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CAS No. : | 31106-82-8 | MDL No. : | MFCD01863544 |
Formula : | C6H7Br2N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JQDNCGRNPYKRAO-UHFFFAOYSA-N |
M.W : | 252.93 | Pubchem ID : | 2734720 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.17 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 47.11 |
TPSA : | 12.89 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.09 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 2.47 |
Log Po/w (WLOGP) : | 2.78 |
Log Po/w (MLOGP) : | 1.8 |
Log Po/w (SILICOS-IT) : | 2.4 |
Consensus Log Po/w : | 1.89 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.39 |
Solubility : | 0.103 mg/ml ; 0.000406 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.39 |
Solubility : | 1.04 mg/ml ; 0.00412 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.28 |
Solubility : | 0.134 mg/ml ; 0.00053 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.68 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P501-P260-P264-P280-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P405 | 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 |
---|---|---|
87% | With potassium carbonate; In N,N-dimethyl-formamide; at 18 - 25℃; for 16h; | To a solution of ethyl 3- (trifluoromethyl) -lH-pyrazole-4- carboxylate (10.0 g, 48.00 mmol) in DMF were added 2-(bromomethyl) pyridine hydrobromide (13.4 g, 52.80 mmol) and potassium carbonate (13.3 g, 96.1 mmol). The mixture was stirred for 16 hours at room temperature and filtered. The solid was dried under vacuum to give ethyl 1- (pyridin-2- ylmethyl) -3- ( trifluoromethyl) -lH-pyrazole-4-carboxylate (12.5 g,87%) as crystals: 1H NMR (CDCl3) delta 1.34 (t, 3H, J = 7.0 Hz), 4.32 (q, 2H, J = 7.0 Hz), 5.45 (s, 2H), 7.22 (d, IH, J = 7.8 Hz), 7.29 (m, IH), 7.72 (m, IH), 8.16 (s, IH), 8.61 (m, IH).. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile; at 55℃; for 0.5h; | In a 100 mL round bottomed flask was placed 2-aminomethylpyridine (2.50 g, 0.023 moles). The system was placed under nitrogen. The solid was dissolved in 20 mL of acetonitrile followed by the addition of 7 mL of triethylamine. Next the 2-bromomethylpyridine hydrobromide (5.80 g, 0.023 moles) was added. The reaction mixture was allowed to stir for 0.5 hours at 55 C., whereupon the reaction was vacuumed down to residue. The mixture was purified using a large silica column (10% methanol/methylene chloride). 1H NMR (CDCl3, ppm): 3.98 (s, 4H), 7.15 (m, 2H), 7.55 (m, 2H), 7.65 (m, 2H), 8.55 (m, 2H). Mass Spectroscopy demonstrated the molecular weight to be 291 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; In acetonitrile; for 24h;Heating / reflux; | 131 6-("("3S.5RV3.5-Dimethyl-4-pyridin-2-ylmethyl-pirhoerazin-l-ylmethylV2-(lH- indazol-4-ylV4-mophiholin-4-yl-thienor3,2-dlpyrimidine.Via 2-Chloro-6-((3S,5R)-3,5-dimethyl-4-pyridin-2-ylmethyl-piperazin-l- ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared from (2S,6R)-2,6- dimethyl- l-pyridin-2-ylmethyl-piperazine. Amine preparation: (3R,5S)-3,5- dimethyl-piperazine-1-carboxylic acid tert-butyl ester (845mg), 2-(bromomethyl)- pyridine hydrobromide (Ig) and potassium carbonate (1.15g) was heated to reflux in MeCN (1OmL). After heating for 24 h the reaction mixture was diluted with DCM, washed with sodium bicarbonate solution, dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography to yield (3S,5R)-3,5- dimethyl-4-pyridin-2-ylmethyl-piperazine-l-carboxylic acid tert-butyl ester (867mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt. 1H NMR (400MHz, CDCl3) 1.00 (d, J=6.0Hz, 6H), 1.54 (s, 2H), 2.05 (m, 2H), 2.84 (m, 4H), 3.81 (s, 2H), 3.92 (m, 4H), 4.10 (m, 4H), 7.11 (m, IH), 7.38 (s, IH), 7.51 (m, IH), 7.61 (m, 3H), 8.29 (d, J=7.4Hz, IH), 8.51 (d, J=4.5Hz, IH), 9.03 (s, IH); MS (ESI+) 555 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.22 g (19.5%) | With potassium carbonate; In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide; | EXAMPLE 1 2-Methylnicotine or 2-Methyl-3-(1-methyl-2-pyrrolidinyl)pyridine An ethereal solution of 2-bromomethylpyridine, obtained by treating 9.0 g (35.6 mmol) of 2-bromomethylpyridine hydrobromide with aqueous sodium bicarbonate, was added to 4.30 g (39 mmol) of <strong>[20297-37-4]1-methyl-2-cyanopyrrolidine</strong> in 100 ml dimethylsulfoxide. The ether was removed at reduced pressure, and the solution was stirred at room temperature for 24 hrs. To the solution was added 500 ml dry tetrahydrofuran and, after cooling to -20, 4.0 g (35.8 mmol) of freshly sublimed potassium-t-butoxide was added. The reaction mixture was stirred for 5 hours at -20, after which the tetrahydrofuran was removed under reduced pressure. A mixture of 50 ml ether and 50 ml ice water was added and the organic phase was separated. The aqueous phase was further extracted, and the combined extracts washed with three 50 ml portions of saturated sodium chloride and 10 ml 50% potassium hydroxide, and then dried over sodium sulfate. Removal of the ether gave 3.74 g of a crude product which was dissolved in 60 ml ether and added to a slurry of 1.41 g (37 mol) of lithium aluminium hydride in 120 ml ether maintained at 0. The solution was stirred at 0 for 0.5 hour and then heated under reflux for 3 hours. After cooling to 0, 15 ml of saturated potassium carbonate was added dropwise, and the resulting mixture was heated under reflux for 0.5 hour. The mixture was filtered, and the filtrate was extracted with two 10 ml portions of 20% aqueous acetic acid. The aqueous phase was then adjusted to ~pH 10 with 50% aqueous potassium hydroxide, and the basic solution was extracted with four 25 ml portions of ether. The ether extracts were combined, washed with saturated sodium chloride, and dried over sodium sulfate. After filtration and removal of the ether, the crude product was distilled (56-59/0.1 mm) to give 1.22 g (19.5%) of 2-methylnicotine which was a colorless liquid. Anal. Calcd. for C11 H16 N2: C, 74.95; H, 9.15; N, 15.90 Found: C, 75.04; H, 9.06; N, 15.68 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 20℃; for 0.666667h; | To a solution of <strong>[90030-48-1]SMOPS</strong> (4.8 g, 0.028 mol) in DMSO (dry, 50 mL) was added 2- bromomethyl pyridine HBr (5 g, 0.019 mol) at r.t.. After 40 min pH of the solution was adjusted to 8 by the addition of aqueous bicarbonate solution. The reaction mixture was extracted with EtOAc (4 x 100 mL), the organic layers were combined, dried over anhydrous sodium sulphate, filtered and the solvents were removed in vacuo. The residue was redissolved in a mixture of solvents consisting of THF (200 mL) and methanol (10 mL) and treated with a solution of sodium methoxide (4 mL, 25%) over a period of 10 min. After stirring for 40 min, the reaction mixture was concentrated in vacuo and dissolved in water (20 mL). Followed by addition of a solution of hydroxylamine-O- sulfonic acid (12.66 g, 0.099 mol), sodium acetate (7g) in water (60 mL) followed by stirring at r.t.. After 48 h pH of the solution was adjusted to 9 by the addition of aqueous bicarbonate solution and the mixture subjected to freeze drying. The solid thus obtained was treated with methanol, methanolic layer separated and concentrated. The residue was purified by flash chromatography on silica using a gradient of EtOAc in pet ether followed by EtOAc and then with MeOH in EtOAc to give l-Pyridin-2-ylmethanesulfonamide. Yield: 400 mg (12 %). EPO <DP n="184"/>1H NMR (400 MHz, DMSO-d6) delta 4.42-4.45 (2H, m), 6.90-6.95 (2H, m), 7.33-7.39 (IH, m), 7.45-7.50(1H3 m), 7.78-7.85 (IH, m), 8.53-8.59 (IH, m) MS m/z: 173 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With N-ethyl-N,N-diisopropylamine; In methanol; dichloromethane; N,N-dimethyl-formamide; | Preparation of 1-pyridine-2-ylmethyl-1H-imidazole-2-carbaldehyde: To a solution of the 2-imidazolecarboxaldehyde (545 mg, 5.67 mmol) and 2-(bromomethyl)pyridine hydrobromide (1.58 g, 6.24 mmol) in DMF (20 mL) was added N,N-diisopropylethylamine (3.0 mL, 17.01 mmol). The reaction mixture was heated to 80 C. overnight. Then it was cooled and quenched with saturated NaHCO3 (20 mL). It was extracted with CH2Cl2 (c*20 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered, concentrated, and dried in vacuo to afford a dark brown oil. Purification by flash column chromatography on silica gel using 1%?2% CH3OH/CH2Cl2 afforded the product as a yellow solid (397 mg, 37%). 1H NMR (CDCl3) delta 5.71 (s, 2H), 7.18-7.24 (m, 2H), 7.32 (s, 1H), 7.36 (s, 1H), 7.65 (td, 1H, J=10.4, 1.5 Hz), 8.56 (d, 1H, J=4.5 Hz), 9.82 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium hydride; In N,N-dimethyl-formamide; at -40 - 20℃; | Solid <strong>[4692-99-3]6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione</strong> (35.83 g, 202 mmol) was added to a suspension of NaH (60% in Min. oil, 18.2 g, 455 mmol) in dry DMF (350 mL) stirred at -40 C. under argon. The solution was allowed to come to room temperature by removing the dry ice bath. After stirring at room temperature briefly, the solution was again cooled to -20 C. Then 2-bromomethylpyridine hydrobromide (55 g, 217 mmol) was added to the solution. The solution was allowed to come to room temperature and stirred overnight at the same temperature under argon. The solution was poured into ice cold 5% aqueous NaCl solution (5 L). The solids formed were filtered and air dried at room temperature over night. The dry solids were suspended in hexanes (1250 mL) and stirred vigorously at room temperature for 1 h. The solids were filtered and dried under vacuum. Yield 45 g (83%). 1H-NMR (DMSO-d6): delta 2.33 (s, 3H), 5.34 (s, 2H), 7.17 (d, J=8.8 Hz, 1H), 7.30 (m, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.55 (dd, J=2.0, 8.8 Hz, 1H), 7.78 (m, 1H), 7.85 (d, J=1.6 Hz, 1H), 8.50 (d, J=4.4 Hz, 1H); EIMS m/z 269 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of <strong>[321-69-7]6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione</strong> (3.72 g, 20.55 mmol) was added to a suspension of NaH (60% in Min. oil, 1.80 g, 45.21 mmol) in dry DMF (30 mL) stirred at room temperature under argon. The solution was further stirred at room temperature for 30 min. Solid 2-bromomethylpyridine hydrobromide (5.71 g, 22.60 mmol) was added to the solution. The solution was further stirred at room temperature for 3 h and quenched with few drops of water. Excess DMF was evaporated under vacuum. The residue was suspended in water and extracted by CH2Cl2. The combined organic phase was dried over MgSO4 and concentrated to a residue. The crude product was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 32h; | 152.ii (ii) 1 ,1-Dimethylethyl (3,5-dimethyl-1 H-pyrazol-4-yl)acetate (0.100 g, 0.478 mmol) was dissolved in dimethylformamide (5 ml) and treated with cesium carbonate (0.341 g, 1.05 mmol) and 2-(bromomethyl)pyridine hydrobromide (0.133 g, 0.526 mmol). The mixture was stirred at room temperature for 27 hrs and then treated with a further quantity of cesium carbonate (0.170 g, 0.526 mmol). Stirring was continued for a further 6 hrs at room temperature and then the mixture was evaporated in vacuo. The resulting residue was partitioned between ethyl acetate (40 ml) and water (30 ml). The aqueous layer was separated and extracted with ethyl acetate (2 x 30 ml) and then the combined organic layers were dried and the solvent evaporated to give a yellow gum. The gum was loaded onto a 10g silica SPE cartridge in a minimum of dichloromethane and then eluted with a 50-90% mixture of ethyl acetate in petroleum ether (40/60). The product-containing fractions were combined and evaporated to give partially purified 1 ,1-dimethylethyl [3,5-dimethyl-1- (2-pyridinylmethyl)-1 H-pyrazol-4-yl]acetate as a yellow gum (0.070 g). This was used in the next step without further purification, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate; In acetonitrile; at 18 - 25℃; | In a 200 mL round-bottomed flask was added <strong>[66171-50-4]methyl 6-hydroxynicotinate</strong> (1.211 g, 7.91 mmol), 2-(bromomethyl)pyridine hydrobromide (2.0 g, 7.91 mmol), and K2CO3 (4.37 g, 31.63 mmol) in MeCN (30 mL) to give a white suspension. The reaction was stirred at RT overnight. The solvent was removed under reduced pressure, and to the residue was added water (20 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (2 X 10 mL) and the combined organic phases were concentrated to give the crude product, which was purified by ISCO MPLC (30-100% EtOAc/hexane) to give the title compound (Yl.8 g, 95% yield). 1H NMR (DMSO-d6) delta 3.80 (s, 3 H), 5.30 (s, 2 H), 6.44 (d, 1 H), 7.29 (dd, 1 H), 7.34 (d, 1 H), 7.78 (td, 1 H), 7.84 (dd, 1 H), 8.48 (d, 1 H), 8.66 (d, 1 H). MS (M+H+) = 245. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 80℃; for 2h; | In a 200 mL round-bottomed flask was added <strong>[30766-12-2]methyl 5-hydroxypicolinate</strong> (2.092 g, 13.66 mmol), 2-(bromomethyl)pyridine hydrobromide (3.46 g, 13.66 mmol), and K2CO3 (1.888 g, 13.66 mmol) in MeCN (110 mL) to give a suspension. The reaction was heated to 80 0C for 2h. After Concentration under reduced pressure, the residue was diluted with water (20 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (2 X 30 mL), and the combined organic layers were dried (Na2SO4) to give the crude product that was purified by ISCO MPLC (10% MeOH/DCM) to give the title compound. 1U NMR (DMSO-d6) 53.85 (s, 3 H), 5.36 (s, 2 H), 7.38 (dd, 1 H), 7.60 (m, 2 H), 7.87 (td, 1 H), 8.05 (d, 1 H), 8.49 (d, 1 H), 8.60 (d, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium carbonate In ethanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With potassium carbonate; In acetone; for 72h;Reflux; Inert atmosphere; | 6-(2-Picolinyloxy)-2-cyanobenzothiazole: (Bromomethyl)pyridine hydrobromide (1.87 g, 7.38 mmol) and <strong>[939-69-5]2-cyano-6-hydroxybenzothiazole</strong> (1.00 g, 5.68 mmol) were suspended in acetone (50 mL). After introduction of potassium carbonate (1.96 g, 14.2 mmol), the suspension was refluxed for 72 h under nitrogen. After cooling down the mixture and filtering the solids, the filtrate was concentrated and the residue was purified by silica gel chromatography using 50percent-75percent ethyl acetate in heptane. A yellowish solid was obtained in 72percent yield. MS (ESI+): m/z 267.90 (M+H)+; calc'd: 268.05 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; | 1.2 Preparation of N-4-chloro-3,5-bis(trifluoromethyl)phenyl)-N-(2-pyridinylmethyl)-2-pyridine methanamine (compound No. 27) (2) 120 mg of 4-chloro-3,5-bis(trifluoromethyl)aniline was dissolved in 2 mL of N,N-dimethylformamide, and 240 mg of 2-bromomethylpyridine hydrogenbromide and then 80 mg of sodium hydride were added and reacted at room temperature for about one hour. To the reaction solution, water was added and stirred, and then, it was extracted with ethyl acetate. Then, the crude product thereby obtained was purified by silica gel column chromatography (eluent: ethyl acetate) to obtain 120 mg of the desired product (melting point: 61°C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In N,N-dimethyl-formamide; mineral oil | 34.A A. A. Synthesis of 4-bromo-1-(pyridin-2-ylmethyl)-1H-indole-2,3-dione To a solution of 4-bromoisatin (8.94 g, 39.5 mmol) in anhydrous N,N-dimethylformamide (100 mL) was added sodium hydride (3.34 g, 86.9 mmol, 60% dispersion in mineral oil) in portions at 0° C. The brown reaction mixture was stirred for 30 min followed by the addition of a solution of 2-(bromomethyl)pyridine hydrobromide (10.0 g, 39.5 mmol) neutralized with sodium hydride (1.52 g, 39.5 mmol, 60% dispersion in mineral oil) in N,N-dimethylformamide at 0° C. The reaction mixture was stirred for 16 h and quenched with water (100 mL). The reaction mixture was extracted with diethyl ether (3*100 mL) and the aqueous layer was extracted with ethyl acetate (3*100 mL). The combined organic layers was washed with water (5*200 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with ether to afford the title compound (10.6 g, 85%) as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 8.53 (d, 1H), 7.67 (t, 1H), 7.30 (t, 2H), 7.25-7.19 (m, 2H), 6.94 (d, 1H), 5.04 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ 180.5, 157.3, 154.2, 152.3, 149.5, 138.4, 137.5, 128.6, 123.3, 122.3, 121.5, 116.4, 110.3, 45.8. |
85% | Stage #1: 4-bromoisatin With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-(bromomethyl)pyridine hydrobromide With sodium hydride In N,N-dimethyl-formamide at 0℃; for 16h; | 34.A To a solution of 4-bromoisatin (8.94 g, 39.5 mmol) in anhydrous N1N- dimethylformamide (100 mL) was added sodium hydride (3.34 g, 86.9 mmol, 60% dispersion in mineral oil) in portions at 0 0C. The brown reaction mixture was stirred for 30 min followed by the addition of a solution of 2-(bromomethyl)pyridine hydrobromide (10.0 g, 39.5 mmol) neutralized with sodium hydride (1.52 g, 39.5 mmol, 60% dispersion in mineral oil) in Λ/,Λ/-dimethylformamide at 0 0C. The reaction mixture was stirred for 16 h and quenched with water (100 mL). The reaction mixture was extracted with diethyl ether (3 x 100 mL) and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers was washed with water (5 x 200 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with ether to afford the title compound (10.6 g, 85%) as a brown solid: 1H NMR (300 MHz, DMSOd6) δ 8.53 (d, 1H), 7.67 (t, 1 H), 7.30 (t, 2H), 7.25-7.19 (m, 2H), 6.94 (d, 1 H), 5.04 (s, 2H); 13C NMR (75 MHz, DMSO-c/6) δ 180.5, 157.3, 154.2, 152.3, 149.5, 138.4, 137.5, 128.6, 123.3, 122.3, 121.5, 116.4, 110.3, 45.8. |
85% | Stage #1: 4-bromoisatin With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-(bromomethyl)pyridine hydrobromide In N,N-dimethyl-formamide at 0℃; for 16h; | 60 To a solution of 4-bromoisatin (8.94 g, 39.5 mmol) in anhydrous N, N- dimethylformamide (100 ml_) was added sodium hydride (3.34 g, 86.9 mmol, 60% dispersion in mineral oil) in portions at 0 0C. The brown reaction mixture was stirred for 30 min followed by the addition of a solution of 2-(bromomethyl)pyridine hydrobromide (10.0 g, 39.5 mmol) neutralized with sodium hydride (1.52 g, 39.5 mmol, 60% dispersion in mineral oil) in Λ/,Λ/-dimethylformamide at 0 0C. The reaction mixture was stirred for 16 h and quenched with water (100 ml_). The reaction mixture was extracted with diethyl ether (3 x 100 mL) and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers was washed with water (5 x 200 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with ether to afford the title compound (10.6 g,85%) as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 8.53 (d, 1 H), 7.67 (t, 1 H), 7.30 (t, 2H), 7.25-7.19 (m, 2H), 6.94 (d, 1H), 5.04 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ 180.5, 157.3, 154.2, 152.3, 149.5, 138.4, 137.5, 128.6, 123.3, 122.3, 121.5, 116.4, 110.3, 45.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With triethylamine In toluene Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Methyl 2,6-dioxo-l,2,3,6-tetrahydropyrimidine-4-carboxylate (5 g, 29.4 mmol) and DMF (118 mL) were combined and the resultant mixture was cooled with an ice bath. Lithium hydride (0.369 g, 44.1 mmol) was added in portions. The mixture was stirred for 20 minutes and ((chloromethoxy)methyl)benzene (5.00 mL, 32.3 mmol) was added via syringe. The mixture was stirred a 00C for 30 minutes. Lithium hydride (0.492 g, 58.8 mmol) was then added in portions and stirred for 10 minutes. 2-(Bromomethyl)pyridine hydrobromide (8.92 g, 35.3 mmol) was added in portions and stirred at 00C over 1 hour. The bath was removed and then stirred at room temperature for 2 hours. Water (25 mL) and methanol (25 mL) were added and the solvents were evaporated under vacuum at 65°C to leave a red oily solid, which was partitioned between IN NaOH (100 mL) and diethyl ether (50 mL). The organic layer was separated. The aqueous layer was washed with diethyl ether (2 x 50 mL) and the aqueous layer was acidified to pH=4 with 3N HCl. The aqueous layer was washed with diethyl ether (2 x 50 mL). The aqueous layer was then extracted with n-BuOH (4 x 100 mL). The organic layers from the n-BuOH extraction were combined and the solvent was evaporated under vacuum to give a solid, which was triturated with acetone and cooled in an ice bath. The resulting solid was isolated by filtration and dried under vacuum to give 4.86 g of a first crop of the title compound; a second and third crop were isolated to give a total of 5.53g of the title compound. MS [M+H] found 368. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; | Methyl 5-fluoro-2-(pyridin-2-ylmethoxy)benzoate (18a)A suspension of <strong>[391-92-4]methyl 5-fluorosalicylate</strong> (17) (2.50g, 13.2mmol), 2-(bromomethyl)pyridine hydrobromide (4.3g, 17mmol) and K2CO3 (6.3g, 45.3mmol) in DMF (125ml) was heated at90°C overnight. The reaction solvent was removed under vacuum and the residue partitioned between DCM and water. The oragenics were separated, dried and reduced onto silica.Purification by column chromatography (S1O2, DCM:MeOH 1 :0-->19: 1 over 30 min) gave the title compound (3.33g, 12.8mmol).NMR (CDCI3) delta 8.60 (1H, m), 7.79 (2H, m), 7.60 (1H, dd, J 8.8, 3.2), 7.15-7.28 (2H, m), 7.02 (1H, dd, J9.2, 4.1), 5.29 (2H, s), 3.96 (3H, s);MS (m/e) 262 [M+H]+, Rt 1.91min (QC Method 2) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With potassium carbonate In acetonitrile at 80℃; for 24h; | 2-(5-methoxy-2-methyl-l-(pyridin-2-ylmethyl)-lH-indol-3-yl)-N-(2-methoxypyridin- 4-yl)-2-oxoacetamide (77); [00302] To a solution of 5-methoxy-2-methyl- 1 H-indole ( 1.00 g, 6.20 mmol) in N,N- dimethylformamide (10 mL) at 0 °C was added sodium hydride (0.372 g, 9.31 mmol). The reaction was stirred at room temperature for 20 minutes, after which 2- (bromomethyl)pyridine hydrobromide (1.88 g, 7.44 mmol) was added. The reaction mixture was stirred at 80 °C for 24 hours, after which it was diluted with water, extracted with ethyl acetate (3 x 50 mL), washed with water, then washed with saturated sodium bicarbonate solution, dried (magnesium sulfate), filtered and concentrated. Purification was achieved by silica gel chromatography (ISCO 80 g) using 0 to 80% ethyl acetate in hexanes to afford 5- methoxy-2-methyl-l-(pyridin-2-ylmethyl)-l H-indole as a yellow-brown solid in 36% yield.[00303] 2-(5-methoxy-2-methyl- 1 -(pyridin-2-ylmethyl)- 1 H-indol-3 -yl)-N-(2- methoxypyridin-4-yl)-2-oxoacetamide was synthesized as a yellow solid in 8% yield starting from 5-methoxy-2-methyl-l-(pyridin-2-ylmethyl)-l H-indole using general procedure G. NMR (400 MHz, CDC13) δ (ppm): 9.33 (s, 1H), 8.58 (d, 1H), 8.12 (s, 1H), 7.70 (s, 1H), 7.57 (m, 1H), 7.31 (s, 1H), 7.19 (m, 2H), 7.14 (s, 1H), 6.86 (d, 1H), 6.71 (d, 1H), 5.41 (s, 2H), 3.96 (s, 3H), 3.81 (s, 3H), 2.65 (s, 3H). l-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)methyl)-5-methoxy-2-methyl-lH-indole (28); [00300] To a suspension of 5-methoxy-2 -methyl- 1 H-indole (0.280 g, 1.74 mmol) in acetonitrile (5 mL) was added 3-chloro-2-(chloromethyl)-5-(trifiuoromethyl)pyridine (0.400 g, 1.74 mmol) and potassium carbonate (0.481 g, 0.348 mmol) was heated to 70 °C for 18 hrs after which the reaction mixture was cooled to room temperature, diluted in water (30 mL), extracted with dichloromethane (3 x 20 mL), washed with saturated sodium chloride solution (1 x 50mL), dried (sodium sulfate), filtered and concentrated to a residue.Purification was achieved by silica gel chromatography using 0 to 40% ethyl acetate in hexanes to afford l-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)methyl)-5-methoxy-2-methyl- lH-indole (129 mg, 0.218 mmol, 13 % yield) as a solid.[00301] l-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)methyl)-5-methoxy-2-methyl-lH- indole was synthesized as a solid in 18% yield starting from l-((3-chloro-5- (trifluoromethyl)pyridin-2-yl)methyl)-5-methoxy-2-methyl- 1 H-indole using general procedure G. NMR (400 MHz, CDC13) δ (ppm): 9.07 (s, 1H), 8.58 (s, 1H), 8.15 (d, 1H), 7.99 (d, 1H), 7.79 (d, 1H), 7.29 (s, 1H), 7.17 (dd, 1H), 7.06 (d, 1H), 6.84 (dd, 1H), 5.60 (s, 2H), 3.99 (s, 3H), 3.86 (s, 3H), 2.74 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; potassium iodide; In ethanol; at 20℃; for 12h; | To a solution of (S)-diphenylprolinolsilyl ether 1 (326 mg, 1.0 mmol) in EtOH (15 mL) was added 2-bromomethyl pyridine hydrobromide (253 mg, 1.0 mmol), K2CO2 (276 mg, 2.0 mmol), and KI (17 mg, 0.1 mmol). The reaction mixture was stirred at room temperature for 12 h. The solution was filtered, the solvent was removed in vacuo and water (20 mL) was added to the residue. The aqueous solution was extracted with ethyl acetate (15 mL x 3). The combined organic phase was washed with brine and dried over Na2SO4. Filtration, removal of the solvent, and purification by falsh column chromatography (eluent: hexan/ethyl acetate = 3/1) afforded the product 2 (364 mg, 87%). [a]D20 = -58.4o (c = 1.75, CH2Cl2); 1H NMR (400 MHz, CDCl3) delta 8.67 (d, J = 4.4 Hz, 1H), 7.82 (dt, J = 9.6 and 1.6 Hz, 1H), 7.79-7.72 (m, 4H), 7.56-7.46 (m, 7H), 7.30 (dd, J = 6.4 and 5.2 Hz, 1H), 4.67 (d, J = 6.8 Hz, 1H), 4.18 (dd, J = 9.6 and 3.6 Hz, 1H), 3.92 (d, J = 10.8 Hz, 1H), 2.83-2.75 (m, 1H), 2.43 (dt, J = 15.6 and 6.0 Hz, 1H), 2.33-2.17 (m, 1H), 2.07-1.96 (m, 1H), 1.67-1.55 (m, 1H), 1.05-0.95 (m, 1H), 0.00 (s, 9H); 13C NMR (100 MHz, CDCl3) delta 161.5, 148.3, 144.3, 144.2, 136.1, 129.6, 127.2, 127.1, 126.8, 122.6, 121.3, 85.0, 71.7, 64.1, 55.0, 29.2, 23.8, 1.9; HRMS (ESI-TOF) calcd for C26H33N2OSi [M+H]+: 417.2362; Found: 417.2369. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In acetonitrile at 20℃; for 24h; | |
100% | With potassium carbonate In acetonitrile at 60℃; for 18h; | |
100% | With potassium carbonate In acetonitrile at 60℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With caesium carbonate In N,N-dimethyl-formamide at 20℃; | 2-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)phenoxymethyl]pyridine In a 50 mL round-bottomed flask, cesium carbonate (2.96 g, 9.09 mmol, Eq: 2.00), 4-(4,4,5,5- TETRAMETHYL- 1 ,3 ,2-DIOXABOROLAN-2- YL)PHENOL (1 g. 4.54 mmol, Eq: 1 .00 ) and 2- ( bromometh yl )pyrid i ne hydrobromide ( 1 . 1 5 g, 4.54 mmol, Eq: 1 .00) were combined with DMF (20 mL) to give a light yellow suspension. Let the reaction stir at rt overnight, concentrate the solution. Purify the compound by column ( Hcxanes EtOAc = 70 30) to afford the product 1 . 1 5 g(81%) MH+ 312.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; for 16h; | Intermediate 2-12. 5-Methyl-2-(pyridin-2-ylmethyl)-1 ,2,3,4-tetrahydroisoquinolin-6- olTo a solution of Intermediate 2-12-A (420 mg, 2.57 mmol) in CH2CI2 (12 mL) and triethylamine (1 .18 mL, 8.49 mmol) at 0 C was added 2-(bromomethyl)pyridine hydrobromide (781 mg, 3.09 mmol). The mixture was stirred at room temperature for 16 h, and then diluted with CH2CI2 and H20. The organic layer was separated. The aqueous layer was then extracted with CH2CI2. The organic layers were then combined and concentrated. The resulting residue was purified by silica gel flash column chromatography (heptane/EtOAc = 1 /0 to 0/1) to afford the title compound. MS (ESI+) m/z 255.2 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere; | 5.1 Synthesis of 2-((6-bromopyridin-3-yloxy)methyl)pyridine (5-1). To a solution of 6- bromopyridin-3-ol (0.5 g, 2.87 mmol) in N,N-dimethylformamide (30 mL) were added 2- (bromomethyl)pyridine hydrobromide (0.73 g, 2.87 mmol) and potassium carbonate (1.19 g, 8.62 mmol). The resulting mixture was stirred for 8 hours at ambient temperature under nitrogen atmosphere. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers was washed with brine (3 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 10-30% ethyl acetate in petroleum ether to afford 2-((6-bromopyridin-3- yloxy)methyl)pyridine as a red solid: MS (ESI, m/z): 265.0, 267.0 [M + 1]+; 1H MR (300 MHz, CDC13) δ 8.62 (d, J= 4.2 Hz, 1H), 8.16 (d, J= 3.0 Hz, 1H), 7.77-7.71 (m, 1H), 7.49 (d, J= 10.4 Hz, 1H), 7.38 (d, J= 11.7 Hz, 1H), 7.29-7.20 (m, 1H), 7.18-7.17 (m, 1H), 5.22 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; for 1h; | 2-(Bromomethyl)pyridine hydrobromide (CAS 31 106-82-8) (2.42 g, 9.56 mmol) was added to a mixture of 1 ,2,3,4-tetrahydroisoquinolin-6-ol hydrobromide (CAS 59839-23-5; 2 g, 8.69 mmol) and TEA (4.85 ml_, 34.8 mmol) in DCM (87 mL) at 0 C in four portions (30 min apart). The reaction mixture was allowed to warm to room temperature over 1 h. The reaction mixture was then partitioned between half saturated aq. NaHC03 and DCM. The mixture was passed through an ISOLUTE Phase Separator and the organic phase was concentrated. The resulting residue was purified by silica gel flash column chromatography (acetone/heptane, 0- 50% gradient) to give the title compound. MS (ESI+) m/z 241 .1 (M+H). | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;Inert atmosphere; | To a mixture of 1 ,2,3,4-tetrahydroisoquinolin-6-ol hydrobromide (CAS 59839-23-5, 2 g, 8.69 mmol) and TEA (4.85 mL, 34.8 mmol) in DCM (87 ml) at 0 C was added 2- (bromomethyl)pyridine hydrobromide (CAS 31 106-82-8, 2.42 g, 9.56 mmol) portionwise. The mixture was then stirred at rt for 1 h, and then diluted with 1 :1 water/saturated sodium bicarbonate and DCM. The mixture was then passed through an ISOLUTE Phase Separator. The organic phase was then concentrated. The resulting residue was purified by flash column chromatography (acetone/heptane, 0-50%) to afford title compound. MS (ESI+) m/z 241 .1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: 5-benzyloxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.75h; Inert atmosphere; Stage #2: 2-(bromomethyl)pyridine hydrobromide In N,N-dimethyl-formamide at 0 - 20℃; for 24h; Inert atmosphere; | 2.1.3. 5-(benzyloxy)-1-(pyridin-2-ylmethyl)-1H-indole (2) To a solution of 5-(benzyloxy)-1H-indole (4) (100 mg,0.45 mmol) in dry DMF (1.2 mL), NaH (21.5 mg, 0.54mmol) was added at 0 oC under argon. The reaction mixturewas stirred at that temperature for 45 min. 2-(Bromomethyl)pyridine hydro-bromide (135.9 mg, 0.54 mmol) wasadded and the mixture was stirred, from 0 oC to room temperature,under argon, for 24 h. The reaction was quenchedwith distilled water and extracted with EtOAc. The combinedorganic layers were washed with water and brine,dried over Na2SO4 anhydrous, filtered and concentrated. Thecrude was purified by flash chromatography (n-hexane/Et2O2:3) affording compound 2 in 84% yield (117.8 mg), as awhite solid; m.p. 115-117 oC (n-hexane/Et2O); 1H NMR (400MHz, CDCl3) 8.59 (d, J = 4.0 Hz, 1H, H15), 7.52 (t, J =7.7, 1H, H17), 7.47 (d, J = 7.3 Hz, 2H, H10), 7.39 (t, J = 7.3Hz, 2H, H11), 7.32 (t, J = 7.3 Hz, 1H, H12), 7.20 (d, J = 2.3Hz, 1H, H4), 7.18 (d, J = 3.2 Hz, 1H, H2), 7.17-7.15 (m, 2H,H7 and H16), 6.92 (dd, J = 8.9, 2.3 Hz, 1H, H6), 6.67 (d, J =7.8 Hz, 1H, H18), 6.51 (d, J = 3.2 Hz, 1H, H3), 5.43 (s, 2H,H13), 5.10 (s, 2H, H8); 13C NMR (101 MHz, CDCl3) 157.8(C14), 153.6 (C5), 149.5 (C15), 137.8 (C9), 137.2 (C17),131.8 (C7’), 129.3 (C3’), 129.2 (C2), 128.6 (2 x C11), 127.9(C12), 127.7 (2 x C10), 122.6 (C16), 120.8 (C18), 113.0(C6), 110.6 (C7), 104.4 (C4), 101.9 (C3), 71.0 (C8), 52.4(C13); IR (KBr) 3444, 1484, 1237, 1019 cm-1; HRMS (ESI)m/z 315.1495 [M+H]+ (calcd for C21H19N2O 315.1497); Purity100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 70℃; for 10h; | To a solution of <strong>[936250-20-3]3-methylpyrazole-4-boronic acid pinacol ester</strong> (1.40 g, 6.73 mmol) in DMF (40 mL) was added2- (bromomethyl) pyridine hydrobromide (2.5 g, 9.9 mmol), Cs2CO3 (3.91 g, 12.0 mmol) and KI (0.41 g, 2.4 mmol)The reaction was carried out at 70 C for 10 h. The reaction mixture was concentrated under reduced pressure to remove DMF, extracted with water (40 mL) and extracted with methylene chloride (50 mL × 3), and then the organicThe phases were dried over anhydrous Na2SO4. The concentrated crude product was isolated by silica gel column chromatography (eluent: PE / EtOAc (v / v) = 1 /1) to give 1.3 g of a yellow oil, yield: 65%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 100℃; for 10h; | To a solution of 4-bromo-3- (trifluoromethyl) -1H-pyrazole (1.01 g, 4.7 mmol) in DMF (40 mL)2- (bromineMethyl) pyridine hydrobromide (1.76 g, 6.96 mmol), Cs2CO3 (5.3 g, 16 mmol) and KI (0.4 g, 2 mmol)100 for 10h. The reaction mixture was concentrated under reduced pressure to remove DMF, extracted with water (40 mL) and extracted with methylene chloride (50 mL × 3), and then the organicThe phases were dried over anhydrous Na2SO4. The concentrated crude product was isolated by silica gel column chromatography (eluent: PE / EtOAc (v / v) = 1 /1) to give 1.2 g of a yellow oil, yield: 83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: ethyl 4-methyl-3-oxo-pentanoate With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: 3-methoxyphenyl isothiocyanate In N,N-dimethyl-formamide at 0 - 60℃; for 2h; Stage #3: 2-(bromomethyl)pyridine hydrobromide In N,N-dimethyl-formamide at 60℃; for 3h; | Ethyl 4-isopropyl-2-((3-methoxyphenyl)amino)-5-(pyridin-2-yl)thiophene-3-carboxylate (8aj) To a stirred solution of potassium carbonate (84 mg, 0.605 mmol) in DMF (0.5 mL) was added ethyl 4-methyl-3-oxopentanoate (0.10 mL, 0.605 mmol). After stirring at rt for 2 h, 3-methoxyophenyl isothiocyanate (0.08 mL, 0.605 mmol) was added dropwise at 0 °C. Then, the mixture was stirred at 60 °C for 2 h before addition of 2-(bromomethyl)pyridine hydrobromide (153 mg, 0.6053 mmol). The reaction mixture was stirred at 60 °C for 3 h and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated. The resulting crude residue was purified by column chromatography (ethyl acetate/Hex 10%) to give the thiophene 8aj (164 mg, 68% yield) a yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | To a stirred solution of potassium carbonate (84 mg, 0.605 mmol) in DMF (0.5 mL) was added methyl-3-cycloproyl-3-oxopropionate (0.07 mL, 0.6053 mmol). After stirring at rt for 2 h, 3-methoxyophenyl isothiocyanate (0.08 mL, 0.6053 mmol) was added at 0 C. Then, the mixture was stirred for 60 C for 2 h before addition of 2-(bromomethyl)pyridine hydrobromide (153 mg, 0.6053 mmol). The reaction mixture was stirred at 60 C for 3 h and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated. The resulting crude residue was purified by column chromatography (ethyl acetate/Hex 10%) to give the thiophene 8ak (186 mg, 81% yield) a yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2-Bromo-lH-imidazole (100 mg, 0.680 mmol) was dissolved in DMF (2 mL) in a microwave vial in an ice bath and purged with nitrogen for 10 min. With the solution at 0 C, sodium hydride (60% dispersion in mineral oil) (62.6 mg, 1.565 mmol) was added and the solution was stirred for 10 min under nitrogen. A solution of 2-(bromomethyl)pyridine hydrobromide (207 mg, 0.816 mmol) in DMF (2 mL) was added dropwise to the reaction mixture. Once all reagents were added, the reaction mixture was allowed to warm to RT and stirred for 2 days under an atmosphere of nitrogen. The solvent was removed under reduced pressure. The crude product was dissolved in ethyl acetate (20 mL) and washed with brine (20 mL). The solvent was again removed from the organic layer under reduced pressure. The samples were dissolved in 1: 1 MeOH:DMSO (3 mL) and purified by MDAP (Method B). The solvent was evaporated in vacuo to give the title compound. LCMS (System B): tRET = 0.63 min; MH+ 238, 240. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.8% | With caesium carbonate; In acetone; at 20℃; for 4h; | A mixture of tert- butyl 4-hydroxyphenethylcarbamate (1.03 g, 4.34 mol), cesium carbonate (3.88 g, 11.88 mmol) and 2-(bromomethyl)pyridine hydrobromide (1 g, 3.96 mmol) in acetone (20 mL) was stirred at room temperature for 4 h. The reaction mixture was filtrated. The filtrate was concentrated and purified by column chromatography (hexane :EtO Ac = 2: 1) to afford the title compound as white solid (1.18 g, 61.8% yield). 'H NMR (500 MHz, DMSO-riri) d: 8.58 (t, 1H), 7.82 (dt, 1H), 7.50 (d, 1H), 7.33 (t, 1H), 7.11 (d, 2H), 6.94 (d, 2H), 6.84 (t, 1H), 5.14 (s, 2H), (0149) 3.10 (q, 2H), 2.62 (t, 2H), 1.18 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Sodium hydrogenocarbonate; potassium carbonate In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere; | 5 Synthesis of Compound 7B A 100 mL four-necked round-bottomed flask was equipped with a magnetic stirrer bar, a condenser tube and a thermometer, purged with nitrogen, and then charged sequentially with bis[(2-diphenylphosphino)ethyl]amine hydrochloride (1.75 g, 3.95 mmoL, 1.0 equivalent), potassium carbonate (1.64 g, 11.9 mmoL, 3.0 equivalents), 2-(bromomethyl)-pyridine hydrobromide (18A) (1.0 g, 3.95 mmoL, 1.0 equivalent) and N,N-dimethylformamide (DMF) (10.5 mL). The resulting mixture was heated to 100°C. and stirred for 3 hours. After the reaction mixture was cooled to 5°C., ethyl acetate (EtOAc) (30 mL) and saturated aqueous sodium bicarbonate (30 mL) were sequentially added to separate the organic layer. After the aqueous layer was extracted twice with ethyl acetate (30 mL), the organic layers were combined and washed with saturated aqueous sodium chloride (30 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give the titled compound (7B) as a brown liquid crude product (0.67 g). 1H-NMR (400 MHz, CDCl3): δ=8.46-8.45 (m, 1H), 7.41-7.26 (m, 22H), 7.11-7.08 (m, 1H), 3.74 (s, 2H), 2.66-2.61 (m, 4H), 2.28-2.12 (m, 4H). 31P-NMR (161 MHz, CDCl3): δ=-7.8. HRMS (ESI, m/z) calculated for C34H34N2P2 ([M+H]+) 533.2270, found 533.2268. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium carbonate In acetonitrile at 25℃; for 48h; |
Tags: 31106-82-8 synthesis path| 31106-82-8 SDS| 31106-82-8 COA| 31106-82-8 purity| 31106-82-8 application| 31106-82-8 NMR| 31106-82-8 COA| 31106-82-8 structure
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P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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