Structure of 83004-13-1
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 83004-13-1 |
Formula : | C7H8BrN |
M.W : | 186.05 |
SMILES Code : | CCC1=CC=CC(Br)=N1 |
MDL No. : | MFCD11869660 |
InChI Key : | TYOSQEKDQKYBLX-UHFFFAOYSA-N |
Pubchem ID : | 12954800 |
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 | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.81 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.4 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.13 |
Solubility | 0.139 mg/ml ; 0.000744 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.63 |
Solubility | 0.432 mg/ml ; 0.00232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.67 |
Solubility | 0.0398 mg/ml ; 0.000214 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 |
-5.51 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 |
0.55 |
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) |
1.75 |
* 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 |
---|---|---|
75% | Preparation 23 Synthesis of 2-bromo-6-ethyl-pyridine Add under nitrogen a solution of 2.5 M n-butyllithium in hexanes (186.74 mL, 0.467 mol) over 41 min to a solution of diisopropylamine (68.7 mL, 0.488 mol) in tetrahydrofuran (745 mL, 9.16 mol) at -78° C. (dry-ice/acetone bath). Stir for 15 min and add 2-bromo-6-methylpyridine (49.3 mL, 0.424 mol) dropwise over 22 min. Stir 15 min, add methyl iodide (52.87 mL, 0.848 mol) dropwise over 1 hour and then warm to room temperature over 1.5 hour. Add water (250 mL) while cooling with a dry-ice/acetone bath and separate the layers. Extract the aqueous phase twice with ethyl acetate (300 mL). Combine the organic phases, concentrate and purify by silica gel chromatography, gradient eluding from 100:0 to 80:20 using hexanes:ethyl acetate, to give the title compound as a yellow oil (59.74 g, 75percent). 1H NMR (CDCl3) delta 1.28 (t, 3H), 2.80 (q, 2H), 7.11 (d, 1H), 7.27 (d, 1H), 7.45 (t, 1H). | |
46% | To a solution of 2-bromo-6-methylpyridine (CAS 5315-25-3) (2.0 g, 11.7 mmol, 1.0 eq) in THF (10 mL) was added LDA (12.3 mL, 12.3 mmol, 1.05 eq) at -78 °C. After stirring at -78 °C for 1 h, CH3I (1.8 g, 12.3 mmol, 1.05 eq) was added to the mixture. The mixture was stirred at rt for 3 h. The mixture was quenched with sat. NH4C1 (2 mL), diluted with water (50 mL) and extracted with EA (2 x 100 mL). The combined organic phase was washed with brine and dried over Na2S04. After concentration, the residue was purified by silica gel chromatography with PE/EA (20/1) as eluent to give 2-bromo-6-ethylpyridine. 1.0 g, as a yellow solid, Y: 46percent. ESI-MS (M+H)+: 185.9, 187.9. | |
46% | To a solution of 2-bromo-6-methylpyridine (CAS 53 15-25-3) (2.0 g, 11.7 mmol, 1.0 eq) in THF (10 mL) was added LDA (12.3 mL, 12.3 mmol, 1.05 eq) at -78 °C. After stirring at -78°C for 1 h, CH3I (1.8 g, 12.3 mmol, 1.05 eq) was added to the mixture. The mixture was stirred atrt for 3 h. The mixture was quenched with sat. NH4C1 (2 mL), diluted with water (50 mL) and extracted with EA (2 x 100 mL). The combined organic phase was washed with brine and dried over Na2504. After concentration, the residue was purified by silica gel chromatography with PE/EA (20/1) as eluent to give 2-bromo-6-ethylpyridine. 1.0 g, as a yellow solid, Y: 46percent. ESIMS (M+H): 185.9, 187.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.0 g (>100%) | With peracetic acid; In acetic acid; | b 2-Bromo-6-ethyl-pyridine 1-oxide To a solution of <strong>[83004-13-1]2-bromo-6-ethyl-pyridine</strong> (15.4 g, 82.8 mmol) (S. G. Davies and M. R. Shipton, J. Chem. Soc., Perkin Trans. 1, 1991, 3, 501) in acetic acid (15 ml) was added peracetic acid (26 ml of a 39percent solution) maintaining T<50° C. After complete addition the mixture was stirred at 50° C. for 5 hr and then cooled to room temperature (rt). Crushed ice (40 g) was added and the pH was adjusted to pH 12 with 40percent aqueous KOH solution. After extraction with CHCl3 (6*60 ml) the combined organic phases were dried (Na2CO3) and evaporated to give 20.0 g (>100percent) of the title compound, MS: m/e=201 (M+) as a yellow oil. |
20.0 g (>100%) | With peracetic acid; potassium hydroxide; In acetic acid; | a 2-Bromo-6-ethyl-pyridine 1-oxide To a solution of <strong>[83004-13-1]2-bromo-6-ethyl-pyridine</strong> (15.4 g, 82.8 mmol) (S. G. Davies and M. R. Shipton, J. Chem. Soc., Perkin Trans. 1, 1991, 3, 501) in acetic acid (15 ml) peracetic acid (26 ml of a 39percent) solution) was added maintaining T<50° C. After completed addition the mixture was stirred at 50° C. for 5 hr and then cooled to rt. Crushed ice (40 g) was added and the mixture was made basic (pH 12) using 40percent KOH solution. After extraction with CHCl3 (6*60 ml) the combined organic phases were dried (Na2CO3) and evaporated to give 20.0 g (>100percent) of the title compound, MS: m/e=201 (M+) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 2-bromo-6-methylpyridine (302 mg, 1.76 mmol) an 10 mL THF at -78° C., was added a solution of lithium diisopropylamide (1.8 M in heptane/THF/ethylbenzene, 1.07 mL, 1.93 mmol). The bright orange/red mixture was treated with iodomethane (0.20 mL, 3.2 mmol). The mixture was stirred at -78° C. for 10 min, then was removed from the ice bath and stirred 30 min. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with water (2.x.) and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (0 to 20percent EtOAc/hexanes gradient) to afford 157 mg of Intermediate 163.1 as a colorless oil. LCMS (2 min gradient) RT=1.26 min, 186.0 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Preparation 33 Synthesis of 2-ethyl-6-tributylstannanyl-pyridine Add under nitrogen a solution of tert-butyllithium in pentane (1.5 M, 80.3 mL, 120.5 mmol) dropwise over 1 hour to a cooled solution of <strong>[83004-13-1]2-bromo-6-ethyl-pyridine</strong> (10.19 g, 54.77 mmol) in anhydrous diethyl ether (101.9 mL) at -78° C. at a rate so that the internal reaction temperature does not exceed -75° C. Stir 15 min and add tri-n-butyltin chloride (16.25 mL, 57.51 mmol) dropwise at a rate so that the internal reaction temperature does not exceed -70° C. Warm to room temperature, add water and separate the layers. Extract the aqueous phase once with diethyl ether. Dry the combined organic layers over sodium sulfate, filter and concentrate to give the title compound as a pale yellow liquid (24.05 g, 94percent) that is subsequently used without further purification. 1H NMR (CDCl3) delta 0.88 (t, 9H), 1.09 (m, 6H), 1.32 (m, 9H), 1.56 (m, 6H), 1.57 (m, 6H), 2.80 (q, 2H), 6.95 (m, 1H), 7.17 (d, 1H), 7.38 (t, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Step 2:To a solution of LDA (6.6 mmol) in THF (10 mL) at -78° C. was added compound 11-1 (1.12 g, 6 mmol) in THF (4 mL+1 mL rinse). The resulting deep orange solution was stirred at -78° C. for 5 min. Then a solution of iodide 9-1 (2.35 g, 7.2 mmol) in THF (6 mL+2 mL rinse) was added. The reaction mixture was warmed to room temperature overnight, poured into brine and extracted with EtOAc (3.x.). The combined organic layer was dried (Na2SO4), filtered and concentrated. Purification of the residue with flash column chromatography with EtOAc in hexane (1percent to 8percent gradient over 20 min) followed by distillation gave 0.37 g of the desired product 11-2 as an orange oil (37percent yield).1HNMR (CDCl3, 300 Hz): 7.43 (t, J=7.7 Hz, 1H), 7.27 (dd, J=0.9, 7.8 Hz, 1H), 7.06 (dd, J=0.9, 7.5 Hz, 1H), 2.89-2.77 (m, 1H), 1.75-1.64 (m, 1H), 1.62-1.48 (m, 1H), 1.45-1.38 (m 12H), 1.30-1.13 (m, 7H), 1.08 (s, 6H); 13CNMR (CDCl3, 75 Hz): 177.4, 168.6, 141.6, 138.5, 125.3, 120.1, 79.6, 42.6, 41.8, 40.6, 36.8, 28.1, 28.0, 25.2, 25.0, 20.6; MS calcd for C19H31BrNO2 [M+H]+: 386. Found: 386. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | 2-Bromo-6-ethylpyridine (18.2 mmol) was dissolved in 40 ml of tetrahydrofuran [THF], and 1.65 M hexane solution of n-butyllithium (19.1 mmol) was added dropwise thereto with cooling with dry ice-ethanol bath and with stirring.Then, the mixed liquid obtained was stirred for 10 minutes to obtain a reaction mixture.To the reaction mixture obtained, chlorobis (3,5-dimethylphenyl) phosphide (16.8 mmol) dissolved in 20 ml of THF was added, and the temperature was brought back to room temperature and the stirring was carried out under room temperature for 3 hours to conduct the reaction.To the solution obtained, a little amount of water was added to quench the reaction, and a saturated aqueous sodium chloride solution was further added thereto.Next, to the solution obtained, ethyl acetate was added to stir and separate, and then, an ethyl acetate phase (an organic phase) was collected by separation.This organic layer was dried over anhydrous magnesium sulfate, and filtrated, and the filtrate obtained was concentrated under reduced pressure.The concentrate obtained was purified twice with silica gel chromatography (developer: hexane/ethyl acetate = 20/1) to obtain 2.07 g of bis(3,5-dimethylphenyl)(6-ethyl-2-pyridyl)phosphine (Yield 33percent).The purity calculated with 1H-NMR analysis was 97percent.1H-NMR (CDCl3, 600 MHz) : 5 7.44 (td, 1H, J=8.2 Hz), 7.03-6.95 (m, 7H), 7.03 (d, 1H, J=8 Hz), 6.83 (d, 1H, J=8 Hz), 2.83 (q, 2H, J=8 Hz), 2.26 (s, 12H), 1.27 (t, 3H, J= 8Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19%; 26% | The preparation of 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole was the same as that of 6-bromo-l-(6-methylpyridin-2-yl)-lH-indazole. The mixture of 6-bromo-l-(6- ethylpyridin-2-yl)-lH-indazole and 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole was purified by pre-TLC (PE/EA = 10/1) to give 41-02-0002 and 6-bromo-2-(6-ethylpyridin-2- yl)-2H-indazole. Rf value of 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole is more than that of 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole. 6-bromo-l-(6-ethylpyridin-2-yl)-lH-indazole, 230 mg, as a yellow solid, Y: 26percent. ESI-MS (M+H)+: 302.0, 304.0. 6-bromo-2-(6-ethylpyridin-2-yl)-2H-indazole, 170 mg, as a yellow solid, Y: 19percent. ESI-MS (M+H)+: 302.0, 304.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | A solution of 3.0 g (16.1 mmol) of <strong>[83004-13-1]2-bromo-6-ethylpyridine</strong> in25 mL of tetrahydrofuran was added dropwise at 78 C to 6.5 mL (16.1 mmol) of n-BuLi (2.5 M in n-hexane). The resultingreaction mixture was stirred for 45 min at this temperature. Thereafter,2.1 g (16.1 mmol) of 1-indanone dissolved in 25 mL oftetrahydrofuran was added to the stirred solution. After a reactiontime of 2 h between 60 and 78 C, the solution was left at roomtemperature overnight. The reaction was then hydrolyzed with50 mL of saturated ammonium chloride solution. After extractionwith EtOAc (50 mL 3), the combined organic phase was concentrated,and the residue was treated at 0 C with 100 mL of sulfuricacid drop-wisely (85%). The dark red solution was stirred for 2 h atthis temperature and then poured into 150 g of ice water. Theresulting reaction mixture was neutralized with solid sodiumhydroxide and then washed with diethyl ether. Elution withEtOAc/petroleum ether to give 1.60 g (45%) of 3-(6-ethyl-2-pyridyl)indene as a colorless oil. HR-MS (ESI): Calcd for C16H15N +H,222.1283. Found, 222.1282. 1H NMR (400 MHz, CDCl3, ppm): d[8.19 (d, J = 7.6 Hz, 1H), 7.69 (t, J = 8.4 Hz, 1H), 7.54 (t, J = 6.8 Hz,2H), 7.38 (t, J = 7.2 Hz, 1H), 7.29 (t, J = 7.2 Hz, 1H), 7.15 (d,J = 7.6 Hz, 1H), 7.00 (s, 1H) (Py-H, ArH and Cp-H)], 3.57 (s, 2H,Cp-H), 2.96 (q, J = 7.6 Hz, 2H, CH2), 1.43 (t, J = 7.6 Hz, 3H, CH3).13C NMR (100 MHz, CDCl3, ppm): 163.1, 154.4, 144.7, 143.2,136.7, 133.4, 126.2, 124.9, 123.8, 122.3, 120.4, 119.2, 38.3, 31.5,14.0. |