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CAS No. : | 27129-86-8 | MDL No. : | MFCD00013539 |
Formula : | C9H11Br | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QXDHXCVJGBTQMK-UHFFFAOYSA-N |
M.W : | 199.09 | Pubchem ID : | 141334 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 49.21 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.24 cm/s |
Log Po/w (iLOGP) : | 2.57 |
Log Po/w (XLOGP3) : | 3.21 |
Log Po/w (WLOGP) : | 3.05 |
Log Po/w (MLOGP) : | 3.71 |
Log Po/w (SILICOS-IT) : | 3.77 |
Consensus Log Po/w : | 3.26 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.47 |
Solubility : | 0.0667 mg/ml ; 0.000335 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.88 |
Solubility : | 0.261 mg/ml ; 0.00131 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.43 |
Solubility : | 0.00735 mg/ml ; 0.0000369 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.63 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | 3261 |
Hazard Statements: | H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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 |
---|---|---|
78% | With hexamethylenetetramine; water; sodium dodecyl-sulfate; lanthanum(lll) triflate; at 100℃; for 1.5h;Green chemistry; | General procedure: Hexamethylenetetramine 1 (70.1 mg), SDS (3.4 mg) and lanthanum triflate (17.6 mg) were dissolved in water (0.5 mL). Then 1o (271 mg) was added to the flask. The mixture was refluxed for 4 h to complete the reaction, which was monitored by TLC. The reaction mixture was extracted with EtOAc three times and the combined organic phases were distilled under reduced pressure. The crude product was purifiedby column chromatography on silica gel using hexane: EtOAc (5 : 1) as eluent to give 3o, recrystallisation of which from EtOH gave white crystals, 147 mg (71%) (Table 3, entry 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide; In N,N-dimethyl-formamide; at 20℃; | General procedure: Sodium azide (1.2 equiv) was added at room temperature to a solution of bromide derivative (1 equiv, mmol) in DMF (3 mL). The reaction mixture was stirred overnight. Et2O (20 mL) was added to the mixture then the organic layer was washed with water (3 × 20 mL), dried over MgSO4 and concentrated under reduced pressure to give the azide derivative. | |
With sodium azide; sodium iodide; In N,N-dimethyl-formamide; at 40℃; | General procedure: To a DMF solution (3 mL) of bromide derivative, were added sodium iodide (0.05 eq) and sodium azide (1.2 eq) at 40 C. The reaction mixture was stirred for overnight. Et2O (20 mL) was added to the mixture then the organic layer was washed with water (3 × 20 mL), dried over MgSO4 and concentrated under reduced pressure to give the azide derivative. Spectroscopic data of compounds are identical to those previously reported [10]. | |
With sodium azide; In N,N-dimethyl-formamide; at 100℃; for 12h;Inert atmosphere; | The preparation method of the above compound HY034901: Weigh 188 mg (0.94 mmol) of 3,5-dimethylbenzyl bromide in DMF, stir in a reaction flask for 5 min, and add 94 mg (1.45 mmol) of sodium azide solution (DMF solution). ), argon-protected, refluxed at 100 C, stirred for 12 h, and the reaction was completed by TLC. EtOAc was evaporated. It was suction filtered and concentrated to dryness, then EtOAc was dissolved and added to the reaction flask and stirred for 5 min.6.0 mg (0.04 mmol) of isoquinoline-5,8-dione (CH2Cl2) was added dropwise, argon-protected, and stirred under reflux at 25 C for 4 h. The reaction was complete by TLC and terminated. The reaction was concentrated to give a pale yellow crude product. The crude product was separated by an open column (silica gel: 200-300 mesh, column retention volume: 115 ml, elution gradient EtOAc: PE = 25:75). A total of 129 fractions were collected and analyzed by TLC. 1.49 mg of compound HY034901 was obtained. Compound HY034901 is a pale yellow solid powder with brown absorption at 366 nm ultraviolet light. |
With sodium azide; In N,N-dimethyl-formamide; at 100℃; for 12h;Inert atmosphere; | Weigh 210mg (1.06mmol) of 3,5-dimethylbenzyl bromide in DMF, stir for 5min in the reaction bottle, dropwise add 75mg (1.15mmol) of sodium azide solution (DMF dissolved) ), Argon protection, reflux at 100 C, stir the reaction for 12h, complete the reaction by TLC, add pure water, extract with EtOAc, wash the organic phase with water, dry with MgSO4, filter with suction and concentrate to dryness, then dissolve its EtOAc and add dropwise to the reaction flask During stirring for 5 min, 172.3 mg (1.60 mmol) of p-benzoquinone (soluble in EtOAc) was added dropwise, protected by argon, and the reaction was stirred under reflux at 70 C for 24 h. The reaction was detected by TLC, the reaction was terminated, and concentrated to dryness to obtain a tan crude product. The crude product was separated by Combiflash (RediSep Column: Silica 20g, column retention volume was 78ml), and the elution gradient was EtOAc: PE = 25:75. The fractions were analyzed by TLC, combined and concentrated to give 113mg of compound HY052301. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A mixture of anhydrous sodium hydride (5mmol) and 2-nitroaniline (138mg, 1mmol) or 5-chloro-2-nitroaniline (173mg, 1mmol) in DMF (5mL) was stirred for 10min at 0C and then 3,5-dimethylbenzyl bromide (597mg, 3mmol) or 3,5-dimethylbenzensulphonyl chloride (614mg, 3mmol) was added. When the reaction was completed (2-6h) a saturated NaHCO3 aqueous solution was added. The mixture was extracted with dichloromethane (3×10mL) and dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was triturated by treatment with diethyl ether and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS); | EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87%; 7% | With potassium carbonate; In acetone; at 20 - 65℃; | To the suspension of 15 (0.1 mmol) and K2CO3 (0.5 mmol) in acetone (1.0 mL), benzyl bromide (0.3 mmol) was added at room temperature. The reaction mixture was sealed and raised to 65 C. and stirred overnight. After cooled, the reaction mixture was filtered over Celite and washed with EtOAc. After removal of the solvent, the residue was purified by plate chromatography on silica gel (eluent: EtOAc/Petrpleum ether=1:3) to give pure compound 18 and 19 (in some cases, only compound 18 was isolated). 87% yield. 1H NMR: delta 9.45 (d, J=2.0 Hz, 1H), 8.90 (t, J=4.5 Hz, 1H), 8.07 (dd, J=9.5, 2.5 Hz, 1H), 7.56 (s, 1H), 6.99 (s, 2H), 6.94 (s, 1H), 6.62 (d, J=9.5 Hz, 1H), 4.50 (d, J=5.0 Hz, 2H), 3.88 (s, 3H), 2.32 (s, 6H), 1.37 (s, 9H). 13C NMR: delta 151.253, 149.261, 138.623, 138.071, 136.796, 134.385, 129.291, 125.763, 125.477, 124.889, 115.003, 109.970, 103.121, 102.835, 70.417, 47.593, 39.432, 31.205, 28.612, 21.581. LC-MS: (6.75 min, m/z, ES+): calcd: 416.22; Found: 417.19. 7% yield. 1H NMR: delta 8.41 (d, J=2.5 Hz, 1H), 8.17 (dd, J=8.5, 2.5 Hz, 1H), 7.41 (s, 1H), 6.89 (d, J=8.5 Hz, 1H), 6.86 (s, 2H), 6.77 (s, 4H), 4.15 (s, 4H), 3.83 (s, 3H), 2.26 (s, 12H), 1.19 (s, 9H). LC-MS: (6.87 min, m/z, ES+): calcd: 534.30; Found: 535.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; caesium carbonate; In N-methyl-acetamide; ethanol; water; toluene; | EXAMPLE 42 3,5-Dimethylbenzyl (2S)-2-t-butyloxycarbonylamino-3-(1-naphthyl)propionate L-3-(1-Naphthyl)alanine (2 g), di-t-butyldicarbonate (3.0 g) and sodium carbonate (2.5 g) were stirred in a mixture of 1,4-dioxane (12 ml) and water (35 ml) at room temperature for 12 hours. To the solution was added water (100 ml), and the aqueous phase was washed with diethyl ether, acidified to pH3 with solid citric acid, and the product extracted into ethyl acetate. The organic phase was washed with water, dried (MgSO4) and the solvent removed in vacuo to give a solid which was crystallized from ethyl acetate/petroleum ether. This was dissolved in ethanol to which was added a solution of cesium carbonate (0.93 g) in water (10 ml). After the solution had been evaporated to dryness and re-evaporated repeatedly from a toluene solution, dimethylformamide (20 ml) and 3,5-dimethylbenzylbromide (1.3 g) were added. After stirring at room temperature for 16h, the mixture was diluted (water), and the product extracted into ethyl acetate. The organic phase was washed successively with water, 10percent aqueous sodium carbonate, saturated brine and dried (MgSO4). The solvent was removed in vacuo and the residue recrystallized from ethyl acetate/petrol to give the title compound, 0.5 g, mp 93°-94° C. 1 H NMR (360 MHz, CDCl3) delta8.09 (1H, d, J=8 Hz), 7.85 (1H, d, J=7 Hz), 7.75 (1H, d, J=8 Hz), 7.53-7.45 (2H, m), 7.34 (1H, t, J=7 Hz), 7.25 (1H, t, J=9 Hz), 6.93 (1H, s), 6.74 (2H, s), 5.07 (1H, bd, J=7 Hz), 5.00 (1H, d, J=12 Hz), 4.91 (1H, d, J=12 Hz), 4.78-4.76 (1H, m), 3.72-3.47 (2H, m)2.28 (6H, s), 1.40 (9H, s). m/z (CI+) 434 (M+H). Found: C, 74.84; H, 7.30; N, 3.30. C27 H31 NO4 requires C, 74.80; H, 7.21; N, 3.23percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.2% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; | A mixture of 3,5-dimethylbenzyl bromide (1.59 g, 7.986 mmol), 4-bromoaniline (1.374 g, 7.986 mmol), potassium carbonate (5.519 g, 39.93 mmol) and N,N-dimethylformamide (6.5 ml) was stirred at 80 C. for 2 hours under argon atmosphere. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=15:1) to give the title compound (2.106 g, 57.2%) as a pale yellow oil. 1H-NMR (CDCl3) delta: 2.30 (6H, s), 4.00 (1H, brs), 4.20 (2H, s), 6.47-6.53 (2H, m), 6.90-6.98 (3H, m), 7.21-7.26 (2H, m). |
57.2% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;Reflux; | A mixture of 3,5-dimethylbenzyl bromide (1.59 g, 7.986 mmol), 4-bromoaniline (1.374 g, 7.986 mmol), potassium carbonate (5.519 g, 39.93 mmol) and N,N-dimethylformamide (6.5 ml) was stirred at 80 C. for 2 hours under argon atmosphere. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=15) to give the title compound (2.106 g, 57.2%) as a pale yellow oil.1H-NMR (CDCl3) delta: 2.30 (6H, s), 4.00 (1H, brs), 4.20 (2H, s), 6.47-6.53 (2H, m), 6.90-6.98 (3H, m), 7.21-7.26 (2H, m). |
57.2% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;Inert atmosphere; | Example 123: Preparation of the compound 123.; (1) Preparation of the intermediate 123(1).; A mixture of 3,5-dimethylbenzyl bromide (1.59 g, 7.986 mmol), 4-bromoaniline (1.374 g, 7.986 mmol), potassium carbonate (5.519 g, 39.93 mmol) and N,N-dimethylformamide (6.5 ml) was stirred at 80C for 2 hours under argon atmosphere. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane : ethyl acetate = 15:1) to give the title compound (2.106 g, 57.2 %) as a pale yellow oil. 1H-NMR (CDCl3) delta: 2.30 (6H, s), 4.00 (1H, brs), 4.20 (2H, s), 6.47-6.53 (2H, m), 6.90-6.98 (3H, m), 7.21-7.26 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(diethylamino)butylamine; 1-bromomethyl-3,5-dimethylbenzene With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 22h; Stage #2: formic acid In water; acetonitrile HPLC; | 1 Diethyl(3,5-dimethylbenzyl)[bis-(3,5-dimethylbenzyl)aminobutyl]ammonium formate (Compound 28) EXAMPLE 1 Diethyl(3,5-dimethylbenzyl)[bis-(3,5-dimethylbenzyl)aminobutyl]ammonium formate (Compound 28) A mixture of 29 mg (0.2 mmol) of diethylaminobutylamine, 119 mg (0.6 mmol) of 3,5-dimethylbenzyl bromide, and 0.6 mL (0.6 mmol) of 1M NaHCO3, and 2 mL of THF in an 8 mL sealed vial was shaken at room temperature for 22 hr. The reaction product mixture was syringe filtered, and then purified by preparative HPLC using acetonitrile/0.05% aqueous formic acid. Lyophilization of the HPLC fractions gave 48 mg (0.09 mmol) of diethyl(3,5-dimethylbenzyl)[bis-(3,5-dimethylbenzyl)-aminobutyl]-ammonium formate as a gum. 1H NMR (CDCl3): δ1.39 (t, 6H), 1.55 (br m, 2), 1.75 (br m, 2), 2.29 (s,12), 2.31 (s,6), 3.45 (s,4), 4.50 (s,2), 6.88-6.95, (m, 9), and 8.68 ppm (s,1). MS m/z: 499.4 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; for 1h; | As depicted in Scheme 18 above, to a solution of ER-823143-01 (4.00 g, 0.0112 mol) in N,N-dimethylformamide (25 mL) at room temperature was added alpha- bromomesitylene (3.13 g, 0.0157 mol) followed by DBU (4.37 mL, 0.0292 mol). After stirring for 1 hour, reaction was quenched with half-saturated aq. NH4C1, diluted with ethyl acetate, and stirred for Ih to give two clear layers. Organic layer was separated, aq. layer was extracted with ethyl acetate (2x). Combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Crystallization from MTBE afforded ER-824102 (4.30 g, 87%) as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 97℃; | As depicted in Scheme 15 above, a solution of ER-824188-01 (5.7 g, 0.0140 mol), l,8-diazabicyclo[5.4.0]undec-7-ene (4.4 mL, 0.029 mol) and 3,5- dimethylbenzyl bromide (4.7 g, 0.024 mol) in N,N-dimethylformamide (50 mL) was heated at 97 C overnight. An aqueous work-up and purification by flash chromatography provided ER-819762 (4.86 g, 71 %) as colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 20℃; for 1h; | As depicted in Scheme 64 above, to a solution of ER-823143-01 (4.00 g, 0.0112 mol) in N,N-dimethylformamide (25 mL) at room temperature was added alpha-bromomesitylene (3.13 g, 0.0157 mol) followed by DBU (4.37 mL, 0.0292 mol). After stirring for 1 hour, reaction was quenched with half-saturated aq. NH4C1, diluted with ethyl acetate, and stirred for Ih to give two clear layers. Organic layer was separated, aq. layer was extracted with ethyl acetate (2x). Combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Crystallization from MTBE afforded ER-824102 (4.30 g, 87%) as a colorless solid. (BMS-206). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 97℃; | As depicted in Scheme 61 above, a solution of ER-824188-01 (5.7 g, 0.0140 mol), l,8-diazabicyclo[5.4.0]undec-7-ene (4.4 mL, 0.029 mol) and 3,5- dimethylbenzyl bromide (4.7 g, 0.024 mol) in N,N-dimethylformamide (50 mL) was heated at 97 C overnight. An aqueous work-up and purification by flash chromatography provided ER-819762 (4.86 g, 71 %) as colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 1,1‐bis[(4S)‐4‐isopropyl‐4,5‐dihydrooxazol‐2‐yl]ethane With tert.-butyl lithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 1-bromomethyl-3,5-dimethylbenzene In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
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80% | With magnesium; triethylamine; In tetrahydrofuran; for 15h;Reflux; | Example 4Preparation of pinacol ester of 3,5-dimethylbenzylboronic acid In a 2 necks Schlenk type flask, provided with a magnetic stirring bar and topped by a coolant, 3,5-dimethylbenzyl bromide (0.198 g, 1 mmol), pinacolborane (0.128 g, 1 mmol) and triethylamine (59 mg, 1 mmol) are added to 10 ml of a distilled THF solution containing magnesium turnings (24 mg, 1 mmol). The reactive mixture is stirred for approximately 15 hours at THF reflux.At the end of the reaction, the crude reaction product is hydrolyzed by 20 ml of neutral water and is extracted by diethyl ether (3×40 ml). The joined organic phases are washed by 2×50 ml of neutral water then dried on MgSO4. After solvent evaporation, the obtained yield is of 80% with a total conversion of 94% of the starting bromide (yield/conversion of 80%). The resulting boronic ester is analyzed by GC, NMR 1H and 13C and GC/MS.Characterizations:NMR 1H, 6.7 (3H, s); 2.4 (6H, s); 1.8 (2H, s); 1.3 (12H, s).NMR 13C, 139.7; 138.2; 127.9; 83.7; 34.2; 24.9; 21.7.Mass spectrometry: 246-245 (M+, 20-6%); 160 (17%); 147 (29%); 146 (77%); 145 (40%); 131 (24%); 120 (35%); 119 (93%); 118 (16%); 117 (14%); 115 (14%); 106 (15%); 105 (65%); 104 (20%); 103 (19%); 91 (39%); 86 (11%); 85 (82%); 84 (36%); 83 (100%); 79 (14%); 78 (14%); 77 (28%); 59 (28%); 58 (10%); 57 (18%); 55 (19%). |
Yield | Reaction Conditions | Operation in experiment |
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General procedure: To a stirring solution of isatin (1.47 g, 10 mmol) in 20 ml of dryDMF at room temperature sodium hydride (0.40 g, 10 mmol, 60%dispersion in mineral oil) was added portionwise. After the additionthe dark-violet reaction mixture was stirred for 30 min followedby dropwise addition of corresponding alkyl/acylhalogenide (10 mmol) and stirring for 2-8 h. The resulting solutionwas poured into 100 g of crushed ice to form compounds (1, 4-6,8-10) which was filtered off and dried in vacuo (16 Torr). |
Yield | Reaction Conditions | Operation in experiment |
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90% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 80℃; for 2h;Inert atmosphere; | General procedure: To a solution of malononitrile in DMF (30 mL per gram of malononitrile) were added DBU (2.2 equiv) and alkyl halide (2.2 equiv), and the reaction mixture was stirred at 80 C for 2 h. After the reaction was completed, the reaction mixture was cooled to room temperature and water (150 mL per gram of malononitrile) and dichloromethane (150 mL per gram of malononitrile) was added to the reaction mixture. The aqueous layer was extracted with dichloromethane (150 mL per gram of malononitrile) and the combined organic layer was washed with brine, dried over MgSO4, and evaporated. The residue was purified by silica gel chromatography to afford the dialkylated malononitrile. |
Yield | Reaction Conditions | Operation in experiment |
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75% | With potassium carbonate; In acetone; for 6h;Reflux; | 7-[4-(3,5-Dimethyl-benzyloxy)phenylcarbamoyl]heptanoic acid methyl ester (1f). A mixture of 8 (100 mg, 0.36 mmol), 11 (107 mg, 0.54 mmol), and powdered K2CO3 (100 mg, 0.72 mmol) in acetone (10 mL) was refluxed for 6 h. The mixture was cooled to rt and concentrated leaving a residue which was dissolved in ethylacetate and washed with water followed by brine. The organic fractions were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (90:10 ? 80:20, hexanes:EtOAc) to furnish 1f as a white solid (107 mg, 75%). 1H NMR (300 MHz, CDCl3): delta 7.42-6.92 (m, 7H), 4.97 (s, 2H), 3.67 (s, 3H), 3.33 (s, 6H), 3.32 (m, 4H), 1.73-1.62 (m, 4H), 1.40 (m, 4H). 13C NMR (75 MHz, CDCl3): delta 174.2, 171.2, 155.5, 138.1 (2C), 136.7, 131.3, 129.5, 125.3 (2C), 121.6 (2C), 115.0 (2C), 70.3, 51.4, 37.2, 33.9, 28.7, 28.6, 25.4, 24.6, 21.2 (2C). HRMS (ESI) m/z [M+H]+ calcd for C24H32NO4 398.2331, found 398.2337 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h; | General procedure: A stirred solution of 2-aminothiazole 10 or 17 (0.08 g, 0.27 mmol), an appropriately substituted benzyl bromide (11a-ab) (0.03 mL, 0.29 mmol), and Cs2CO3 (0.11 g, 0.35 mmol) in DMF (5 mL) was heated at 120 C for 1 h Yield 31%; mp 225.2 C; Purity by HPLC: 97.68% (35% acetonitrile); 1H NMR (400 MHz, CDCl3): delta 2.31 (s, 6H), 2.38 (s, 3H), 4.44 (d, 2H, J = 4.0 Hz), 5.93 (br s, 1H), 6.95 (s, 1H), 7.00 (s, 2H), 7.03 (dd, 1H, J = 7.6, 0.8 Hz), 7.47-7.49 (m, 2H), 7.53 (t, 1H, J = 7.6 Hz), 7.60 (dd, 1H, J = 9.2, 0.8 Hz), 8.30 (s, 1H), 8.72 (dd, 1H, J = 1.6, 0.8 Hz); 13C NMR (100 MHz, CDCl3) delta 21.50 (2C), 24.45, 50.18, 115.49, 117.63, 120.29, 120.71, 122.93, 125.65 (2C), 128.50, 129.92, 133.15, 136.64, 137.15, 138.77 (2C), 145.78, 149.72, 151.78, 154.51, 158.39, 167.79; IR (KBr) 3228, 3008, 1553 cm-1; HRMS-ESI m/z [M + H]+ calcd. for C24H23N6S: 427.1699, found 427.1699. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium azide; copper(ll) sulfate pentahydrate; sodium L-ascorbate; In water; butan-1-ol; at 66℃; for 24h; | General procedure: The mixture of N-hydroxyhept-6-ynamide (141 mg, 1 mmol), benzyl bromide (256 mg, 1.5 mmol), sodium azide (98 mg, 1.5 mmol), copper(II) sulfate pentahydrate (38 mg, 0.13 mmol), sodium ascorbate (60 mg, 0.3 mmol) in wate and tert-butanol (v/v = 1:1, 10ml) was heated to 66 oC, the heterogeneous mixture was stirred vigrously for 24 h. After addition of water (50 ml), the mixture was filtered. The filter cake was dissloved in MeOH (20 ml), the insolubles was filtered, the filtrate was concentrated in vacuo and crystallized in ethyl acetate to give 2 (156 mg, 57%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
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88% | With potassium tert-butylate; In tetrahydrofuran; for 1h;Reflux; | General procedure: The appropriate cinnamanilide (5.0 mmol), benzyl bromide(0.60 mL, 5.0 mmol) and KtBuO (0.55 g, 5.0 mmol) in THF (100 mL)were stirred and heated under reflux for 1 h. On cooling, the THFwas removed by rotary evaporation and the residue partitionedbetween H2O (50 mL) and EtOAc (100 mL). The EtOAc was separated,washed with brine (50 mL) and dried (MgSO4). Removal ofthe solvent gave the crude N-benzylcinnamanilide, which was eitherrecrystallised from EtOAc/petrol, or purified by column chromatographyon Al2O3, eluting with a solvent gradient from 1:1DCM/petrol to DCM, then recrystallised as before. 4.2.16 N-3,5-Dimethyl-benzyl-N-(4-chlorophenyl)-3-phenylacrylamide (2q) Following the general procedure, N-(4-chlorophenyl)-3-phenylacrylamide 15 1e (1.3 g, 5.0 mmol) was converted to 2q (1.6 g, 88%), Rf (DCM) 0.4; mp 112-113 C; deltaH (500 MHz, CDCl3) 2.26 (6H, s), 4.94 (2H, s), 6.32 (1H, d, J 15.4 Hz), 6.84 (2H, s), 6.88 (1H, s), 7.01 (2H, d, J 8.3 Hz), 7.28-7.36 (7H, m), 7.77 (1H, d, J 15.4 Hz); deltaC (125 MHz, CDCl3) 21.3 (CH3), 53.2 (CH2), 118.5 (CH), 126.4 (CH), 128.0 (CH), 128.8 (CH), 129.2 (CH), 129.7 (CH), 129.8 (CH), 133.6 (C), 135.1 (C), 137.2 (C), 138.1 (C), 140.8 (C), 142.9 (CH), 165.9 (C); numax (solid) 1650, 1614, 1490, 1383, 1318, 1281, 1242, 1199, 1089, 1030, 1011, 847, 763, 732, 700, 680, 563, 541, 521 cm-1; m/z (EI) 377 (16, M+), 375 (44, M+), 247 (18), 245 (56), 131 (100), 119 (44), 103 (41%); HRMS (EI) M+, found 375.1385. C24H22ClNO requires 375.1384. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; In acetone; at 0℃; for 1h; | To a solution of HJC-1-61 (100 mg, 0.43 mmol) and 2C03 (88 mg, 0.64 mmol) in acetone (10 mL) was added l-bromomethyl-3,5-dimethylbenzene (85 mg, 0.43 mmol) at 0 C. The mixture was stirred at 0 C for 1 h. The solution was diluted with EtOAc (100 mL), washed with 1 N HC1 (aq.) (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2S04, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc = 1/1 to 1/3) to give the desired product as a white solid (130 mg, 87%). H NMR (600 MHz, CDC13) delta 7.02 (s, 2H), 6.92 (s, 1H), 4.40 (s, 2H), 3.01-2.97 (m, 1H), 2.30 (s, 6H), 1.88-1.86 (m, 2H), 1.81-1.79 (m, 3H), 1.70- 1.64 (m, 2H), 1.46-1.39 (m, 2H), 1.32-1.26 (m, 1H). 13C NMR (150 MHz, CDCI3) delta 179.9,165.8, 162.9, 138.5 (2C), 135.4, 129.7, 127.0 (2C), 114.0, 94.8, 45.4, 35.4, 30.8 (2C), 25.8, 25.7 (2C), 21.3 (2C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | General procedure: A mixture of anhydrous sodium hydride (5mmol) and 2-nitroaniline (138mg, 1mmol) or 5-chloro-2-nitroaniline (173mg, 1mmol) in DMF (5mL) was stirred for 10min at 0C and then 3,5-dimethylbenzyl bromide (597mg, 3mmol) or 3,5-dimethylbenzensulphonyl chloride (614mg, 3mmol) was added. When the reaction was completed (2-6h) a saturated NaHCO3 aqueous solution was added. The mixture was extracted with dichloromethane (3×10mL) and dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was triturated by treatment with diethyl ether and crystallized from ethanol. | |
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 4h; | General procedure: To a stirred mixture of 2-nitroanilne compound (1.0 eq.) and K2CO3 (1.3 eq.) in dimethylformamide was added dropwise R3CH2Br (1.3 eq.). The reaction mixture was heated to 120 C and stirred for 4 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/hexane) to give desired product 1a. | |
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 4h; | To a stirred mixture of 2-nitroanilne compound (1.0 eq.) and K2CO3 (1.3 eq.) in dimethylformamide was added dropwise R3CH2Br (1.3 eq.). The reaction mixture was heated to 120 C andstirred for 4 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/hexane) to give desired product 1a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium azide; sodium L-ascorbate; at 65℃; for 0.2h;Green chemistry; | General procedure: A mixture of Cu(II)-PsIL (0.2 mol%, 10 mg) and sodium ascor-bate (5 mg) in PEG-400 (2 mL) was allowed to stirrer for 2 min and then, benzyl bromide (1 mmol), sodium azide (1.2 mmol) and alkyl/phenyl acetylene were added to mixture. The reaction mix-ture was stirred at 65C and its progress was monitored by TLC (eluent diethyl ether/ethyl acetate, 2:1). After completion of the reaction, water and ethyl acetate were added; the catalyst was separated by filtration and washed with acetone and water, and dried under vacuum. The organic layer was separated and dried over Na2SO4. The products were purified by recrystallization from n-hexane/EtOAc. |
98% | With sodium azide; sodium L-ascorbate; In ethanol; water; at 85℃; for 0.416667h; | General procedure: A mixture of Cu(II)Br2-BTPTMSP-nSiO2 (0.2 mol%, 10 mg) andsodium ascorbate (5 mg) in ethanol/water (3:1) (2 mL) was stirredfor 2 min and then, benzyl bromide (1 mmol), sodium azide(1.2 mmol) and alkyl/phenyl acetylene (1 mmol) were added to the mixture. The reaction mixture was heated at 85 C. The reaction progress was checked by TLC (eluent n-hexane/ethyl acetate,2:1). At the end of the reaction, the mixture was diluted with waterand ethyl acetate. The catalyst was removed by simple filtration,washed with acetone and water, and dried under vacuum. The organic layer was dried over Na2SO4. The products were purified by recrystallization from n-hexane/EtOAc. |
96% | With sodium azide; C31H38ClCuN2; In water; at 20℃; for 2h; | General procedure: A vial was charged with benzimidazolium salt (1 mmol), sodiumazide (1.05 mmol), alkyne (1.05 mmol), [Cu(NHC)] (3 mol%) andwater (1 ml). The reaction was stirred vigorously at room temperaturefor 2 h. After this time, EtOAc was added and the organicfraction was extracted. The organic extract was dried over MgSO4,filtered and concentrated under reduced pressure to give the expected triazoles. |
96% | With copper(l) iodide; sodium azide; at 20℃; for 0.5h; | 1.0 mmol of phenylacetylene, 1.5 mol of sodium azide, 1.2 mmol of 3,5-dimethylbenzyl bromide, and 0.1 mmol of cuprous iodide were added to 4002.0 mL of polyethylene glycol, and the reaction was stirred at room temperature for 30 min. After the reaction, the product was subjected to column chromatography V petroleum ether: V ethyl acetate = 3: 1 to obtain 1- (3,5-dimethylbenzyl) -4-phenyl1,2,3-triazole. . The product was a white solid. Yield: 96%. |
94% | With sodium azide; CuII(BAPTE)Cl2-[n-Bu4N]4[Mo6O18]2; sodium L-ascorbate; In water; dimethyl sulfoxide; at 20℃; for 1.33333h;Darkness; | General procedure: A mixture of CuII(BAPTE)Cl2-[n-Bu4N]4[Mo6O18]2 (1mol%, 30mg) in H2O/DMSO (3mL, 1:10) was stirred for 10min. Then, the phenylacetylenes (1.3mmol), benzyl halide (1mmol), sodium azide (1.1mmol) and sodium ascorbate (5mol%) were added, and the resulting mixture was stirred at room temperature. The progress of the reaction was monitored by TLC (eluting with n-hexane/ethyl acetate, 1:1). At the end of the reaction, methanol (5mL) was added to precipitate the catalyst. The catalyst was recovered by centrifugation, washed with methanol and diethyl ether, and dried in vaccuo. The filtrates were concentrated and the pure product was obtained by thin layer chromatography. |
96%Chromat. | With sodium azide; (5,6-dimethyl-1,3-bis(2,3,4,5,6-pentamethylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-2-ylidene)copper(I) iodide; In water; at 20℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: A vial was charged with benzimidazolium salt (1mmol), sodium azide (1.05mmol), alkyne (1.05mmol), [Cu(NHC)] (3mol%) and water (1ml). The reaction was stirred vigorously at room temperature for 2h. After this time, EtOAc was added and the organic fraction was extracted. The organic extract was dried over MgSO4, filtered and concentrated under reduced pressure to give the expected triazoles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | General procedure: In a 10mL Schlenk tube (Ra)-4.BH3 (0.35mmol, 1.0equiv) was dissolved in 5mL of THF. After cooling to -78C, tBuLi (0.87mmol, 2.5equiv) was added dropwise and the reaction was slowly warmed to -40C over 2h. After cooling again to -78C the appropriate electrophile (7-10equiv) was added in one portion and the mixture was stirred at room temperature for 16h. The reaction was quenched with 5mL of water and the aqueous phase was extracted with CH2Cl2 (3×3mL). The combined organic layers were dried over Na2SO4, the solvent was evaporated, and the resulting crude mixture was purified by flash chromatography (pentane/CH2Cl2) to afford the desired product as a foamy solid. |
Yield | Reaction Conditions | Operation in experiment |
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72% | General procedure: To a solution of 6-([1,1?-biphenyl]-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives (1.37 mmol) in CH3CN (8 ml), K2CO3 (6.85 mmol) was added and the resulting mixture was stirred for 10-15 min. To this was added the appropriate (bromomethyl)benzene derivatives (1.23 mmol) and the reaction was stirred at room temperature for 16-18 h. Upon completion, the reaction mixture was cooled to ambient temperature and the solvent removed in vacuo. The dried residue was washed by H2O (pH=9-10, 20 mL×2) and brine (15 ml×2) followed by product extraction in ethyl acetate (20 ml). The solvent was evaporated in vacuo to obtain crude product, which was purified using silica gel column chromatography. Same as used for 2a. Yields: 65-70%. 5.2.8.45 4-(4-(Benzyloxy)phenyl)-2-((3,5-dimethylbenzyl)thio)-6-oxo-1,6dihydropyrimidine-5-carbonitrile (8h) Yield 72%; 1H NMR (DMSO-d6): delta 8.00 (d, J = 8.0 Hz, 2H), 7.34 (m, 5H), 7.20 (d, J = 8.0 Hz, 2H), 7.01 (s, 2H), 6.88 (s, 1H), 5.23 (s, 2H), 4.43 (s, 2H), 2.18 (s, 6H); 13C NMR (DMSO-d6): delta 171.5, 170.3, 166.5, 142.7, 141.7, 141.3, 136.0, 134.0, 133.7, 133.2, 133.0, 132.7, 132.0, 121.5, 120.0, 96.9, 74.7, 39.4, 25.9. HRMS (ESI-TOF): Calcd for C27H23N3O2S [MH-]: 452.1433; found: 452.1435. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium carbonate; In N,N-dimethyl-formamide; at 40 - 80℃; for 18h; | To a suspension of ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (lg, 4.60 mmol) and K2C03 (1.20 g, 8.60 mmol) in DMF (7 mL) at 40 C was added 3,5- dimethylbenzyl bromide (3.33 g, 16.75 mmol) dropwise. The reaction mixture wasstirred at 80 C for 18 h. Solvent was removed under reduced pressure and the product purified by flash chromatography using a gradient of 0-20% MeOH in EtOAc to give the title product (850 mg, 55%) as a white powder.HRIVIS m/z (El) 335.15192, calculated for C2,H2,NO3 335.15160; ?H NIVIR (500 IVIHz, CDC13) 8.61 (s, 1H, aromatic), 8.54 (d, J= 8.0, 1H, aromatic), 7.55 (t, J= 7.7,1H, aromatic), 7.39 (t, J= 7.5, 1H, aromatic), 7.34 (d, J= 8.5, 1H, aromatic), 6.94 (s,1H, aromatic), 6.75 (s, 2H, aromatic), 5.32 (s, 2H, Bn-CH2), 4.41 (q, J = 7.1, 2H,CH2CH3), 2.26 (s, 6H 2 x aromatic-CH3), 1.42 (t, J = 7.1, 3H, CH2CH3); ?3C NIVIR(126 IVIFIz, CDC13) 174.56 (CO), 166.08 (CO), 149.96 (aromatic), 139.34(aromatic), 139.20 (aromatic), 134.24 (aromatic), 132.73 (aromatic), 130.32(aromatic), 129.26 (aromatic), 127.93 (aromatic), 125.27 (aromatic), 123.83(aromatic), 116.70 (aromatic), 111.11 (aromatic), 61.10 (Bn-CH2), 57.59 (CH2CH3), 21.36 (aromatic-CH3), 14.52 (CH2CH3). |
Yield | Reaction Conditions | Operation in experiment |
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83% | General procedure: To a mixture of correspondingbromide (1.1 equiv) in 4 mL DMSO was added NaN3 (24 mg, 0.37 mmol).The mixture was stirred at room temperature for 1 h, and the 4mL H2O, sodium ascorbate (29 mg, 0.15 mmol),intermediate 5 (100mg, 0.37 mmol)and CuI (14 mg, 0.07 mmol). The reaction mixture was stirred at roomtemperature overnight, and extracted with ethyl acetate. The extract was driedover anhydrous MgSO4, and concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography with dichloromethane/methanol (10:1) to affordthe desired products 1 and 6-32, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; zinc; In tetrahydrofuran; at 23 - 25℃; for 5h;Irradiation; Inert atmosphere; | General procedure: THF (1.5 mL), organic halide 3 (1.5 mmol, 1.0 equiv) and Ir(dtbbpy)(ppy)2 PF6 (3.5 mg, 0.0025 equiv) were successively added to a test tube containing Zn dust (73 mg, 1.125 mmol, 0.75 equiv). The reaction mixture was stirred under irradiation with a strip of 400 nm LEDs for 5 h, with water cooling to maintain the reaction temperature around 23-25 C. For the work-up, H2O (5 mL) was added and the mixture was extracted with hexane (3 × 7 mL). The combined extracts were filtered through Na2SO4 and concentrated under vacuum.The residue was purified by flash chromatography eluting with hexane/EtOAc. |
Yield | Reaction Conditions | Operation in experiment |
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99% | In tetrahydrofuran; acetonitrile; at 60℃; for 0.166667h; | 5 mmol of trimethylsilylimidazole was dissolved in acetonitrile and diluted to 50 ml of phase A; 10 mmol of 3,5-Dimethyl benzyl bromide dissolved in tetrahydrofuran, diluted to 50ml for the B phase. According to A phase and B phase volume ratio of 1: 1Of the mixture was pumped into the microreactor (sandwichreactorHC), and the reaction was stopped at 60 C for 10 minutes. The microreactorThe material is introduced into a separator and precipitated, filtered and dried to obtain N, N-disubstituted 3,5-dimethylbenzimidazolium salt,The yield was 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.5% | In toluene; at 110℃; for 12h;Inert atmosphere; | Under nitrogen protection,To a 500 mL three-necked flask, 60 g of benzotriazole and 100 mL of toluene were added,Stirring until the benzotriazole is completely dissolved;To the above-mentioned three-necked flask, the solution was slowly added dropwise150g3,5-dimethylbenzyl bromide in toluene60 mL,Refluxed at 110 C for 12 h,After completion of the reaction,The reaction solution was concentrated under reduced pressure,To a volume ratio of 1: 1Dichloromethane and petroleum ether as eluent. The residue was separated by column chromatography,That is to say2- (3 ', 5'-dimethylbenzyl) benzotriazole bromide salt in a yield of 79.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With C38H28O4P2Pd; dihydrogen peroxide; potassium carbonate; In water; at 20℃; for 4h; | The reaction was carried out by adding 3 mmol of 3,5-dimethylbenzyl bromide, 1.2 mmol of phenylboronic acid, 2 mmol of anhydrous potassium carbonate, PEG2000.5.5 mmol and 0.01 mmol of catalyst, 5 ml of pure water and reacting at room temperature for 4 hours in the reaction flask. With about 40ml of ethyl acetate in three extraction, the ethyl acetate organic phase, add 2-3 tablespoons of anhydrous sodium sulfate for 4h in addition to water, filter steaming steam, using TLC method for separation, with (hexane: Methane = 7: 1, v: v) as the developing solvent, and recrystallized from ethanol to give 3,5-dimethyldibenzyl alcohol in a yield of 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.6% | To a stirred suspension of 2-(4-bromo-3-fluorophenyl)-2,4-dihydro-3H-i,2,4- triazol-3-one (0.74 g , 2.87 mmol, 1 equiv) in DMF (15 mL) at 0C under N2 atmosphere,60% NaH (0.138 g, 3.44 mmol, 1.2 equiv) was added portion wise, then stirred for 20 minutes. A solution of 1-(bromomethyl)-3,5-dimethylbenzene (0.628 g, 3.154 mmol, 1.1 equiv) in DMF was added and the reaction mixture was stirred for lh at room temperature. After completion of starting material, the reaction mixture was quenched with ice water, and the solids were filtered off and dried. Purification: Crude compound was washed with n-pentane and dried to get off white solid, 2-(4-bromo-3-fluorophenyl)-4-(3,5- dimethylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one, (0.6 g, 55.6 % yield). LCMS (ES) m/z = 376.1, 378.0 [M+H]. 1H NMR (400 MHz, DMSO-c) O ppm 2.24 (5 , 6 H), 4.78 (5 , 2H), 6.95 (br.s, 3H), 7.73 (d , J = 8.8 Hz, 1 H), 7.79 (t, J = 8.0 Hz, 1 H), 7.90 - 7.87 (m, 1 H), 8.39(s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.5% | Step 3: To a stirred solution of 1-(4-bromo-3-fluorophenyl) imidazolidin-2-one (500 mg, 1.92 mmol) in DMF (8 mL) was added sodium hydride (92 mg, 2.31 mmol, 1.2 equiv) at 0C. The reaction mixture was stirred for 15 min. 1-(bromomethyl)-3, 5-dimethylbenzene (42 mg, 2.12 mmol, 1.1 equiv) in DMF (2 mL) was added drop wise and the reaction mixture was gradually allowed to warm to room temperature and stirred for 4 h. Water was added and the solid was filtered, washed with n-pentane and dried under vacuum to obtain 1-(4-bromo-3-fluorophenyl)-3- (3,5-dimethylbenzyl)imidazolidin-2-one (500 mg, 69.5 %) as off white solid. LCMS (ES) m/z = 377.0, 379.0 [M+H]+. H NMR (400 MHz, DMSO-d6) delta ppm 2.24 (s, 6H), 3.34 (t, J = 8.0 Hz, 2H), 3.79 (t, J = 7.6 Hz, 2H), 4.30 (s, 2H), 6.88 - 6.90 (m, 3H), 7.30 - 7.32 (m, 1 H), 7.58 - 7.62 (m, 1 H), 7.71 - 7.75 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15.99% | With potassium iodide; sodium hydroxide; In dichloromethane; at 20℃; for 15h; | To the 250ml round bottom flask, add <strong>[1115-70-4]metformin hydrochloride</strong> 8g (48.3mmol), dichloromethane 100ml, add 25% sodium hydroxide 40ml, stirring, clarification, adding potassium iodide 3 small particles, and then dropping 3,5-dimethyl bromide Benzyl 4.78 g (24 mmol) was added dropwise over 10 minutes, followed by magnetic stirring at room temperature for 15 hours.The reaction solution was transferred to a separatory funnel and the dichloromethane was separated from the aqueous phase.The aqueous phase was extracted twice with 25 ml of dichloromethane.The dichloromethane solution was combined and evaporated to dryness of dichloromethane to give 2.7 g of crude oil.The crude product was purified by column chromatography on 100-200 mesh silica gel (mobile phase: dichloromethane: methanol = 900: 100).And then reverse phase separation in the middle pressure column, mobile phase: water / acetonitrile = 98/2, pure product target 0.95g.Yield 15.99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium sulfite; In water; for 18h;Reflux; | Step 1. Sodium (3,5-dimethylphenyl)methanesulfonate A solution of 3,5-dimethyl benzyl bromide (1.03 g, 5.17 mmol) and sodium sulfite (0.850 g, 0.674 mmol) in water (8.0 mL) was reflux for 18 h and cooled in ice bath. The white solid was collected by vacuum filtration and washed with cold water to give sodium (3,5-dimethylphenyl)methanesulfonate (0.890 g, 77%). 1H NMR (DMSO-d6, 400 MHz) delta 6.87 (s, 2H), 6.81 (s, 1H), 3.59 (s, 2H), 2.21 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In water; at 100℃; for 2h; | General procedure: The mixture of 4-chloro-2-nitroaniline 6 (1.0mmol) and benzyl bromides 7a, 7b (1.2mmol) in water (4mL) was refluxed at 100C for 2h. After completion of the reaction as monitored by TLC, the reaction mixture was cooled and extracted with ethylacetate. The organic layer was dried over sodium sulphate and concentrated under vaccum. The obtained crude solid was further purified by column chromatography by using ethyl acetate/n-hexane to afford the pure compounds 8a-b. All the synthesized compounds were characterized by 1H NMR and 13C NMR spectroscopy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In N,N-dimethyl-formamide; at 70℃; for 48h; | General procedure: A mixture of 1-(4-adamantylbenzyl)benzimidazole (1 mmol) and 4-alkylbenzylbromide (1.1 mmol) in dimethyl formamide (DMF; 3 mL) was stirred and heated for 2 days at 70 C. Diethyl ether (15 mL) was added to obtain a white crystalline solid which was filtered off. The solid was washed with diethyl ether (3 x 15 mL), and dried under a vacuum to give the title compound 4a (500 mg, 88%) |
89% | In N,N-dimethyl-formamide; for 24h;Heating; | General procedure: A mixture of 1-(4-adamantylbenzyl)benzimidazole (1mmol) and 4-alkylbenzylbromide (1.1mmol) in dimethyl formamide (DMF; 3mL) was stirred and heated for 2days at 70C. Diethyl ether (15mL) was added to obtain a white crystalline solid which was filtered off. The solid was washed with diethyl ether (3×15mL), and dried under a vacuum to give the title compound 4a (500mg, 88%) as white crystals |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.9% | In a 100 ml round bottom flask,Weigh 1.44g (2mmol) of erythromycin A-6,9-9,12-spiroketal,Add 10ml of dichloromethane,Dissolved to clarify,Further, 0.06 g (1 mmol) of potassium hydroxide,0.11 g (1 mmol) of sodium carbonate,TBAB (tetrabutylammonium bromide) 0.32 g (1 mmol),Stir at room temperature for 15-20 minutes,<strong>[27129-86-8]3,5-Dimethylbenzyl bromide</strong> 0.50 g (2.5 mmol) was added to the reaction flask,The reaction was stirred at 45-50 C,TCL detection Erythromycin A-6,9-9,12-spiroketal points disappear after the reaction was stopped,Filtration, the filtrate was washed with saturated sodium bicarbonate solution, washed with water, the solution was evaporated to dryness, medium pressure preparative column was separated, the mobile phase was methanol and water,Obtained target 0.85g, 50.9% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With copper(l) iodide; sodium azide; 1,8-diazabicyclo[5.4.0]undec-7-ene; at 100℃; for 0.75h; | 1.0 mmol of phenylpropyl (Z) -beta-alkenyl bromide,Sodium azide 1.2 mol,3,5-dimethylbenzyl bromide 1.5 mmol,DBU 3.0 mmol,0.2 mmol of cuprous iodide was added to 4003.0 mL of polyethylene glycol,The reaction was stirred at 100 45min,After the reaction product by column chromatography V petroleum ether: V ethyl acetate = 3: 1 after treatment1- (3,5-dimethylbenzyl) -4-phenyl-1,2,3-triazole.The product was a white solid, yield: 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.4% | General procedure: Compound 7a (1.45 g, 3.30 mmol) was dissolved in DMF (10 mL) and then NaH (144 mg, 60% in oil, 3.65 mmol) was added to the mixture at 0 C. The resulting solution was stirred for 50 min at this temperature and 4-methylbenzyl bromide (0.51 mL, 3.65 mmol) was added. The reaction mixture was stirred at room temperature for 8 h. The reaction was quenched by the addition of H2O (30 mL) and the mixture extracted with CH2Cl2 (3×50 mL). The organic layer was dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (silica gel, CH2Cl2/CH3OH = 150:1) to yield compound 8b (1.63g, 90.8%) as yellow oil; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In N,N-dimethyl-formamide; at 70℃; for 48h; | General procedure: 1-(2-Methoxyethyl)benzimidazole (1mmol) was dissolved in DMF (10mL) and then alkyl halide (1.2mmol) was added. The solution was stirred for 2 days at 70C. The precipitated white solid was washed with diethyl ether (3×10mL) and dried under high vacuum. The precipitate was then crystallised from dichloromethane-diethyl ether to give the title compounds as white crystals. |
89% | In N,N-dimethyl-formamide; at 70℃; | General procedure: For the preparation of benzimidazolium salts 1a-d and 2a-e., 1-(2-Methoxyethyl)benzimidazole (1 mmol) was dissolved in anhydrous dimethylformamide (DMF), (3mL) and alkyl halide (1.2mmol) was added at room temperature. The reaction mixture was stirred at 70C for 48h. After completion of the reaction, the DMF was removed by vacuum and diethyl ether (15mL) was added to obtain a white crystalline solid, which was filtered off. The solid was washed with diethyl ether (3×10mL) and dried under vacuum. The crude product was recrystallized from dichloromethane-diethyl ether and completely dried under vacuum to give the title compounds as white crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In N,N-dimethyl-formamide; at 70℃; for 48h; | General procedure: 1-(2-Methoxyethyl)benzimidazole (1mmol) was dissolved in DMF (10mL) and then alkyl halide (1.2mmol) was added. The solution was stirred for 2 days at 70C. The precipitated white solid was washed with diethyl ether (3×10mL) and dried under high vacuum. The precipitate was then crystallised from dichloromethane-diethyl ether to give the title compounds as white crystals. |
92% | In N,N-dimethyl-formamide; at 70℃; | General procedure: For the preparation of benzimidazolium salts 1a-d and 2a-e., 1-(2-Methoxyethyl)benzimidazole (1 mmol) was dissolved in anhydrous dimethylformamide (DMF), (3mL) and alkyl halide (1.2mmol) was added at room temperature. The reaction mixture was stirred at 70C for 48h. After completion of the reaction, the DMF was removed by vacuum and diethyl ether (15mL) was added to obtain a white crystalline solid, which was filtered off. The solid was washed with diethyl ether (3×10mL) and dried under vacuum. The crude product was recrystallized from dichloromethane-diethyl ether and completely dried under vacuum to give the title compounds as white crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triethylamine; In acetonitrile; for 8h;Reflux; | General procedure: To a stirred solution of 3 (100 mg, 0.28 mmol) in 5 mLDCM was added excessive amount of CF3CO2H dropwiseunder nitrogen at 0 C, and the reaction was monitored byTLC. The solvent was removed under reduced pressure toyield de-protection product as light yellow oil, which wasused in next step without further purification.Corresponding bromide (1 equiv) was added to a solutionof above obtained oil and triethylamine (150 muL) inacetonitrile (5 mL) and the reaction mixture was stirredunder reflux for 8 h. Subsequently, the solvent was evaporatedunder reduced pressure to get residue, which waspurified by silica gel column chromatography to afford thedesired products 4a-4u, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In N,N-dimethyl acetamide; at 20℃; for 18h;Sealed tube; | Toward a sealed tube (25 mL) was added with perfluoro-2-methyl-2-pentanol potassium 2 (3.93 g, 10.5 mmol), compound 4 (10 mmol) and anhydrous DMAc (10 mL), the mixture was sealed and stirred at room temperature for 24 h. After the reaction was completed, the mixture was extracted by ether, which was washed by DI-water and saturated brine for several times. The organic phase was dried by sodium sulfate and the solvent was removed. The product was obtained by column chromatography (EtOAc: petroleum=1:40). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In N,N-dimethyl-formamide; at 70℃;Inert atmosphere; Schlenk technique; | General procedure: A mixture of benzimidazolium salt 1a-e (1 mmol) and the corresponding benzyl bromide orchloride (1 mmol) in (2 ml) was stirred at 70C for 2-3 days. The white solid formed was filtredthrough filter paper and washed with diethyl ether (2*10 ml). The white solid was crystallizedwith DCM-ether (1:3). |
In N,N-dimethyl-formamide;Heating; Inert atmosphere; Schlenk technique; | General procedure: To a solution of 5,6-dimethylbenzimidazole (3 mmol, 4.38 g) in EtOH (25 mL), KOH(4 mmol, 2.5 g) was added and the reaction mixture was stirred for 15 min at roomtemperature. The corresponding aryl chlorides or bromides (3 mmol, 6 g) were added slowly and the resulting mixture was heated for 8 h at 50 C. The solids that formedwere washed with diethyl ether (310 mL) and the corresponding benzimidazoliumsalt was obtained in 86-96% yield after drying under vacuum (Figure 1). Details for1a-1f are provided in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | General procedure: Benzyl acrylate (2a), methyl acrylate (2k), ethyl acrylate (2l), butyl acrylate (2m), isobutyl acrylate (2n), and tert-butyl acrylate (2o) were obtained from TCI or Aldrich, and were used as supplied. The other acrylates were synthesized by a modification of the reported procedure as follows.2 A 100 mL round-bottom flask equipped with a stirring bar was charged with K2CO3 (1660 mg, 12.0 mmol) and DMF (20 mL). To the solution, acrylic acid (820 muL, 12.0 mmol) was added at 0 C and the reaction was allowed to stir at 0 C for 1 h. To the mixture, corresponding alkyl halide (10.0 mmol) was added and the mixture was stirred at the indicated temperature. To the reaction mixture, brine was added, and the mixture was extracted with CH2Cl2 (3 * 25 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The remaining residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford the desired acrylate 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Compound 1 (10 mmol), anhydrous potassium carbonate (20 mmol, K2CO3) and DMF (20 mL) were added to a 100 mL-dry eggplant flask and stirred at room temperature for 30 min prior to addition of p-bromobenzyl bromide (12 mmol). The resulting mixture was maintained at 80 C for 3-8 h, and the reaction course was monitored using TLC. Upon the reaction completion, the mixture was cooled to room temperature before the addition of 100mL of water, and the system was extracted with ethyl acetate (30 mL 3). The organic phase was dried over anhydrous Na2SO4 and concentrated using rotary evaporator. The crude product 2 was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In N,N-dimethyl-formamide; at 100℃;Sealed tube; | To a stirred solution of 5-bromo-4-fluoro-2H-indazole (0.65g, 3.023mmol, 1 equiv), in DMF (15 mL) was added 1 -(bromomethyl)-3,5-difluorobenzene (0.75 g, 3.627mmol, 1 .2equiv) at room temperature. The reaction mixture was heated to 100C and stirred for overnight in a sealed tube. The reaction mixture was cooled to room temperature, quenched with ice water basified with sat NaHC03 and extracted with EtOAc. The organic layer was dried over Na2S04, and concentrated to obtain crude product. The crude product was purified by flash column chromatography (100 - 200 Silicagel, 12g pack) using10% EtOAc in Hexane as mobile phase to afford the desired product 5-bromo-2-(3,5- difluorobenzyl)-4-fluoro-2H-indazole (0.8 g, 80%) as a light yellow solid. LC-MS (ES) m/z = 341 .0, 343.0 [M+H]+. NMR (400 MHz, DMSO-d6) delta ppm 5.68 (s, 2 H), 7.06 (d, J = 6.4 Hz, 2 H),7.18 (t, J = 9.2 Hz, 1 H), 7.36 - 7.40 (m, 1 H), 7.43 - 7.45 (m, 1 H), 8.78 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A solution of benzo[d]thiazol-2-ol (3.0 mmol), anhydrous K2CO3 (3.0 mmol) and 5 mL DMF was stirred in a round-bottomed flask for 1 h at 60 C, then, 1.2 mmol of alkyl bromide or substituted brominated benzyl compound was added slowly to the reaction solution. The reaction solution was refluxed for 5 h, the reaction was monitored by TLC. DMF was evaporated under reduced pressure,the residue was washed with water, filtered, dried and the crude product was crystallized from MeOH.The yield, melting point, and spectral data of each compound are given below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With copper(l) iodide; sodium azide; potassium carbonate; at 60℃; for 0.75h; | 1.0 mmol of phenylpropynic acid, 1.5 mol of sodium azide, 1.2 mmol of 3,5-dimethylbenzyl bromide, 0.2 mmol of potassium carbonate,0.1mmol of cuprous iodide was added to 4003.0mL of polyethylene glycol, and the reaction was stirred at 60 C for 45min.After the reaction, the product was subjected to column chromatography V petroleum ether: V ethyl acetate = 3: 1 to obtain1- (3,5-dimethylbenzyl) -4-phenyl-1,2,3-triazole. The product was a white solid, yield: 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydride; at 0℃; for 5h; | General procedure: A stirred solution of 3-chloro-1H-indole-4-carboxylate (700 mg, 4 mmol) in THF (20 mL) was added NaH (60%, 240 mg, 6mmol) slowly at 0 oC. Then substituted benzyl bromide (4.4 mmol) was added to the mixture and stirred for 5 h. After the reaction was completed monitored by TLC, H2O (20 mL) was added slowly to quench the reaction and extracted with ethyl acetate (150 mL × 3). The combined organic phase was washed by brine (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to get a white solid. The product was used in the following steps without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene at -10℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: bis((S)-4-benzyl-4,5-dihydrooxazol-2-yl)methane With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Schlenk technique; Inert atmosphere; Stage #2: 1-bromomethyl-3,5-dimethylbenzene In tetrahydrofuran Schlenk technique; Inert atmosphere; |
Tags: 27129-86-8 synthesis path| 27129-86-8 SDS| 27129-86-8 COA| 27129-86-8 purity| 27129-86-8 application| 27129-86-8 NMR| 27129-86-8 COA| 27129-86-8 structure
[ 81093-21-2 ]
1-(Bromomethyl)-2,3-dimethylbenzene
Similarity: 0.96
[ 4761-00-6 ]
2-(Bromomethyl)-1,3,5-trimethylbenzene
Similarity: 0.92
[ 21988-87-4 ]
1,3,5-Tris(bromomethyl)-2,4,6-trimethylbenzene
Similarity: 0.92
[ 15442-91-8 ]
1,2,4,5-Tetrakis(bromomethyl)benzene
Similarity: 0.92
[ 81093-21-2 ]
1-(Bromomethyl)-2,3-dimethylbenzene
Similarity: 0.96
[ 4761-00-6 ]
2-(Bromomethyl)-1,3,5-trimethylbenzene
Similarity: 0.92
[ 21988-87-4 ]
1,3,5-Tris(bromomethyl)-2,4,6-trimethylbenzene
Similarity: 0.92
[ 15442-91-8 ]
1,2,4,5-Tetrakis(bromomethyl)benzene
Similarity: 0.92
[ 81093-21-2 ]
1-(Bromomethyl)-2,3-dimethylbenzene
Similarity: 0.96
[ 4761-00-6 ]
2-(Bromomethyl)-1,3,5-trimethylbenzene
Similarity: 0.92
[ 21988-87-4 ]
1,3,5-Tris(bromomethyl)-2,4,6-trimethylbenzene
Similarity: 0.92
[ 15442-91-8 ]
1,2,4,5-Tetrakis(bromomethyl)benzene
Similarity: 0.92
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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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