Structure of 40473-07-2
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CAS No. : | 40473-07-2 |
Formula : | C6H6BrNO |
M.W : | 188.02 |
SMILES Code : | C1=CC=C(N=C1OC)Br |
MDL No. : | MFCD00088345 |
InChI Key : | KMODISUYWZPVGV-UHFFFAOYSA-N |
Pubchem ID : | 256810 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.43 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.34 |
Solubility | 0.0868 mg/ml ; 0.000462 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.15 |
Solubility | 0.133 mg/ml ; 0.000709 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.185 mg/ml ; 0.000986 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 |
-5.3 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) |
1.88 |
* 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 |
---|---|---|
44% | at 20 - 165℃; for 15 h; | [Referential Example 21]; 6-Methoxypyridine-2-carbonitrile; Copper(I) cyanide (2.68 g) was added to 2-bromo-6-methoxypyridine (5.62 g) in N,N-dimethylformamide (112 mL) at room temperature, followed by stirring at 165°C for 15 hours. The resultant mixture was cooled in air. Water and ethyl acetate was added to the mixture. The insoluble matter that was formed in the mixture was filtered by Celite. The filtrate was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate anhydrate, followed by filtration. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane - ethyl acetate), to thereby give the title compound as a solid substance (1.78 g, 44percent) .1H-NMR(400MHz,CDCl3)δ: 3.96(3H,s), 6.95-6.98(1H,m), 7.29-7.31(1H,m), 7.64-7.67(1H,m). MS (EI)m/z: 134 (M+) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | at 20 - 100℃; for 16 h; | Synthesis of 6-methoxypicolinonitrile:To a stirred solution of 2-bromo-6-methoxypyridine (5.0 g, 26.59 mmol) in DMF (50 mL) was added Cu(I)cyanide (7.14 g, 79.77 mmol) at room temperature. The resulting reaction mixture was heated at 100 °C and stirred for 16 h. The reaction mixture was diluted with water, filtered through a pad of celite and the filtrate was extracted with EtOAc. Combined organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified by silica gel column chromatography to afford 6-methoxypicolinonitrile (1.4 g, 39percent) as white solid. 1H-NMR (DMSO d6, 400 MHz): δ 7.94 (t, 1H), 7.64 (d, 1H), 7.18 (d, 1H), 3.92 (s, 3H); LC-MS: 99.14percent; 135.8 (M++l); (column; X-bridge C-18, (50x3.0 mm, 3.5μ); RT 3.31 min. 0.1percent Aq TFA: ACN; 0.8 ml/min); TLC: 10percent EtOAc/Hexane (Rf: |
39% | at 100℃; for 16 h; | Synthesis of 6-methoxypicolinonitrile [0524] To a stirred solution of 2-bromo-6-methoxypyridine (5.0 g, 26.59 mmol) in DMF (50 mL) was added Cu(I)cyanide (7.14 g, 79.77 mmol) at room temperature. The resulting reaction mixture was heated at 100 °C and stirred for 16 h. The reaction mixture was diluted with water, filtered through a pad of celite and the filtrate was extracted with EtOAc. Combined organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified by silica gel column chromatography to afford 6-methoxypicolinonitrile (1.4 g, 39percent) as white solid. 1H-NMR (DMSO d6, 400 MHz): δ 7.94 (t, IH), 7.64 (d, IH), 7.18 (d, IH), 3.92 (s, 3H); LC-MS: 99.14percent; 135.8 (M++l); (column; X-bridge C-18, (50x3.0 mm, 3.5μ); RT 3.31 min. 0.1percent Aq TFA: ACN; 0.8 ml/min); TLC: 10percent EtOAc/Hexane (Rf: 0.3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of the compound of Preparation 113 (5.6 g, 29.8 mmol) in anhydrous tetrahydrofuran (100 ml), at -78° C. and under nitrogen, was added n-butyllithium (1.6M in hexane, 19.5 ml), via syringe. The mixture was stirred at -78° C. for 30 min, before addition of N,N-dimethylformamide (2.5 ml, 32.8 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 18 h, before being acidified with sulphuric acid (2M) and then neutralised by addition of sodium hydrogen carbonate. The mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (4*150 ml). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the title compound (3.0 g). 1H-NMR (CDCl3): 4.01-4.05 (3H), 6.95-7.00 (1H), 7.54-7.58 (1H), 7.70-7.76 (1H), 9.95-9.98 (1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; In acetonitrile; at 80 - 90℃; for 24.0h; | Example 260 2,3-dibromo-6-methoxypyridine NBS (302 g) was added to the compound of Example 259 (295 g) in acetonitrile (575 mL) and the mixture was stirred at 80 to 90 C. for 1 day in a nitrogen atmosphere. After cooling, the crystallized imide was removed by filtration and the filtrate was concentrated. Purification of the resulting residue by silica gel column chromatography (ether:petroleum ether=1:1) gave a 6:1 mixture of the title compound and 2,5-dibromo form. This product was crystallized from cold petroleum ether to afford the title compound as a colorless powder (223 g). 1H NMR (200 MHz, CDCl3) delta 6.68 (1H, d, J=8.7 Hz), 6.60 (1H, d, J=8.7 Hz), 3.91 (3H, s). 13C NMR (50 MHz, CDCl3) delta 162.01, 143.29, 139.68, 113.69, 111.10, 54.40 LRMS (EI+): 264[M+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.9% | Preparation 21 : 2-methoxy-6-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)- nicotinamide; Step 1 : theta-bromo^-methoxy-nicotinic acid; A solution of 2,2,6,6-tetramethylpiperidine (0.766 g, 5.32 mmol) in tetrahydrofuran (5 mL) was cooled to -78C under nitrogen. 2.5M n-butyllithium in hexanes (2.34 ml_, 0.375 g, 5.85 mmol) and the mixture was stirred at -780C for 30 min. To the reaction mixture was added a solution of 2-bromo-6-methoxypridine (1.00 g, 5.32mmol) in tetrahydrofuran (5 mL) dropwise. The reaction was stirred at -78C for 1 h. After this time, an excess of dry ice was added to the reaction mixture and the reaction was allowed to warm to room temperature for 3 h. To the mixture was added water and ethyl acetate, the layers were separated. The aqueous layer was acidified to pH 4. The aqueous layer was extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated to an off-white solid (0.530 g, 42.9 %) 1 H NMR (500 MHz, DMSO-d6) delta ppm 2.52 (2 H, br. s.), 3.32 (1 H, br. s.), 3.92 (1 H, m), 3.90 (1 H, d, J=2.9 Hz), 8.03 (1 H, d, J=7.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; potassium carbonate; N,N-dimethylethylenediamine; In 1,4-dioxane; at 95℃; for 12h;Inert atmosphere; | I1 (1.0 g, 4.5 mmol) was added into 1,4- dioxane (10 mL), and 2-bromo-6-methoxylpyridine (1.02 g, 5.4 mmol, 664 muL), potassium carbonate (622 mg, 4.5 mmol), cuprous iodide (857 mg, 4.5 mmol) and N,N'-dimethylethylenediamine (397 mg, 4.5 mmol, 490 muL) were added while stirring, heated to 95C under nitrogen atmosphere, then reacted for 12 h. 100 mL ammonia was added into the reacted mixture, then extracted by 100 mL EA, the organic phase was washed by 100 mL brine, dried over anhydrous sodium sulfate, filtered and concentrated, the crude product was crystalized by EtOAc, then purified by silica gel chromatography (PE/EA = 10/1 to 2/1), to give the compound 47-1. 1H NMR (400MHz, CDCl3) delta = 8.92 (s, 1H), 7.89 (t, J=8.0 Hz, 1H), 7.43 (d, J=7.2 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 5.83 - 5.69 (m, 1H), 5.07 (d, J=10.4 Hz, 1H), 4.96 (br d, J=17.2 Hz, 1H), 4.84 (d, J=6.0 Hz, 2H), 3.93 (s, 3H), 2.56 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With N-Bromosuccinimide; In acetonitrile; at 20 - 90℃; for 16.0h; | To a stirred solution of 2-bromo-6-methoxypyridine (10 g, 0.053 mol) in dry ACN (100 ml_), was added A/-bromosuccinimide (18.82 g, 0.106 mol) at RT. The reaction mixture was stirred at 90? for 16 h. The completion of reaction was monitored by TLC. After completion, the reaction was filtered through a celite bed, diluted with water (30 mL) and exacted with 10% EtOAc in petroleum ether (2 x 100 mL). The combined organic layer washed with water (10 mL), brine (10mL) dried over Na2SC>4 and concentrated. The resulting crude material was purified by crystallization (5 mL DCM in 50 mL n- pentane). The solid was filtered, washed with n-pentane and then dried unber vacuum to get afford the tittle compound. Yield: 35% (4.92 g, off white solid). 1H NMR (400 MHz, CDCI3): d 7.70 (d, J = 8.4 Hz, 1 H), 6.62 (d, J = 8.4 Hz, 1 H), 3.93 (s, 3H), LCMS: (Method A) 367.9 (M+H), Rt. 2.4 min, 96.7% (Max). |
Tags: 40473-07-2 synthesis path| 40473-07-2 SDS| 40473-07-2 COA| 40473-07-2 purity| 40473-07-2 application| 40473-07-2 NMR| 40473-07-2 COA| 40473-07-2 structure
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H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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