Structure of 53312-82-6
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CAS No. : | 53312-82-6 |
Formula : | C7H5BrN2 |
M.W : | 197.03 |
SMILES Code : | N#CC1=CC=C(N)C=C1Br |
MDL No. : | MFCD03695814 |
InChI Key : | OSYGPHDNNWRFJO-UHFFFAOYSA-N |
Pubchem ID : | 824602 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H315-H319-H332 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.26 |
TPSA ? Topological Polar Surface Area: Calculated from | 49.81 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.67 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.55 |
Solubility | 0.562 mg/ml ; 0.00285 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.31 |
Solubility | 0.966 mg/ml ; 0.0049 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.98 |
Solubility | 0.206 mg/ml ; 0.00104 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) | Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.33 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) | 1.69 |
* 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 |
---|---|---|
49% | To a 40 mL reaction vial with a stir bar are added 2-bromo-4-fluorobenzonitrile (6.00 g, 30.0 mmol) and 3,4,5-trimethoxybenzylamine (5.4 mL, 32 mmol). The reaction is sealed and stirred at 140 C. for 1 hour. The reaction is cooled to room temperature, and CH2Cl2 (15 mL) and trifluoroacetic acid (15 mL) are added. The vial is sealed and the mixture is allowed to stir at room temperature for 24 hours. The reaction is concentrated, diluted with EtOAc (100 mL), washed with saturated aqueous NaHCO3 (2*100 mL), and dried over Na2SO4. The compound is purified by gradient flash chromatography, eluding with 0% to 40% EtOAc in hexanes to yield 4-amino-2-bromobenzonitrile as a tan solid (2.88 g, 49% yield) (LC/MS m/z=197 [M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | at 150℃; for 16h; | To a 40 mL vial with a stir bar are added <strong>[53312-82-6]4-amino-2-bromobenzonitrile</strong> (637 mg, 3.23 mmol), maleic anhydride (317 mg, 3.23 mmol), and cyclohexanone (1.70 mL, 16.2 mmol). The reaction is heated to 150 C. for 16 hours then cooled to room temperature. The product is purified by gradient flash chromatography eluding with 0% to 10% MeOH in CH2Cl2 to provide [1-(3-bromo-4-cyanophenyl)-2-oxo-2,4,5,6,7,7a-hexahydro-1H-indol-3-yl]-acetic acid as a tan solid (456 mg, 38% yield) (LC/MS m/z=375 [M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;bis-triphenylphosphine-palladium(II) chloride; In ethanol; water; toluene; at 80℃; for 19h; | To a stirred mixture of <strong>[53312-82-6]4-amino-2-bromobenzonitrile</strong> (2.00 g, 10.2 mmol), cyclopropyl boronic acid (1,18 g, 13.7 mmol) and K3PO4 (3.23 g, 15.2 mmol) in the mixed solvents of EtOH/H2O/toluene (2 mL/2 mL/12 mL) under nitrogen was added PdCl2(PPh3)2 (0.72 g, 1.03 mmol). This mixture was heated at 800C for 19 h and cooled to room temperature. Next, the mixture was diluted with 150 mL of EtOAc and filtered through a pad of silica gel topped with a layer of celite. This pad was further rinsed with EtOAc (2 x 100 mL). The filtrate was washed with 25 mL of brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude amine. The crude amine was purified by an ISCO auto flash chromatographer using 12O g silica gel column, eluted with hexanes/CH2Cl2 solvents in a 25 min 50% to 100% gradient elution to give 0.75 g of Preparation 4OA as a white solid in 47% yield. [00428] HPLC: 1.55 min (RT) (Chromolith SpeedROD column 4.6 x 50 mm, 10- 90% aqueous MeOH over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z=159 [M+H]+. 1H NMR of 4-amino-2- cyclopropyl-benzonitrile (400 MHz, CDCl3) delta ppm 7.34 (d, J=8.31 Hz, 1 H) 6.44 (dd, J=8.31, 2.27 Hz, 1 H) 6.12 (d, J=2.01 Hz, 1 H) 4.01 (s, 2 H) 2.13-2.24 (m, 1 H) 1.02- 1.12 (m, 2 H) 0.68-0.76 (m, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iron; acetic acid; In ethyl acetate; at 80℃; for 4h; | To a solution of Preparation 66B (8.39 g, 37.12 mmol) in acetic acid (42 mL) and EtOAc (42 mL) maintained at 800C, iron powder (8.3 g, 150.3 mmol) was added with mechanical stirring. The reaction mixture was maintained at 800C until all starting material was consumed (4 h). The reaction mixture was cooled, filtered through Celite and the residue was washed with EtOAc. The filtrate was then neutralized with sat. NaHCtheta3 and the organic layer was washed with water, brine, dried over sodium sulfate, and concentrated in vacuo to yield Preparation 66C (6.5 g) as an off white solid. No purification was necessary. <n="141"/>[00510] HPLC: 4.22 minutes (RT) (Eclipse XDB C18 column, 4.6 x 150 mm eluting with 50-90% aqueous acetonitrile over 15 minutes (0.0 IM ammonium acetate), 1.0 mL/min, monitoring at 280 nm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40 mg CuCI were dissolved in 10 m I water and cooled in an ice bath to 00C. 1.6 ml thionylchloride were added dropwise. The reaction solution was allowed to warm to roomtemperature overnight.1.O g 4-Amino-2-bromo-benzonitrile were suspended in 12 ml hydrochlorc acid and 45 ml water and warmed to 960C until all 4-Amino-2-bromo-benzonitrile were dissolved. The solution was cooled to -5C and 380 mg NaNO2 dissolved in 10 ml water were added. Then the thionlychloride solution was cooled to -2C and added dropwise. The <n="89"/>3-Bromo-4-cyano-benzenesulfonyl chloride precipitated and was collected by filtration and washed with ice cooled water and dried under vacuo to obtain 956 mg 3-Bromo-4- cyano-benzenesulfonyl chloride as a solid. This material was used without further purification. C7H3BrCINO2S (280.53). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In dichloromethane; water; at 20℃; for 3.5h; | 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (2.90 g, 12.8 mmol) was added to a stirred solution of 25 (4.03 g, 12.8 mmol) in CH2Cl2 (85 mL) and H2O (43 mL) at rt. The reaction mixture was stirred for 3.5 h, and then filtered to remove precipitated solids. The filtrate was added to satd NaHCO3 aq, and extracted with CH2Cl2. The organic layer was dried over MgSO4 and concentrated. The resulting residue was purified by silica gel chromatography (hexane/AcOEt = 2/1) to afford 26 (2.13 g, 10.8 mmol, 85%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0℃; for 2h;Reflux; | Di-tert-butyl dicarbonate (Boc2O) (24.6 g, 113 mmol) in THF (75 mL), 4-dimethylaminopyridine (DMAP) (532 mg, 4.35 mmol) and diisopropylethylamine (DIPEA) (35.0 mL, 201 mmol) were added to a solution of 26 (7.70 g, 39.1 mmol) at 0 C. The reaction mixture was refluxed for 2 h, then cooled to rt, and concentrated to about 30 mL H2O and brine were added to it, and the mixture was extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated. The resulting residue was recrystallized from hexane/AcOEt to afford 27 (8.40 g, 21.1 mmol, 54%) as white cubic crystals. The mother liquor was concentrated and the residue was purified by silica gel chromatography (hexane/AcOEt = 6/1) and reprecipitation (from EtOH) to afford 27 (899 mg, 2.26 mmol, 6%) as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In dichloromethane; toluene; at 0℃; for 0.5h; | <strong>[53312-82-6]4-amino-2-bromobenzonitrile</strong> (0.055 g, 0.281 mmol) was stirred in dichloromethane (2 mL) and 0.50 mL saturated sodium bicarbonate solution (0.024 g, 0.281 mmol) solution at 0 C. Phosgene (20% in toluene, 0.3 mL, 0.561 mmol) was added and stirred for 30 min. The organic layer was extracted with dichloromethane and washed with water followed by sodium bicarbonate solution. The organic layer was concentrated and redissolved in DMF (2 mL). 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine (0.050 g, 0.281 mmol) was added and heated at 90 C for 1 h. The resulting solid was filtered and washed with water, ethyl acetate and acetone to yield compound 24 as a pure solid (0.045 g, 0.112 mmol, 40%). See below for characterization data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere; Sealed tube; | To a mixture of <strong>[53312-82-6]4-amino-2-bromobenzonitrile</strong> (1.00 g, 5.08 mmol), 2-ethyl-5,7-dimethyl- 3-(4-(4,4,5,5-tetramethyl-1 ,2-dioxaborolan-2-yl)benzyl)-3H-imidazo[4,5-b]pyridine (OOld, 1.773 g, 4.53 mmol) and K2C03 (2.505 g, 18.13 mmol) was added 1,4-dioxane and 0 (2:1, 30 mL). The reaction mixture was then purged with a stream of N2 for 5 min in a sealable vial before Pd(Ph3P)4 (0.262 g, 0.227 mmol) was added. The reaction vial was sealed and the mixture heated at 100C for 18h. The cooled reaction mixture was then diluted with EtOAc (50 mL), washed with 0 and brine, dried (Na2S04) and evaporated. The crude residue was purified by flash chromatography (ISCO, 0-100% EtOAc-DCM) to afford the title compound (1.46 g, 4.53 mmol, 85%) as a white solid. LC-MS (Method H): 1.220 min, [M + H]+= 382.5; H NMR (400 MHz, CDC13) delta ppm 7.37 - 7.55 (m, 3H), 7.19 (d, / = 8.2 Hz, 2H), 6.90 (s, 1H), 6.51 - 6.68 (m, 2H), 5.51 (s, 2H), 4.17 (br s, 2H), 2.81 (d, / = 7.4 Hz, 2H), 2.59 (s, 3H), 2.64 (s, 3H), 1.33 (t, / = 7.4 Hz, 3H). |
Tags: 53312-82-6 synthesis path| 53312-82-6 SDS| 53312-82-6 COA| 53312-82-6 purity| 53312-82-6 application| 53312-82-6 NMR| 53312-82-6 COA| 53312-82-6 structure
A156769 [263845-82-5]
2-Bromo-4-hydrazinylbenzonitrile
Similarity: 0.88
A156769 [263845-82-5]
2-Bromo-4-hydrazinylbenzonitrile
Similarity: 0.88
A156769 [263845-82-5]
2-Bromo-4-hydrazinylbenzonitrile
Similarity: 0.88
A156769 [263845-82-5]
2-Bromo-4-hydrazinylbenzonitrile
Similarity: 0.88
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Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL