonamide (0.175 g, 0.74 mmol) and tetrakis(triphenylphosphine)palladium (0.025 g, 0.022 mmol) were added to a mixture, degassed by means of argon, of sodium carbonate solution in water (2.9 ml, 2 M/L) and acetonitrile (4 ml). The reaction mixture was stirred at 70 C. for 18 h. After cooling, the reaction mixture was poured onto water and the precipitated crystals were filtered off with suction. They were subsequently stirred with diethyl ether and filtered off with suction. This gave 0.23 g (97% of theory) of 6-[1-(pyridin-3-yl)-1H-pyrazol-4-yl]pyridine-2-sulphonamide.HPLC-MS: LogP(HCOOH): 0.99; mass (m/z): 302.1 (M+H)+ 1H NMR (d6-DMSO): 7.43 (s, 2H), 7.60-7.63 (m, 1H), 7.76 (d, 1H), 8.00 (d, 1H), 8.11 (t, 1H), 8.28-8.31 (m, 1H), 8.53 (s, 1H), 8.58-8.60 (m, 1H), 9.16-9.17 (m, 1H), 9.33 (s, 1H) ppm |
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