Structure of 39856-56-9
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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. : | 39856-56-9 |
Formula : | C7H9BrN2 |
M.W : | 201.06 |
SMILES Code : | CN(C)C1=CC=C(Br)N=C1 |
MDL No. : | MFCD00100094 |
InChI Key : | BORPINHDNLCKMO-UHFFFAOYSA-N |
Pubchem ID : | 10976514 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
16.13 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.72 |
Solubility | 0.379 mg/ml ; 0.00189 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.97 |
Solubility | 2.18 mg/ml ; 0.0108 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.99 |
Solubility | 0.204 mg/ml ; 0.00102 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 |
-6.11 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) |
2.21 |
* 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 |
---|---|---|
3 g (80%) | With potassium carbonate;Pd(PPh3)4; In 1,2-dimethoxyethane; dichloromethane; water; | (2) Synthesis of 2-(2,4-difluorophenyl)-5-dimethylamino-pyridine <strong>[39856-56-9]2-bromo-5-dimethylaminopyridine</strong> (3.2 g, 16 mmol), 2,4-difluorophenylboronic acid (4.8 g, 30 mmol), K2CO3 (13 g, 94 mmol) and Pd(PPh3)4 (400 mg, 0.35 mmol) in a degassed mixture of DME/H2O (60/50 ml) were refluxed 24 hours under nitrogen. After being cooled to room temperature, the organic layer was separated and the aqueous phase extracted with EtOAc (100 ml). The combined organic fractions were washed with brine, dried over MgSO4 and evaporated to dryness. The crude compound was purified by column chromatography (SiO2, CH2Cl2 then CH2Cl2/MeOH: 97/3). The resulting brown solid was dissolved in CH2Cl2 and decolorized with charcoal. Filtration and evaporation of the solvent afford 3 g (80%) of the desired compound as a slightly yellow crystalline solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 3.03 (s, 6H), 6.9-7.1 (m, 3H), 7.60 (dd, J=2.5*9 Hz, 1H), 7.95 (m, 1H), 8.24 (d, J=2.5 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.2 g (40%) | With formaldehyd; aqueous KOH; HCO2H; In dichloromethane; water; Petroleum ether; | (1) Synthesis of 2-bromo-5-dimethylaminopyridine 2-bromo-5-aminopyridine (11.7 g, 67.6 mmol) was added portionwise to HCO2H (20 ml) at 0 C. Formaldehyde (37% in water, 17 ml, 210 mmol) was then added and the mixture heated to reflux for hours. The reaction was then cooled to room temperature and an aqueous KOH solution (1N, ml) was added. The mixture was extracted with Et2O (3*100 ml) and the combined extract was dried over MgSO4, filtered and evaporated to dryness. The residual oil was purified by flash chromatography on silica (CH2Cl2). The yellowish solid was dissolved in the minimum volume of CH2Cl2, petroleum ether (150 ml) was added and the solution was stand in the fridge overnight. The white crystalline solid was filtered and washed with small portion of cold petroleum ether to afford 5.2 g (40%) of the desired compound as white crystalline solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 2.96 (s, 6H), 6.87 (dd, J=2.5*9 Hz, 1H), 7.25 (d, J=9 Hz, 1H), 7.84 (d, J=2.5 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
600 mg (46%) | With n-butyllithium; sulfuric acid; In tetrahydrofuran; methanol; dichloromethane; water; Petroleum ether; | (1) Synthesis of 5-dimethylamino-2-carboxymethyl-pyridine To a solution of <strong>[39856-56-9]2-bromo-5-dimethylaminopyridine</strong> (1.45 g, 7.2 mmol) in THF (100 ml) cooled to -78 C. was dropwise added nBuLi (1.6M, 6.3 ml, 10 mmol). The resulting orange solution was stirred at -78 C. for 40 minutes under nitrogen. CO2 (from dry-ice) was then bubbled into the solution during 3 hours while the temperature was allowed to reach room temperature. MeOH (2 ml) was then added and the solvent removed under vacuum. MeOH (100 ml) and concentrated H2SO4 (4 ml) were added and the resulting mixture refluxed overnight. The solvent was removed under vacuum and water (100 ml) was added. The mixture was neutralized with aqueous K2CO3 and extracted with CH2Cl2 (3*50 ml). The combined organic fractions were washed with brine, dried over MgSO4 and evaporated. The residue was purified by column chromatography (SiO2, CH2Cl2/MeOH: 95/5). The obtained orange oil was dissolved in CH2Cl2 (1 ml) and petroleum ether (100 ml) was added. The solution was stand in the fridge overnight. The formed precipitate was filtered and washed with small portions of cold petroleum ether to afford 600 mg (46%) of the desired compound as a slightly yellow solid. 1H-NMR (CDCl3, 298K, 200 MHz, delta ppm) delta 3.09 (s, 6H), 3.96 (s, 3H), 6.94 (dd, J=2.5*9 Hz, 1H), 7.99 (d, J=9 Hz, 1H), 8.17 (d, J=2.5 Hz, 1H). 13C-NMR (CDCl3, 298K, 50 MHz, delta ppm) delta 39.7, 52.2, 116.8, 126.2, 133.9, 134.9, 147.7, 166.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 130℃; for 16h;Inert atmosphere; | To a stirred solution of lH-pyrrolo[2,3-c]pyridine (100 mg, 0.84 mmol) in dimethyl sulfoxide (30 mL) were added <strong>[39856-56-9]6-bromo-N,N-dimethylpyridin-3-amine</strong> (204 mg, 1.01 mmol), dimethylglycine (52 mg, 0.51 mmol), copper(I) iodide (97 mg, 0.51 mmol) and cesium carbonate (1.1 g, 3.39 mmol) at ambient temperature. The resulting mixture was stirred for 16 hours at 130 C under nitrogen atmosphere. After cooling down to ambient temperature, the reaction mixture was quenched with water (80 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers was washed with brine (4 x 80 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 1-5% methanol in dichlorom ethane to afford N,N- dimethyl-6-(lH-pyrrolo[2,3-c]pyridin-l-yl)pyridin-3-amine as a light yellow solid: MS (ESI, m/z): 239.0 [M + 1]+; 1H MR (300 MHz, OMSO-d6) delta 9.47 (s, 1H), 8.22 (d, J= 5.1 Hz, 1H), 8.11-8.09 (m, 2H), 7.66 (s, 1H), 7.62-7.61 (m, 1H), 7.40-7.35 (m, 1H), 6.75 (d, J= 3.3 Hz, 1H), 3.02 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | To a solution of 6- bromopyridin-3 -amine (300 mg, 1.73 mmol) in tetrahydrofuran (30 ml) was added 1 M solution of lithium bis(trimethylsilyl)amide (3.46 mL, 3.46 mmol) in tetrahydrofuran over 5 min at - 78 C under nitrogen atmosphere. After stirring for 30 min at -78 C, iodomethane (566 mg, 3.99 mmol) was added. The resulting mixture was stirred for 1 hour at ambient temperature and then quenched by the addition of saturated aqueous solution of ammonium chloride (50 mL). The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers was washed with brine (2 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 1-10% ethyl acetate in petroleum ether to afford 6-bromo- N,N-dimethylpyridin-3 -amine as a light yellow solid: MS (ESI, m/z): 201.0, 203.0 [M + 1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.43 g | With formic acid; at 90℃; for 16h; | Step a. To a solution of 6-bromopyridin-3 -amine (CAS Number 97-65-4) (1 g, 5.78 mmol) in formic acid (5 ml) was added para-formaldehyde (1.5 g, 1.5 eq w/w) at rt. The reaction mixture was heated at 90C for 16 hr. The resulting reaction mixture was poured into ice cold water, basified using solid sodium carbonate and extracted using EtOAc (30ml x 3). The organic layer was combined and dried over Na2S04 concentrated under reduced pressure. The obtained residue was purified using column chromatography (20% EtOAc in hexane) yielding 6-bromo-N, N-dimethylpyridin-3 -amine (0.43 g, 2.160 mmol). LCMS: Method C, 1.77 min, MS: ES+ 201.14. NMR (400 MHz, DMSO-d6) delta ppm 8.31-8.32 (d, 1 H), 7.84-7.85 (d, 1 H), 7.33-7.35 (d, 1 H), 2.91 (s, 6 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.45 g | With iodine; silver sulfate; In ethanol; at 20℃; for 2h; | Step b. To a solution of <strong>[39856-56-9]6-bromo-N,N-dimethylpyridin-3-amine</strong> (1.2 g, 6.03 mmol) in ethanol (20 ml) were added silver sulphate (2.067 g, 6.63 mmol) and iodine (1.81 g, 7.24 mmol) at rt. The resulting reaction mixture was stirred at rt for 2 hr. The resulting reaction mixture was poured into water (50 ml), basified using solid sodium bicarbonate and extracted using EtOAc (50ml x 2). The organic layer was combined and washed with solution of sodium thiosulphate (50 ml), dried over Na2S04 and concentrated under reduced pressure. The obtained residue was purified using column chromatography (30% EtOAC in hexane) yielding 6-bromo-2-iodo-N,N-dimethylpyridin-3 -amine (1.45 g, 4.45 mmol). LCMS: Method C, 2.17 min, MS: ES+ 327.13. |
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