Structure of 27710-82-3
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CAS No. : | 27710-82-3 |
Formula : | C23H28Br2NP |
M.W : | 509.26 |
SMILES Code : | CN(CCC[P+](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)C.[H]Br.[Br-] |
MDL No. : | MFCD00077740 |
InChI Key : | NEQVFHFOWYYPBS-UHFFFAOYSA-M |
Pubchem ID : | 23651404 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 27 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 132.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
16.83 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
6.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.89 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.83 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-7.41 |
Solubility | 0.0000197 mg/ml ; 0.0000000386 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-7.13 |
Solubility | 0.000038 mg/ml ; 0.0000000746 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-8.83 |
Solubility | 0.000000752 mg/ml ; 0.0000000015 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
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 |
-4.46 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
2.0 |
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 |
0.17 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.88 |
* 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 |
---|---|---|
82% | at 20 - 100℃; Sealed tube | Preparation of (3-(Dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt. To a suspension of 3-bromopropyltriphenylphosphonium bromide (1.0 g, 2.1 mmol) in ethanol (5 mL) was added a solution of 40percent dimethylamine in water (3 mL) at room temperature. The mixture was stirred and heated at 100 °C for 30 min in a sealed microwave tube. After the reaction mixture was concentrated under reduced pressure, the solid residue was recrystallized in acetonitrile to afford (3- (dimethylamino)propyl)triphenylphosphonium bromide hydrobromide salt (0.90 g, 82percent) as a white solid, and was used in the following step. ESI MS m/z 348.3(Ph3PCH2CH2CH2NMe2)+. |
74.2% | Stage #1: at 20℃; for 1.5 h; Heating / reflux Stage #2: With Acetyl bromide In ethanol at 0 - 25℃; |
Example 4; Synthesis of the Wittig Reagent 3-dimethylaminopropyltriphenylphosphonium Bromide *HBr (Olo-IM4) To a stirred suspension of 3-bromopropyltriphenylphosphonium bromide (Olo-IM3) (420 g, 0.90 mol) in absolute ethanol (664 g) a solution of dimethylamine in absolute ethanol (368 g, 2.69 mol, assay: 33percent) was added slowly within 30 minutes at room temperature. After complete addition the suspension was stirred 1 hour at reflux whereupon a solution was obtained. The solution was cooled to a temperature of 0-10° C. and acetyl bromide (202.7 g, 1.65 mol) was added dropwise until the pH was 1, and the resulting suspension was allowed to warm to 20-25° C. After the white suspension was filtered the wet product washed with absolute ethanol (237 g) and then dried under vacuum (15 h, 70° C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a white solid (yield: 471.2 g, 0.77 mol, 85.1percent; HPLC assay: 83.2percent, HPLC purity: 98.72percent). The crude material (460 g, 0.75 mol; assay: 83.2percent) was further purified by suspending it in absolute ethanol (395 g) and stirring at reflux temperature. After addition of further absolute ethanol (435 g) all material was dissolved and the solution was allowed to cool to room temperature, with seeding at 69° C. to initiate crystallization. After 4 hours stirring at room temperature the product was filtered off, washed with ethanol (140 g) and then dried under vacuum (15 h, 70° C.) to give 3-dimethylaminopropyltriphenylphosphonium bromide*HBr (Olo-IM4) as a crystalline white solid (yield: 333.7 g, 0.66 mol, 87.2percent; HPLC assay >99.9percent, HPLC purity: 99.85percent, overall yield: 74.2percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In tetrahydrofuran; methanol; diethyl ether; water; | EXAMPLE 9 Methyl 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetate (Compound 18) In this example, 48 g of (3-dimethylaminopropyl)-triphenylphosphonium bromide hydrobromide is suspended in 200 ml of tetrahydrofuran under a nitrogen atmosphere and 80 ml of 1.6N-n-butyl lithium hexane solution is added thereto under ice-cooling. The mixture is stirred under ice-cooling for one hour. A solution obtained by dissolving 5.0 g of 11-oxo-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid in 120 ml of tetrahydrofuran is dropwise added under ice-cooling. After stirring the mixture at room temperature for two hours, the solvent is distilled away under reduced pressure. Then, 200 ml of water is added to the residue and the mixture is washed with 200 ml of diethyl ether. The pH of the mixture is adjusted to 1 with aqueous 4N-hydrochloric acid solution and the mixture is washed with diethyl ether. Then, aqueous 10N-sodium hydrooxide solution is added thereto to adjust the pH of the mixture to 7 and the solvent is distilled away under reduced pressure. The resultant residue is dissolved in 400 ml of methanol and 5 g of p-toluene sulfonic acid is added thereto. After heating the mixture at reflux for two hours, the solvent is distilled away under reduced pressure. The residue is extracted with 300 ml of ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution in order and dried over anhydrous sodium sulfate. The solvent is distilled away under reduced pressure and the resultant residue is purified by column chromatography on silica gel (eluent: hexane:ethyl acetate:triethylamine=10:10:1) to obtain 4.0 g of the desired product as a colorless oily matter. Cis form NMR (CDClc, delta, ppm): 2.06-2.67(m, 4H), 2.16(s, 6H), 3.46(s, 2H), 3.58(s, 3H), 5.08(bs, 2H), 5.69 (t, 1H, J=7Hz), 6.53-7.30(m, 7H) Trans form NMR (CDCl3, delta, ppm): 2.06-2.67(m, 4H), 2.16(s, 6H), 3.46(s, 2H), 3.58(s, 3H), 5.08(bs, 2H), 6.06 (t, 1H, J=7Hz), 6.53-7.30(m, 7H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 3; Preparation of Olopatadine Hydrochloride Form A Through Wittig Reaction Using Sodium Hydride3-[bromo(triphenyl)phosphoranyl]-N,N-dimethyl propan-1-amine hydrobromide (phosphonium salt) (205 g; 0.40 mol) was suspended in 545.5 g (615 mL) of tetrahydrofuran under a nitrogen atmosphere. After stirring for 40 minutes, 64.48 g (1.61 mol) of sodium hydride 60percent in mineral oil was added over five minutes. After addition of the sodium hydride, the reaction mixture was heated to reflux (approximately 65° C.) with continuous stirring and maintained at this temperature for 1 hour. An intense orange suspension was obtained. The reactor contents were then cooled to room temperature and 36 g (0.13 mol) of (11-oxo-6,1'-dihydrodibenzo[b,e]oxepin-2-yl)acetic acid (Compound II, R1H) was added with stirring. The mixture was then stirred for 15 hours at room temperature.Thereafter, a mixture of 153.5 g (153.5 mL) of deionized water and 136.1 g (153.5 mL) of tetrahydrofuran was slowly added with continuous stirring. Next, 615 g (615 mL) of deionized water was added, and stirring was continued for 20 minutes. The resulting two phase mixture was then acidified with hydrochloric acid (37percent) with stirring to adjust the pH to approximately 3 (actual reading 2.27). The aqueous and organic phases were then separated, and the aqueous phase was salified with 180 g of sodium chloride and extracted with 607.5 g (750 mL) of 1-butanol. The phases were then separated, and the organic phase was washed three times with water.The solvent of the organic phase was then removed by distillation under reduced pressure to yield 119.61 g of an orange oil. To this oil was added 157 g (200 mL) of 2-propanol, which produced a yellow suspension. The mixture was then stirred and maintained at this temperature for 1 hour. Thereafter, the suspension was filtered, and the collected wet solid was dried under vacuum at 60° C. until constant weight to yield 37.23 g (0.10 mol, 74.21percent) of olopatadine hydrochloride. (HPLC Purity: 54.28percent, cis: 6.44percent, trans; Cis/Trans Ratio: 8.43).A 36 g portion of the olopatadine hydrochloride obtained was then suspended in 226.08 g (288 mL) of 2-propanol. The mixture was heated to reflux (approximately 82° C.) with continuous stirring and maintained at this temperature for a minimum 20 minutes. The reactor was then cooled to room temperature, and the suspension was filtered to yield a slight yellow solid that was dried under vacuum at 60° C. (Partial Yield 37.62percent; HPLC Purity: 97.23percent cis, 0.76percent trans; Cis/Trans Ratio: 128. 50).A 17 g portion of the olopatadine hydrochloride obtained in the previous step was then treated with 120.1 g (153 mL) of 2-propanol. The white to white off suspension obtained was stirred and heated to reflux for 55 minutes. Then, it was allowed to cool to room temperature. The suspension was then filtered, and the solid was washed with 2-propanol and dried under vacuum at 60° C. (Partial Yield 35.67percent; HPLC Purity: 99.56percent cis, 0.18percent trans; Cis/Trans Ratio: 538.54).A 15 g portion of the olopatadine hydrochloride obtained in the previous step was then treated with 58.8 g (75 mL) of 2-propanol. The resulting white suspension was stirred and heated to reflux for 30 minutes. Thereafter, the reactor content was cooled to room temperature. The white suspension was then filtered, and the solid was washed with 2-propanol and dried under vacuum at 60° C. to yield 14.42 g of olopatadine hydrochloride. (Global Yield 34.29percent; HPLC Purity: 99.73percent cis; 0.10percent trans; Cis/Trans Ratio: 760.46).A 10 g portion of the olopatadine hydrochloride obtained in the previous step was treated with a mixture of 23.5 g (30 mL) of 2-propanol and 15 g of deionized water. The resulting white suspension was stirred and heated to reflux for 15 minutes. Thereafter, the reactor content was cooled to room temperature. The white suspension was then filtered, and the solid was washed with 2-propanol and dried under vacuum at 60° C. to yield 7.49 g of olopatadine hydrochloride. (Global Yield 25.68percent; HPLC Purity: 99.98percent cis; 0.02percent trans; Cis/Trans Ratio: 4999.35).A 6.7 g portion of the olopatadine hydrochloride obtained in the previous step was treated with a mixture of 15.8 g (20 mL) of 2-propanol and 10 g of deionized water. The resulting white suspension was then stirred and heated to reflux for 10 minutes. Thereafter, the reactor content was cooled to room temperature. The white suspension was then filtered, and the solid was washed with 2-propanol and dried under vacuum at 60° C. to yield 3.44 g of olopatadine hydrochloride Form A. (Global Yield 13.18percent; HPLC Purity: 99.91percent cis, 0.01percent trans; Cis/Trans Ratio: 11708.08).Analytical data: HPLC purity: 99.91percent; Assay: 101.62percent; XRD (2psi): 6.33°, 10.92°, 12.66°, 15.44°, 17.60°, 18.30°, 19.04°, 19.34°; 20.61°, 24.08°, 25.45°, 28.34° (substantially identical to FIG. 1); ... | ||
Example-1: Preparation of ll-[(Z)-3-(dimethylamino)propylidene]-6-ll-dihydro dibenz[b,e] oxepin-2-aceticacid hydrochloride compound of formula-lan-Butyl lithium (100 ml) was added to the solution of 3-dimethylaminopropyl)- triphenyl phosphoniumbromide HBr compound of formula-3 (37.94 grams) in tetrahydrofuran (200 ml) at 0-5 °C under nitrogen atmosphere. The reaction mixture was stirred for an hour at the same temperature. A mixture of l l-oxo-6, 11-dihydrobenz (b,e)oxepin-2-acetic acid compound of formula-2 (10 grams) and tetrahydrofuran (30 ml) was added to the reaction mixture at 0-5°C. Slowly raised the temperature of the reaction mixture to 65-70°C and then hated to reflux. The reaction mixture was stirred for 12 hours at 65-70°C. After completion of the reaction, the reaction mixture was cooled to 5-10°C. The reaction mixture was quenched with aqueous hydrochloric acid at 5-10°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for an hour. Both organic and aqueous layers were separated. The aqueous layer was washed with toluene and then the aqueous layer was neutralizing with aqueous sodium carbonate solution at 5-10°C. The reaction mixture was washed with ethyl acetate. Hydrochloric acid (20 ml) and acetic acid (40 ml) was added to the reaction mixture at 25-30°C. The reaction mixture was stirred for 15 minutes and then dichloromethane was added to it. Both organic and aqueous layers were separated. The organic layer was washed with brine solution and the organic layer was distilled off under reduced pressure. Acetone (100 ml) was added to the residue at 25-30°C and stirred the reaction mixture for 45 minutes at 25-30°C. The solid was filtered, washed with acetone and dried to get the title compound. Yield: 5 grams,M.P: 238-241°C (Decomposition)Purity by HPLC: 97.7percent (Z-isomer), 1.15percent (E-isomer) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.63% | To the 50L dry reaction kettle without adding water treatment of tetrahydrofuran 24L, dimethyl sulfoxide 900ml, water bath cold1.64 kg (41.0 mol) of sodium hydride (60percent) was added with stirring, and triphenylphosphonium bromide (3-dimethylaminopropyl) hydrobromide(16.0 mol) were added, and the mixture was stirred at room temperature for 1.5 to 2 hours. The temperature was raised to 45 ° C and reacted for 1.5 hours. Cool to 20 & lt; 0 & gt; C and add <strong>[55453-87-7]Isoxepac</strong> Acid (2.15 g, 8.0 mol) at room temperature for 10 to 12 hours. The reaction was complete by TLC. The mixture was cooled to 10 to 15 ° C, and water and tetrahydrofuran solution (water: 0.8 L, THF: 2.0 L) was added dropwise thereto over about 1 hour.Stirred for 30 minutes, filtered, and the filter cake rinsed with 1 L of THF. The filtrate was combined, concentrated hydrochloric acid was added with stirring to pH ~ 3, and stirring was continued for 30 minutesClock, filter. The filter cake was washed with 2 L of tetrahydrofuran and allowed to dry. The solid was transferred to a reaction vessel, 12 L of water was added and the pH was adjusted with 10 N sodium hydroxide(About 65 ° C), stirred for 5 hours at 5 to 10 ° C, and filtered. The solids were then washed 3 L x 2 in deionized waterTimes, drained. 80 degrees for 2 hours in the blast drying dry olorotatin 1.5kg. Purity 98.72percent (HPLC), Isomer: 0.48percent(HPLC), Yield: 55.63percent |
Tags: 27710-82-3 synthesis path| 27710-82-3 SDS| 27710-82-3 COA| 27710-82-3 purity| 27710-82-3 application| 27710-82-3 NMR| 27710-82-3 COA| 27710-82-3 structure
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P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
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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