Structure of 7745-93-9
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CAS No. : | 7745-93-9 |
Formula : | C7H6BrNO2 |
M.W : | 216.03 |
SMILES Code : | O=[N+](C1=CC=C(C)C(Br)=C1)[O-] |
MDL No. : | MFCD00007195 |
Boiling Point : | No data available |
InChI Key : | XFZFJQHXWJIBQV-UHFFFAOYSA-N |
Pubchem ID : | 82189 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.24 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.77 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.27 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.56 |
Solubility | 0.0597 mg/ml ; 0.000277 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.88 |
Solubility | 0.0288 mg/ml ; 0.000133 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.02 |
Solubility | 0.204 mg/ml ; 0.000946 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 |
-5.32 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 |
2.0 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) |
1.9 |
* 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 |
---|---|---|
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In diethylene glycol dimethyl ether; water; at 90℃; for 16.5h; | Step 1.Synthesis of 3-chloro-4-(2-methyl-5-nitrophenyl)pyridine nitrogen was bubbled through a solution of 2-bromo-1-methyl-4-nitrobenzene (1 eq) in dimethoxyethane and water (3:1) for 0.5 h. bis(diphenylphosphino)ferrocene Palladium(II)chloride (0.05 eq) followed by 3-chloro-4-pyridine boronic acid hydrate (1 eq) and sodium carbonate (3 eq) was added and the mixture was heated to 90 C. for 16 h under nitrogen.The reaction mixture was concentrated and partitioned between ethyl acetate and water.The organic layer was washed with brine and dried with sodium sulfate and concentrated.Purification on silica gel gave 3-chloro-4-(2-methyl-5-nitrophenyl)pyridine. MS: MH+=248. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; for 24.0h; | A mixture of compound 1 (250.0 g, 1.16 mol), Zn(CN)2 (135.0 g, 1.16 mol) and Pd(PPh3)4 (25 g, 0.02 mol) in dry DMF (1500 mL) was stirred at 80 C for 24 hours under N2. TLC (petroleum ether: ethyl acetate = 10:1) showed the reaction was complete, then the mixture was poured into toluene (1500 mL) and washed with 2 N NH3 H2O (800 mLx2). The aqueous layer was extracted with toluene (800 mLx2). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude product, which was purified by column chromatography (first petroleum ether, then petroleum ether: ethyl acetate 10:1) to afford compound 2 (25.5 g, yield: 42%) as a grey solid and recover compound 1 (170 g) as yellow solid.1H NMR (300 MHz, CDCI3): delta 8.46-8.47 (d, J = 3.0 Hz, 1 H), 8.31-8.34 (dd, J = 9.0 Hz, 1 H), 7.53-7.56 (d, J = 9.0 Hz, 1 H), 2.68 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With copper(l) iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 120℃; for 0.5h;Microwave irradiation; | The mixture of 4-(Pyridin-3-yl) pyrimidin-2- amine (0.378 g,2.2 mmol), copper iodide (0.5 mmol) and anhydrous K2CO3(4 mmol), Dioxane (5 mL), 2-bromo-1-methyl-4- nitrobenzene(2 mmol), and DMEDA (0.5 mmol) was irradiated in the microwave synthesizer and heated at 120 C for 30 min. After completion of the reaction, ammonium hydroxide and brine solution was added andthen extracted with ethyl acetate. The organic layer was dried overanhydrous sodium sulphate, the solvent was evaporated in buchirotary evaporator and the resulting solid was dried under vacuum.The crude was purified by using silica gel column chromatographyusing ethyl acetate: chloroform (50:50) to yield 0.498 g (79.0percent) ofthe imatinib intermediate compound as yellowish powder. Melting point194-196 °C. ES-MS (M1) found (m/z): 308.1. 1H NMR (DMSOd6):2.49(S, 3H); 7.32-7.37 (m, 1H); 7.40-7.48 (m, 1H); 7.49e7.51(m, 1H); 7.85-7.88 (m, 1H); 8.02 (m, 1H); 8.48-8.51 (m, 1H);8.57-8.59 (m, 1H); 9.20(S, 1H); 9.29 (S, 1H). |
60% | With copper(l) iodide; potassium carbonate; potassium iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 110℃; for 24h;Inert atmosphere; Schlenk technique; | 4-(Pyridine-3-yl) pyridine-2-amine (8.60 g, 0.05 mol), CuI (2.39 g, 0.0125 mmol), anhydrous K2CO3 (14.0 g, 0.1 mol), KI (2.08 g, 0.0125 mol) were added to a Schlenk-type three-neck flask fitted with a thermometer, magnetic stirbar, and septum. The flask was evacuated and back filled with N2 three times. Dioxane (250 mL) and 2-bromo-4-nitrotoluene (9.82 g, 0.045 mol) were added to the flask. Finally, N,N'-dimethylethylenediamine (1.10 g, 0.0125 mol) was added by syringe at room temperature with stirring. The reaction mixture was stirred at 110° C. under N2 for 24 hours and then cooled to room temperature. Ammonia (30percent, 100 mL) and saturated NaCl (400 mL), were added to the reaction mixture which was then extracted with ethyl acetate (500 mL*3). The organic phase was dried over Na2SO4 and a yellow solid was obtained after the solvent was removed under reduced pressure. The crude product was purified by column chromatography (biotage: DMC/Methanol, 1-8percent, 20 CV). The desired product was obtained as a yellow solid (8.3 g, yield: 60percent); 1H NMR (500 MHz, CDCl3) delta 2.49 (s, 3H), 7.36 (m, 1H), 7.15 (br., 1H), 7.35 (d, 1H), 7.38 (d, 1H), 7.52 (m, 1H), 7.88 (d, 1H), 8.55 (d, 1H), 8.60 (d, 1H), 8.76 (d, 1H), 9.28 (s, 1H), 9.50 (s, 1H). LC-MS (m/z) calculated, 307.3, found, 308.3 [M+H]+. |
With potassium tert-butylate; In dimethyl sulfoxide; at 120℃; for 12h; | 2-bromo-1-methyl-4-nitrobenzene(0.63 g, 2.9 mmol), <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> (1) (0.60 g, 3.5 mmol), and KOtBu(0.49 g, 4.40 mmol) was added flask containing PS-CuO (57.5 mg, 20 wtpercent of CuOin PS, 0.145 mmol based on Cu) in 15 mL DMSO. The resulting mixture was heatedto 120oC and stirred for 12 h. Aftercooling, the mixture was poured into EtOAc (20.0 mL) and washed with water (2 × 10.0 mL).The organic layer was separated and dried over MgSO4, and thenevaporated under reduced pressure. The resulting mixture was reacted with stannouschloride (1.64 g, 8.70 mmol) and 1.64 mL of Con. HCl in MeOH (10 mL) at at 50 oCfor 8 h. After completion the reaction mixture was poured into crushed ice followedby basification with sodium bicarbonate. The layer was separated and dried overanhydrous MgSO4, evaporated under reduced pressure to afford the crudeproduct which was purified by using column chromatography(hexane : EtOAc = 4:1) obtainedas yellow solid 67percent (0.54 g, 1.95 mmol).1HNMR (300 MHz, CDCl3) delta 9.25 (dd, J= 1.5 Hz, 1H), 8.71 (dd, J1= 3.3 Hz, J2 = 1.5 Hz,1H), 8.48 (d, J = 5.1 Hz, 1H), 8.35-8.31(m, 1H), 7.59 (d, J = 2.1 Hz, 1H), 7.43 ? 7.38 (m, 1H), 7.12 (d, J = 5.4Hz,1H) 7.03(bs, 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.41 (dd, , J1 = 5.7 Hz, J2= 2.4 Hz, 1H), 3.59(bs, 2H), 2.24(s, 3H). 13C NMR (75 MHz, CDCl3): delta 162.5, 160.7, 159.0, 151.4, 148.5, 145.1,137.9, 134.4, 132.7, 131.0, 123.5, 118.1, 110.6, 108.4, 108.0 HRMS(ESI) calcd. for C16H16N5 [M+H]+ 278.1406, found 278.1400. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In a dried schlenk flask (25mL in volume) equipped with a stirring bar were placed with 2-bromo-4-nitrotoluene (54.0mg, 0.25mmol, 1.0 eq.), and <strong>[66521-66-2]4-(3-pyridinyl)-2-pyrimidine amine</strong> (43.0 mg, 0.25mmol, 1.0 eq.), Pd2(dba)3 (11.5mg, 0.0125mmol, 5molpercent), BINAP (18.7mg, 0.03mmol, 12molpercent), Cs2CO3 (163.0mg, 0.5mmol, 2.0 eq.). After evacuation and refill with dry nitrogen for three times, dioxane (3.0mL) was added with syringes under a stream of nitrogen. The resulting mixture was allowed to stir at 100°C for 24h, and dioxane was removed. Then, B2pin2 (1.0mmol, 4.0 eq.) and KOt-Bu (0.5mmol, 2.0 eq.) in 1.0mL iPrOH was added and the mixture was then stirred in the preheated oil bath at 110°C for 4h. Purification by flash chromatography on silica gel using dichloromethane: methanol=50: 1.8 was obtained as yellow solid (57.5mg, isolated yield 83percent). When expanded to 1.0mmol, 0.208g product can be obtained, yield 75percent. Melting point (°C): 133.0?135.0; 1H NMR (400MHz, DMSO?d6) delta 9.27 (dd, J=2.0, 0.4Hz, 1H), 8.73?8.68 (m, 2H), 8.48 (d, J=4.8Hz, 1H), 8.44?8.39 (m, 1H), 7.54 (ddd, J=0.8, 4.8, 5.6Hz, 1H), 7.37 (d, J=4.8Hz, 1H), 6.89 (d, J=8.0Hz, 1H), 6.82 (d, J=2.4Hz, 1H), 6.36 (dd, J=8.0, 2.4Hz, 1H), 4.87 (s, 2H), 2.08 (s, 3H); 13C NMR (101MHz, DMSO?d6) delta 161.96, 161.78, 159.82, 151.79, 148.60, 147.24, 138.42, 134.73, 132.77, 130.80, 124.28, 119.78, 111.58, 111.39, 107.54, 17.70; HRMS (ESI) m/z calcd for C16H16N5+ (M+H)+ 278.14002, found 278.14035; IR (cm?1): 3434, 3346, 3214, 2360, 2343, 1592, 1323, 1151, 767, 676. |
Tags: 7745-93-9 synthesis path| 7745-93-9 SDS| 7745-93-9 COA| 7745-93-9 purity| 7745-93-9 application| 7745-93-9 NMR| 7745-93-9 COA| 7745-93-9 structure
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H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
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 |
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