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CAS No. : | 590-17-0 |
Formula : | C2H2BrN |
M.W : | 119.95 |
SMILES Code : | N#CCBr |
MDL No. : | MFCD00001884 |
InChI Key : | REXUYBKPWIPONM-UHFFFAOYSA-N |
Pubchem ID : | 11534 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H226-H301+H311+H331-H315-H319-H335 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P261-P264-P270-P271-P280-P301+P310+P330-P303+P361+P353-P304+P340+P311-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 6.1(3) |
UN#: | 3275 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
2.6 g | With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane for 12 h; Cooling with ice | A) 1-tert-butyl 4-ethyl 4-(cyanomethyl)piperidine-1,4-dicarboxylate To a mixture of diisopropylamine (4.7 g) and THF (75 mL) was added n-butyllithium hexane solution (1.6 M, 29 mL) under ice-cooling, and the mixture was stirred for 30 min. To the mixture was added a mixture of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (6.0 g) and THF (10 mL) under ice-cooling, the mixture was stirred under ice-cooling for 3 hr, and 2-bromoacetonitrile (5.6 g) was added thereto under ice-cooling. The mixture was stirred for 12 hr, and the solvent was evaporated under reduced pressure. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.6 g). 1H NMR (300 MHz, DMSO-d6) δ 1.21 (3H, t, J = 7.0 Hz), 1.39 (9H, s), 1.43-1.54 (2H, m), 1.90-2.00 (2H, m), 2.87 (2H, s), 2.96-3.12 (2H, m), 3.57-3.67 (2H, m), 4.11-4.22 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | potassium carbonate; In acetone; | EXAMPLE 27 2-Hydroxyphenethyl alcohol was reacted with bromoacetonitrile in the presence of potassium carbonate to protect the phenolic oxygen, as in Tetrahedron Letters, 1993, 34, 7567-7568. 2-Hydroxyphenethyl alcohol was dissolved in 20 mL acetone. To this was added 1.2 g potassium carbonate. To the stirring mixture was added 0.87 g bromoacetonitrile under nitrogen. The mixture was stirred overnight. The mixture was filtered, and the filtrate was concentrated. The product was purified by flash column chromatography on silica gel, eluding with 1/1 ethyl acetate:hexanes, to yield 81percent of 2-(o-cyanomethyl)phenethyl alcohol. 1H NMR (CD2Cl2): 2.81 (t, 2H), 3.72 (t, 2H), 4.77 (s, 2H), 6.92 (dd, 2H), 7.18 (d, 2H). |
81% | With potassium carbonate; In acetone; | 2-Hydroxyphenethyl alcohol was reacted with bromoacetonitrile in the presence of potassium carbonate to protect the phenolic oxygen, as in Tetrahedron Letters,1993, 34, 7567-7568. 2-Hydroxyphenethyl alcohol was dissolved in 20 mL acetone. To this was added 1.2 g potassium carbonate. To the stirring mixture was added 0.87 g bromoacetonitrile under nitrogen. The mixture was stirred overnight. The mixture was filtered, and the filtrate was concentrated. The product was purified by flash column chromatography on silica gel, eluting with 1/1 ethyl acetate:hexanes, to yield 81percent of 2-(o-cyanomethyl)phenethyl alcohol.1H NMR (CD2Cl2): 2.81 (t, 2H), 3.72 (t, 2H), 4.77 (s, 2H), 6.92 (dd, 2H), 7.18 (d, 2H). 2-(o-Cyanomethyl)phenethyl alcohol (1.0 g, 6.3 mmol) was dissolved in 5 mL anhydrous DMF and added to a stirring solution of sodium hydride (0.25g, 10.4 mmol) in DMF (20 mL). After hydrogen evolution ceases, methyl iodide (0.47 mL, 7.5 mmol) was added dropwise. The mixture was stirred at room temperature under nitrogen for five hours. After aqueous workup, the product was purified using flash column chromatography on silica gel, eluting with 1/5 ethyl acetate/hexanes solvent mixture to yield 0.56 g (56percent) of the desired product, 2-(o-cyanomethyl)phenethyl methyl ether. 1H NMR (CD2Cl2): 2.96 (t, 2H), 3.36 (s, 3H), 3.60 (t, 2H), 4.86 (s, 2H), 7.04 (dd, 2H), 7.31 (d, 2H). 2-(o-Cyanomethyl)phenethyl methyl ether was deprotected following the procedure described in Tetrahedron Letters, 1993, 34, 7567-7568. 2-(o-Cyanomethyl)phenethyl methyl (0.56 g, 3.13 mmol) was dissolved in 40 mL anhydrous ethanol. Platinum dioxide (20 mg) was added to this solution. The solution was purged with hydrogen for 10 minutes, and then stirred under hydrogen overnight. The mixture was filtered, and the filtrate was concentrated. The residue was redissolved in ether, washed with water, and dried over MgSO4. After concentration, 0.39 g (82percent) of 2-hydroxyphenethyl methyl ether was isolated. 1H NMR (CD2Cl2): 2.78 (t, 2H), 3.32 (s, 3H), 3.60 (t, 2H), 2-Hydroxyphenethyl methyl ether was reacted with diethylphosphoramidous dichloride to yield the corresponding phosphorous amidite in the same manner as described for Example 25. 31P NMR (toluene): 137 ppm. The phosphoroamidite was treated with 1M HCl solution following the procedure described for Example 25 to yield the corresponding phosphorochloridite. 31P NMR (toluene): 165 ppm. The phosphochloridite was then reacted with di(2-tolyl)-2,2'-dihydroxy-1,1'-binaphthalene-3,3'-dicarboxylate in the same manner as described for Example 19. 31P NMR (toluene): 125 (major), 127 (minor), 142 (minor). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; for 20h; | A solution of <strong>[141483-15-0]2-fluoro-5-trifluoromethylphenol</strong> (25 g) in reagent grade acetone (0.55 L) is treated with solid potassium carbonate (7.7 g) followed by the rapid addition of neat bromoacetonitrile (10 mL). The heterogenous mixture is stirred vigorously for approximately 20 hours whereupon it is poured into water and extracted into diethyl ether. The combined ether extracts are washed with saturated sodium chloride and dried over anhydrous potassium carbonate. Filtration and concen-tration under reduced pressure gives a pale orange solid which is then chromatographed on silica gel, eluting with dichloromethane, to give the desired product as white solid (28.3 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Add 4-bromophenol (5.0 g, 28.9 mmol) and potassium carbonate (12.0 g, 86.3 mmol) in acetone (100 mL) and stir for 10 minutes. Next, add bromoacetonitrile (2.4 mL, 34.7 mmol) and stir the reaction at room temperature. After 12 hours, concentrate the reaction and pour into water. Extract with ethyl acetate (3x100 mL). Wash with water (1x150 mL), and brine (1x150 mL), dry over magnesium sulfate, filter and concentrate under reduced pressure to provide crude product Purify the residue by flash chromatography (silica gel), eluting with 20% ethyl acetate: hexanes (isocratic) to provide 6 g (98%) of the desired product that is used in step B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; | Microwave experiments were carried out using a Personal Chemistry Smith Synthesizer, which uses a single-mode resonator and dynamic field tuning, both of which give reproducibility and control. Temperatures from 40-250C can be achieved, and pressures of up to 20bar can be reached. Intermediate 1: 5-Chloro-2-cyanomethoxybenzonitrile A solution of <strong>[13589-72-5]4-chloro-2-cyanophenol</strong> (2.5g) in acetone was treated with potassium carbonate (2.3g), followed by bromoacetonitrile (1.2mL) and the resulting mixture was stirred at room temperature overnight. The mixture was filtered and the filtrate was evaporated to dryness to give 5-chloro-2-cyanomethoxybenzonitrile (3.3g) as a pale yellow solid. 1H NMR (DMSO-d6): delta 5.40 (s, 2H), 7.45 (d, 1H), 7.85 (dd, 1H), 8.05 (d, 1H). | |
With potassium carbonate; In acetone; at 20℃; | Intermediate A: 5-Chloro-2-cyanomethoxybenzonitrile [Show Image] A solution of <strong>[13589-72-5]4-chloro-2-cyanophenol</strong> (2.5g) in acetone is treated with potassium carbonate (2.3g), followed by bromoacetonitrile (1.2mL) and the resulting mixture is stirred at room temperature overnight. The mixture is filtered and the filtrate is evaporated to dryness to give 5-chloro-2-cyanomethoxybenzonitrile (3.3g) as a pale yellow solid. 1H NMR (DMSO-d6): delta 5.40 (s, 2H), 7.45 (d, 1H), 7.85 (dd, 1H), 8.05 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With potassium hydroxide; In N,N-dimethyl-formamide; at 0 - 20℃; | KOH (1.7 g, 30.6 mmol) was added to a solution of Intermediate 37 (3.46 g, 15.3 mmol) in 35 mL of DMF at 0 C. Then BrCH2CN (3.2 mL, 45.9 mmol) was added dropwise. The mixture was stirred at r.t. o.n. Then 400 mL of ice-water was added and extracted with EtOAc. The organic phase was washed with brine, dried and evaporated. Purification by silica gel column (petroleum ether/EtOAc=1/3) gave 2.1 g of Intermediate 38 (yield 52%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.1% | With potassium carbonate; In acetonitrile; at 80℃; for 3h; | To a mixture of 4-bromophenol (2.00 g, 11.6 mmol, 1.00 eq) and 2-bromoacetonitrile (1.66 g, 13.9 mmol, 924 uL, 1.20 eq) in MeCN (30.0 mL) was added K2CO3 (3.99 g, 28.9 mmol, 2.50 eq), and the mixture was stirred at 80 C. for 3 hours. After completion, solids were removed by filtration and the filtrate concentrated. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=I/O to 10:1) to give 2-(4-bromophenoxy)acetonitrile (2.10 g, 9.83 mmol, 85.1% yield, 99.3% purity) as white solid. (0532) 1H NMR (400 MHz, Chloroform-d) δ 7.49 (d, J=9.2 Hz, 2H), 6.90 (d, J=9.2 Hz, 2H), 4.77 (s, 2H). |
With caesium carbonate; In ethyl acetate; acetonitrile; | Step 1: [(4-Bromophenyl)oxy]acetonitrile A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3 (7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80 C., under N2 overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.75 (s, 2H), 6.88 (m, 2H), 7.46 (m, 2H). | |
With caesium carbonate; In ethyl acetate; acetonitrile; | Step 1: [(4-Bromophenyl)oxy]acetonitrile A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3 (7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80 C., under N2 overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.75 (s, 2H), 6.88 (m, 2H), 7.46 (m, 2H). |
With sodium tris(acetoxy)borohydride; caesium carbonate; In acetonitrile; at 80℃;Inert atmosphere; | A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3(7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80 C., under N2overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. | |
2.40 g | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; | Bromoacetonitrile (1 .2 mL, 17.3 mmol) was added to a stirred suspension of 4-bromophenol (2.00 g, 1 1 .6 mmol) and potassium carbonate in DMF (60 mL). Once addition was complete, the resulting mixture was heated at 50C overnight. The reaction mixture was cooled to RT, diluted with EtOAc (150 mL) and the organic layer was separated, washed with water (2 x 70 mL), brine (2 x 40 mL) then dried by passing through phase separator. The organics were concentrated in vacuo and the crude compound was purified by silica gel chromatography eluting with 0-50% EtOAc//'so- hexane to afford 2-(4-bromophenoxy)acetonitrile (2.40 g). A portion of this material (1 .00 g, 4.72 mmol) was dissolved in dry THF (20 mL) under N2 and methylmagnesium bromide (3 M in Et20, 5.5 mL, 16.5 mmol) was added dropwise. The reaction mixture was heated to 60C for 1 h, then titanium (IV) isopropoxide (1 .4 mL, 4.72 mmol) was added dropwise. The reaction mixture was stirred at 50C for 16 h. The reaction mixture was partitioned between DCM and brine. The mixture was filtered through celite and the filter cake washed with DCM. The organic fraction was separated, washed with brine again, followed by washing with aq 10% NaOH (2x) to remove the phenol starting material, dried by passing through a phase separator and evaporated to dryness to afford the desired product A43 as a brown oil (712 mg, 62%); LC-MS. Rt 1 .48 min, (0515) AnalpH2_MeCN_4min(1); (ESI+) m/z 244.0, 246.0 (M+H)+. |
2.4 g | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; | bromoacetonitrile (1.2 ml_, 17.3 mmol) was added to a stirred suspension of 4-bromophenol (2.00 g, 1 1.6 mmol) and potassium carbonate (4.80 g,34.8 mmol) in DMF (60 ml_). Once addition was complete, the resulting mixture was heated at 50C overnight. The reaction mixture was cooled to RT, diluted with EtOAc (150 ml_) and the organic layer was separated, washed with water (2 x 70 ml_), brine (2 x 40 ml_) then dried by passing through a phase separator. The organics were concentrated in vacuo and the crude compound was purified by silica gel chromatography eluting with 0-50% EtOAc//so-hexane to afford 2-(4-bromophenoxy)acetonitrile (A28) (2.40 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Bromoacetonitrile (0.208 mL, 3.12 mmol) was added to a slurry of (lS,4S)-2-oxa- 5-azabicyclo[2.2.1]heptane hydrochloride (0.353 g, 2.60 mmol) , DMSO (13 mL) and MP-carbonate (3.17 mmol/g, 2.5X, 6.5 mmol, 2.05 g). After shaking overnight, 0.52 mmol trisamine (4.17 mmol/g, 125 mg) was added, and the slurry was shaken for an additional 2 h. The slurry was filtered and the resulting 2-((lS,4S)-2-oxa-5- azabicyclo[2.2.1]heptan-5-yl)acetonitrile/DMSO solution was used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With potassium carbonate; sodium iodide; In acetonitrile; at 70℃; | A mixture of 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)- lH- pyrazole (0.50 g, 2.58 mmol), sodium iodide (39 mg, 0.26 mmol) bromoacetonitrile (1 .3 g, 10.8 mmol) and potassium carbonate (1.0 g, 7.8 mmol) in acetonitrile (10 mL) was heated at 70 C overnight. Water was added and the solution was extracted with EtOAc (3x). The organic was dried over Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography ( 10% to 100% EtOAc/hexane) to obtain 2-(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)-lH-pyrazol-l-yl)acetonitrile (0.38g, 63% yield). MS (ESI) m/z: 234.1 (M+H+). |
39% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 24h; | A solution of 4-(4,4, 5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H- pyrazole (5.11 g, 26.3 mmol) in DMF (50 mL) was treated with bromoacetonitrile (2.20 mL, 31.6 mmol) and K2CO3() (5.46 g, 39.5 mmol). The resulting suspension was stirred for 24 h at 100 C. The reaction mixture was cooled to ambient temperature, diluted with water (100 mL) then extracted with EtOAc (3 x 250 mL). The combined organic extracts were washed with water (3 x 50 mL) and brine (50 mL) then dried over anhydrous Na2SO4(). Following filtration, the organic extracts were concentrated under vacuum then purified by silica chromatography (10-60% Hexanes/EtOAc as the gradient eluent) to afford the title compound (2.42 g, 39% yield). ?H NIVIR (400 MHz, DMSO-d6) 8.04 (s, 1H), 7.71 (s, 1H), 5.49 (s, 2H), 1.25 (s, 12H). |
With potassium carbonate; sodium iodide; In acetonitrile; at 70℃; for 24h; | [00769] Compound 48 was prepared in 2 steps according to the following procedures: 4-(4,4,5,5- tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrazole (2.61 mmol, 1.0 equiv), bromoacetonitrile (4.2 equiv), sodium iodide (0.1 equiv) and potassium carbonate (3.0 equiv) were suspended in acetonitrile (10 mL) and heated to 70 C for 24h after which the reaction was cooled, partioned between water and brine and extracted with ethyl acetate. The combined organics were concentrated onto silica gel (4g) and purified using flash silica gel chromatography (Silicycle Si-40g, gradient 10-100% ethyl acetate/hexanes) to provide pinacol ester 47.47 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 20.0℃; for 1.5h; | 4-(3-(2H-1,2,3-Triazol-2-yl)phenylamino)-2-((1R,2S)-2-aminocyclohexylamino)pyrim carboxamide was prepared by the same scheme shown in Example 1 for 4-(3-(2H-1,2,3-triazol- 2-yl)phenylamino)-2-((1S,2R)-2-aminocyclohexylamino)pyrimidine-5-carboxamide. 4-(3-(2H-1,2,3-Triazol-2-yl)phenylamino)-2-((1R,2S)-2-aminocyclohexylamino)pyrimidine-5-carboxamide (80 mg, 0.2 mmol) was dissolved in 3 mL NMP. To it were added DIEA (70 mu, 0.4 mmol) and bromoacetonitxile (26 muEpsilon, 0.4 mmol). The mixture was stirred at RT for 1.5 h and diluted with a methylamine/methanol solution. The mixture was concentrated in vacuo, acidified with TFA and subjected to reverse phase preparative HPLC to isolate the title compound. MS found for C21H24N10O as (M+H)+ 433.3. UV: lambda=249 nm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.54% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; | Step 2: 2-(4-(Methylthio)-1 H-pyrazol-1-yl)acetonitrile Sodium hydride (631 mg, 16 mmol) was added to a solution of 4-(methylthio)-1 H- pyrazole (1500 mg, 13.14 mmol) in anhydrous tetrahydrofuran (30 mL) under nitrogen at 0C. The reaction mixture was stirred at 0C until gas evolution was no longer observed. Bromoacetonitrile (1.005 mL, 14.43 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 18 h. The mixture was poured into a solution of aqueous ammonium chloride (30 mL) and was extracted with ethyl acetate (60 mL x 3). The combined organics were dried over sodium sulfate. The residue was filtered through a plug of silica gel which was eluted with ethyl acetate and the filtrate was concentrated under reduced pressure. The crude material was purified via flash chromatography (0-50% ethyl acetate in heptanes) to afford 2-(4-(methylthio)-1 H- pyrazol-1-yl)acetonitrile (1460 mg, 72.54 %). MS (ES+) (M+H) 154.1 ; LCMS retention time 0.40 min (Method N). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | General procedure for synthesis of 2-(2-substituted-lH-indol-l-yl)acetonitriles (2) from indoles (1): A solution of 2-(trifluoromethyl)-lH-indole (1 lb) (0.5 g, 2.7 mmol) in DMF (2.5 mL) was added to a suspension of NaH (160 mg, 1.5eq) in DMF (3 mL) at 0 oC, and the resulting reaction mixture was stirred for 30 minutes. Then bromoacetonitrile (0.27 mL, 1.5eq) in DMF (2.5 mL) was introduced into the above reaction at 0 C, and then the reaction was brought to room temperature overnight. Water (20 mL) was added to quench the reaction, then the product was extracted with ethyl ether (30 mL x 3). Organics were washed with water, brine and dried over Na2S04 and concentrated. The crude mass on silica gel chromatography, eluting with 0- 10% ethyl acetate furnished (12b) (865 mg, 71 ) yield; 85%) based on recovered starting material). 2-(2-Trifluoromethyl-lH-indol-l-yl)acetonitrile (12b). 1H NMR (CDC13): delta 7.70 (d, J = 8 Hz, 1H), 7.44 (m, 2H), 7.28 (t x d, J = 7.2, 1.6 Hz, 1H), 7.04 (s, 1H), 5.1 (s, 2H). LCMS (ESI): > 95% purity at lambda 254, MS; m/z, 225 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | A solution of <strong>[51746-85-1]3-(1H-imidazol-4-yl)pyridine</strong> (8.0 g, 55.0 mmol) in tetrahydrofuran (100 mL) was added to a stirred and cooled (0 C.) suspension of NaH (60% dispersion in mineral oil, 3.0 g, 75.0 mmol) in THF (50 mL). Stirring continued for 30 min, and 2-bromoacetonitrile (6.5 g, 55.0 mmol) was added. After addition, the reaction mixture was stirred for 1 h at room temperature and then concentrated by evaporation. The residue was purified by silica gel chromatography (DCM/MeOH=10:1) to give the tile compound (7.5 g, 80% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate; In acetonitrile; at 50℃; for 5h; | To a solution of <strong>[5847-59-6]2-bromo-4-nitrophenol</strong> (40.7 g, 187 mmol), bromoacetonitrile (14.30mL, 205 mmol) in acetonitrile (600 mL) was added potassium carbonate (31.0 g, 224mmol) and the resulting mixture was heated to 50 C for 5 h. The reaction mixture wasconcentrated, dissolved in EtOAc (30 mL) and washed with H20 (30 mL), iN NaOH, and brine. The organic layer was concentrated and the residue was purified by column chromatography (silica gel, 2:8 ethyl acetate: petroleum ether) to obtain the title compound.Yield: 44.02 g (92 %); 1H NMR (300 MHz, DMSO-d6): O 4.98 (5, 2H, CH2), 7.13 (d, 1H,= 9.3 Hz, Ar), 8.29 (dd, 1 H, J1 = 9.3 Hz, J2 = 2.4 Hz, Ar), 8.54 (d, 1 H, J = 2.4 Hz, Ar); MS (El, 70 eV): mlz 252.1 (M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.37% | With potassium carbonate; In acetonitrile; at 60℃; for 2h; | To a mixture of bromoacetonitrile (2.94 mL, 42.18 mmol), <strong>[4983-28-2]2-chloropyrimidin-5-ol</strong>(5 g, 38.30 mmol) in CH3CN (100 mL) is added potassium carbonate (7.94 g, 57.45mmol). The reaction mixture is heated to 60 °C for 2 hours. After cooling to roomtemperature, the solid is filtered and the filtrate is concentrated under reduced pressure.The residue is purified by silica gel flash chromatography eluting with a gradient of 100percentether to 1/1 ether/ethyl acetate to give the title compound (6 g, 35.38 mmol, 92.37percent) as awhite solid. Mass spectrum (mlz): 170 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 19h; | Synthesis of In the N.N-dimethylformamide (3.7 mL) solution of 6-chloro indoline (170 mg, 1.1mmol), bromoacetonitrile (0.12 mL, 1.7mmol) and potassium carbonate (230 mg, 1.7mmol) was added at room temperature followed by stirring for 19 hours at 70 C..The reaction mixture was added water (30 mL) at room temperature, followed by extraction with ethyl acetate (30 mL). The organic layer was dried over sodium sulfate, and concentrated. The resulting concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane = 25/75) with purified childAnd afforded the 2- (<strong>[52537-00-5]6-chloro-indoline</strong>-1-yl) acetonitrile as a white solid (210 mg, 97% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 50℃; for 0.5h; | <strong>[2105-96-6]4-<strong>[2105-96-6]fluoro-3-nitrophenol</strong></strong> (933 mg, 5.94 mmol) was dissolved in DMF (11.900 ml) and cesium carbonate (2709 mg, 8.31 mmol) was added at room temperature. Then, 2- bromoacetonitrile (0.496 ml, 7.13 mmol) was added and the reaction stirred at 50 °C. After 30 minutes, the reaction was diluted with water and extracted with EtOAc three times. The organics were combined and washed with half-saturaed aq. NaCl solution, dried with sodium sulfate, filtered, and concentrated in vacuo to give 96A (deep, red oil, 1.12 g, 5.42 mmol, 91 percent yield). MR (400 MHz, chloroform-d) delta: 7.67 (dd, J=6.1, 2.8 Hz, 1H), 7.27-7.36 (m, 2H), 4.84 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; for 1.5h; | 3.130. Compound 118: (lR,2R)-N-[6-[5-(cyanomethoxy)-2-ethyl-N-methyl-anilino]-l-methyl- imidazo[4,5-c]pyridin-4-yl]-2-fluoro-cyclopropanecarboxamide 3.130.1. Step i): 2-(4-bromo-3-nitro-phenoxy)acetonitrile Bromoacetonitrile (11.5 mmol) is added to a mixture of <strong>[78137-76-5]4-bromo-3-nitrophenol</strong> (9.22 mmol) and K2CO3 in CH3CN (15 mL). The mixture is stirred for 1.5 h. The mixture is concentrated and the residue is partitioned between DCM and sat. NaHCC>3. The two phases are separated and the organic layer is dried (filtered through phase separator) and concentrated to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.6% | The (26.4g, 1.1mol) magnesium chips and 0.1g iodine placed in 2L three-necked flask,And add 60ml of tetrahydrofuran Stir the 1-bromo-7-methoxynaphthalene (237.1g, 1.0mol) was added to 360ml of tetrahydrofuran in a dropping funnel to make a mixed solution, a few drops slowly to the reaction flask with stirring After 5 min, the solution in the reaction flask was slightly boiled and cooled in an ice-water bath to 5 C. 360 ml of tetrahydrofuran was added to the reaction flask, and the mixture prepared above was added dropwise under stirring to control the reaction temperature at 38 C.,The reaction time 2h to give 1-bromo-7-methoxy-naphthalene testThe reaction solution.(132.0 g, 1.1 mol) of bromoacetonitrile was added to 360 ml of tetrahydrofuran to prepare a mixture of bromoacetonitrile and the resultingThe reaction solution of 1-bromo-7-methoxy-Naphthalene reagent was cooled to 0 C in a reaction flask. The prepared mixed solution of bromoacetonitrile was slowly added dropwise to the reaction flask with stirring. After the dropwise addition, the temperature was raised to 55 C The reaction was carried out for 2h to obtain a reaction solution of (7-methoxy-1-naphthyl) acetonitrile. The reaction solution of the obtained (7-methoxy-1-naphthyl) acetonitrile was cooled to 25 C and added with a mass fraction of 10% Salt water to terminate the reaction, and then separated, dried and concentrated to 360ml of tetrahydrofuran, and then cooled crystallization, after filtration, 50 C blast drying186.7g(7-methoxy-1-naphthyl) acetonitrile, yield 94.6%, purity 99.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | At 10 C, Methyl 1-hydroxy-1-cyclopropanecarboxylate (50.00 g, 0.43 mol) was added to tetrahydrofuran (400 mL).Nitrogen protection, adding 60% sodium hydride (34.4 g, 0.86 mol) in batches at the same temperature.After the addition was completed at 10 C for 15 minutes, bromoacetonitrile (103.2 g, 0.86 mol) was further added, and the reaction was carried out at 10 C for 15 minutes. Then, water (100 mL) was slowly added dropwise at 0 C, and water (400 mL) was added.The aqueous phase was extracted with ethyl acetate (200 mL*2), and the organic phase was combined, and the organic phase was washed with saturated brine (100 mL).Concentrated organic phase,Sand column chromatography (petroleum ether: ethyl acetate = 4:1 to 3:1)Get 61.3g of light yellow liquid,That is, Intermediate 1, the yield was 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Toa solution of <strong>[1196473-37-6]benzo[c][1,2]oxaborole-1,6(3H)-diol</strong> (2 g, 13.34 mmol) inN,N-dimethylformamide (20 mL) was added NaH (1.60 g, 66.7 mmol) at 0 °C. After stirring for 1 h, 2-bromoacetonitrile(1.92 g, 16.01 mmol) was added. The mixture was stirred for 12 hours at roomtemperature. The mixture was dilutedwith water (20 mL), acidified to pH 3 with 1 N aqueous HCl solution, and extractedwith ethyl acetate (3 x 20 mL). Theorganic phase was washed with brine, dried over anhydrous Na2SO4,concentrated, and purified by silica gel chromatography using petroleum ether ?ethyl acetate (5:1) to give2-((1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)oxy)acetonitrile (1.7 g, 67percent yield) as a brown oil. LCMS: [M+H]+: 190.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 3h; | General procedure: To a stirred solution of 24b-f (1.0 mmol) in anhydrous EtOH was added 4-methylbenzenesulfonate, pyridin-1-ium (PPTS) (300.0 mg,1.2 mmol), and refluxed overnight. The mixture was concentrated to give crude 25b-j which was used for the next step directly withoutfurther purification. To a stirred solution of 25a (commercially available, 120.0 mg, 1.0 mmol) or 25b-j (1.0 mmol) in DMSO (5 mL)was added bromoacetonitrile (300.0 mg, 2.5 mmol), K2CO3 (556.8 mg, 4 mmol) at room temperature. The mixture was stirred for 3hours at room temperature, quenched by H2O (30 mL), and extracted by EtOAc (30 mL × 2). The organic layer was concentrated anddissolved in anhydrous THF (5 mL). LiAlH4 (1 M solution in THF, 1 mL) was added at room temperature and stirred for 1 hour. Themixture was quenched by ice and filtered over celite. The filtrate was washed by saturated Na2CO3 solution (10 mL). The aqueouslayer was extracted by EtOAc (15 mL × 3). The combined organic layer was concentrated to give the crude mixture 26a-j which wasused for the next step directly without further purification | |
With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 3h; | General procedure: To a stirred solution of 12a (commercially available, 236.1 mg,1.8 mmol) or 12b-f (1.8 mmol) in DMSO (5 mL) was added bromoacetonitrile(300.0 mg, 2.5 mmol), K2CO3 (556.8 mg, 4 mmol) atroom temperature. The mixture was stirred for 3 h at room temperature,quenched by H2O (30 mL), and extracted by EtOAc(30 mL 2). The organic layer was washed by saturated sodiumchloride solution, and dried over anhydrous MgSO4, filtered andconcentrated. The residue was purified by Flash column chromatography(DCM/MeOH, 0e10percent) to afford the crude target compounds13a-f (15-30percent yield for two steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Compound 1E (5 g, 23 mmol) was dissolved in anhydrous tetrahydrofuran (50 ml) and cooled to -78 C. Lithium hexamethyldisilazide (1.0M tetrahydrofuran solution) (25 ml, 25 mmol) was then added dropwise. The solution was stirred for 1 hour. Bromoacetonitrile (3 g, 25 mmol) was then added dropwise. Stir for 30 minutes. Then gradually warmed to room temperature.When TLC showed that the reaction was complete, it was quenched by the addition of a saturated aqueous ammonium chloride solution (200 ml), and then extracted with ethyl acetate (3 × 100 ml). The combined organic layers were washed with brine and dried over sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10: 1 to 3: 1 (volume ratio V: V)) to obtain the target compound 1F (4.8 g, yellow solid) in a yield of 82% . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With dihydrogen peroxide; sodium hydroxide; In water; N,N-dimethyl-formamide; at 80℃; for 4h;Green chemistry; | General procedure: All reactions were carried out under air conditions. A mixture of arylboronic acid (0.5 mmol), 2-bromoacetonitrile (0.7 mmol), base (0.8 mmol) and 3 mL DMF were taken in an oven dried 10 mL round bottomed flask. To this 30% aq.H2O2 0.08 mL was added dropwise and stirred at 80 0C for 4 h. After completion of the reaction (monitored by TLC) and cooling to ambient temperature, distilled H2O (10 mL) was added to the mixture, the aqueous layer was extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (Na2SO4 ) and concentrated, and the residue was purified by thin layer chromatography (petroleum ether/hexane/dichloromethane) to give the desired product. |
Tags: 590-17-0 synthesis path| 590-17-0 SDS| 590-17-0 COA| 590-17-0 purity| 590-17-0 application| 590-17-0 NMR| 590-17-0 COA| 590-17-0 structure
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