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CAS No. : | 14389-86-7 | MDL No. : | MFCD00051940 |
Formula : | C14H12O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GMOYUTKNPLBTMT-UHFFFAOYSA-N |
M.W : | 228.24 | Pubchem ID : | 1810581 |
Synonyms : |
|
Num. heavy atoms : | 17 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.07 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 64.38 |
TPSA : | 46.53 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) : | -6.05 cm/s |
Log Po/w (iLOGP) : | 1.88 |
Log Po/w (XLOGP3) : | 2.31 |
Log Po/w (WLOGP) : | 2.81 |
Log Po/w (MLOGP) : | 2.8 |
Log Po/w (SILICOS-IT) : | 2.79 |
Consensus Log Po/w : | 2.52 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.97 |
Solubility : | 0.245 mg/ml ; 0.00107 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.93 |
Solubility : | 0.271 mg/ml ; 0.00119 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.44 |
Solubility : | 0.00827 mg/ml ; 0.0000362 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.84 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
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 |
---|---|---|
84.6% | To a suspension of 73 (4.0 g, 15.6 mmol) in H2O (150 ml) were added NaOH (3.1 g, 78.0 mmol) and EtOH (5 ml). The mixture was reflux for 12 h, and cooled to 25 C. The solid was filtered out and the filtrate was acidified with 2N HCl. The precipitate was collected and washed with H2O. The crude product was recrystallized from to give 78 as white solid. (3.0 g, 13.2 mmol). Yield: 84.6%; mp 73-75 C.; MS (EI, 70 eV): m/z 228.3 (M+); 1H-NMR (CDCl3, 200 MHz): delta 5.27 (s, 2H), 7.08-7.54 (m, 8H), 6.93 (dd, J=8.0, 1.8 Hz, 1H); 13C-NMR (CDCl3, 50 MHz) delta: 165.43, 157.40, 135.02, 134.34, 133.88, 129.16, 127.92, 122.44, 118.09, 113.11, 72.23; Anal. Calcd for C14H12O3: C, 73.67; H, 5.30. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine; dicyclohexyl-carbodiimide In dichloromethane 1.) 0 deg C, 1 h, 2.) RT 3 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxalyl dichloride;N,N-dimethyl-formamide; In tetrahydrofuran; at 0 - 20℃; for 0.5h; | To a stirring solution of 2-(benzyloxy)benzoic acid (2.55 g, 11.19 mmol) and oxalyl chloride (2.84 g, 22.39 mmol) in THF (20 mL) was added a few drops of DMF (0.012 mL, 0.153 mmol) at O0C. The reaction mixture was allowed to warm to room temperature and further stirred 30 minutes, diluted with toluene and then solvent evaporated. The residue was taken up in THF (20 mL) and to this solution was added 2-chloro-6- (trifluoromethyl)pyridin-3 -amine (2.0 g, 10.18 mmol) at OoC followed by the addition of triethylamine (4.68 mL, 33.6 mmol). The reaction mixture was allowed to stir 3 days at room temperature then quenched with saturated bicarbonate solution, extracted with EtOAc and solvent evaporated to afford title compound 72 (3.0 g, 73% yield) after purification by flash chromatography (0 to 100% ethyl acetate in hexane). LRMS(ESI): (calc) 406.07 (found) 407.4 (MH)+. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 0℃; for 2h; | To a solution of <strong>[14389-86-7]2-benzyloxybenzoic acid</strong> (1.14 g, 5.0 mmol, 1.0 equiv) in CH2Cl2 (50 mL) and a catalytic amount of DMF (2 drops) freshly distilled oxalyl chloride (472 muL, 6.0 mmol, 1.2 equiv) was slowly added via syringe at 0 C. The reaction was stirred for 2 hours then concentrated in-vacuo under reduced pressure. The crude acid chloride obtained was dissolved in ethanol-free anhydrous chloroform24 (50 mL) and N,O-dimethylhydroxylamine-HCl (0.5 g, 6 mmol, 1.2 equiv) was added. The reaction mixture was cooled to 0 C. and Et3N (20 mL) was added dropwise. The mixture was stirred at room temperature for 2.5 hours then concentrated in vacuo. The residue was partitioned between sat'd aq NaCl and 1:1 CH2Cl2/Et2O. The organic layer was dried (Na2SO4) and concentrated to afford the title compound (1.19 g, 80%) as an oil that was greater than 98% pure based on 1H NMR. Rf=0.3 (3:1 hexanes/EtOAc); 1H NMR (600 MHz, CDCl3) delta 3.23 (br s, 3H), 3.40 (br s, 3H), 5.09 (s, 2H), 6.55-6.95 (m, 2H), 7.29-7.40 (m, 7H); 13C NMR (150 MHz, CDCl3) delta 33.3, 61.4, 70.6, 112.9, 121.1, 127.3, 128.1, 128.6, 128.7, 129.2, 130.8, 137.0, 155.1, 169.5; MS (ESI+) calcd. for C16H18NO3 [M+H]+ 272.12, found 272.13. | |
To a solution of <strong>[14389-86-7]2-benzyloxybenzoic acid</strong> dry CH2Cl2 was added to 1 ml of freshly distilled oxalyl chloride. After stirring for 10 minutes, 1 drop of DMF was added to the reaction mixture. The reaction mixture was stirred for 2 hours at room temperature and the solvent was removed by evaporation. The resultant yellow oil was dried under vacuum for 3 hours. The yellow oil was then dissolved in 5 ml of dry xylenes and transferred via cannula to a solution of 3-aminosalacylic acid (g, 31.5 mmol) in xylenes. The mixture was stirred at room temperature for 1 h, then heated to reflux overnight. After the reaction mixture had cooled to room temperature, p-toluenesulfonic acid monohydrate (475 mg, 2.5 mmol) was added and the mixture heated to reflux for an additional 12 h. The reaction mixture was cooled to 0 C. and treated with an excess of TMSCHN2. The product was purified by column chromatography (20% EtOAc in hexane) to give a light yellow solid (42 mg, 36%): 1H NMR delta 4.04 (s, 3H, CH3), 7.00 (m, 1H), 7.10 (d, 1H, J=8.4 Hz), 7.4-7.5 (m, 2H), 7.87 (dd, 1H, J=8.1, 1.2 Hz), 7.97 (dd, 1H, J=7.5, 1.2 Hz), 8.06 (dd, 1H, J=8.1, 1.2 Hz); CIMS m/z 270 (MH+); HRMS m/z calc'd for C15H12NO4: 270.0763, found 270.0766. |
With thionyl chloride; In toluene; for 8h;Reflux; | To a suspension of 78 (3.1 g, 13.6 mmol) in dry toluene (150 ml)was added SOCl2 (12.9 g, 109.1 mmol). The mixture was reflux for 8 h and evaporated to give 83 as yellow liquid to use directly in the next step. (2.55 g, 10.3 mmol). Yield: 79.07%. | |
With thionyl chloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 20℃; for 12h; | General procedure: Preparation of arylcarbonyl chlorides (2a-f): Arylcarboxylic acids (1a-f) weresuspended in dry THF at room temperature. Thionyl chloride and DMF wereadded dropwise. The reaction mixtures were stirred for 12 h at roomtemperature and then evaporated to dryness. The residues were useddirectly in the next step without purification. | |
With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 20℃; for 2h; | 10415] Subsequently, 12.6 mE of oxalyl dichioride was added dropwise to a mixed solution of 32 g of 2-benzyloxy- benzoic acid, 0.2 mE of dimethylformamide, and 300 mE of tetrahydrofuran (also referred to as THF) at room temperature. This solution was stirred for 2 hours and then concentrated under reduced pressure to obtain <strong>[14389-86-7]2-benzyloxybenzoic acid</strong> chloride as a crude product. | |
Add 0.55 g(2.4 mmol, 1.2 eq) 2-benzyloxy-benzoic acid(compound 4a) and 7.25 ml disulfur dichloride to a dry one-necked flask. After stirring about 5 minutes, add two drops of pyridine. The reaction system was then heated to reflux for 2.5 hours; TLC showed no starting material existed. Then disulfur dichloride was removed by vacuum distillation to obtain a pale yellow wax-like solid (compound 5a). The crude product was used without purification in the next step directly. | ||
With thionyl chloride; In toluene; for 3h;Reflux; | A solution of 2-(benzyloxy)benzoic acid1 (10.00 g, 43.8 mmol) and thionyl chloride (6.4 mL, 10.44 g, 87.7 mmol) in toluene (90 mL) washeated under reflux for 3 h and then cooled and evaporated to give A (10.80 g, 100%) as a pale yellow oil which was used without furtherpurification. IR: 3032, 1780, 1599, 1448, 1290, 1024, 868, 759 cm-1. 1H NMR (400 MHz): delta = 8.09 (dd, J = 7.8, 1.8 Hz, 1 H), 7.53 (ddd, J =8.4, 7.4, 1.8 Hz, 1 H), 7.49-7.46 (m, 2 H), 7.40-7.35 (m, 2 H), 7.33-7.29 (m, 1 H), 7.06-7.02 (m, 2 H), 5.19 (s, 2 H, CH2). 13C NMR (100MHz): delta = 163.8 (C=O), 158.5 (C-O), 136.0 (CH), 135.8 (C), 134.5 (CH), 128.6 (2 CH), 128.0 (CH), 126.7 (2 CH), 122.8 (C), 120.6 (CH),113.5 (CH), 70.5 (CH2). HRMS (ESI+): m/z calcd for C14H11O2 [M-Cl]+: 211.0754; found: 211.0751. The 1H NMR spectral data was inaccordance with that previously reported.2 | |
With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 0 - 20℃; for 0.5h; | To a stirring solution of 2-(benzyloxy)benzoic acid (2.55 g, 11.19 mmol) and oxalyl chloride (2.84 g, 22.39 mmol) in THF (20 mL) was added a few drops of DMF (0.012 mL, 0.153 mmol) at 0 C. The reaction mixture was allowed to warm to room temperature and further stirred 30 minutes, diluted with toluene and then solvent evaporated. The residue was taken up in THF (20 mL) and to this solution was added 2-chloro-6-(trifluoromethyl)pyridin-3-amine (2.0 g, 10.18 mmol) at 0 C. followed by the addition of triethylamine (4.68 mL, 33.6 mmol). The reaction mixture was allowed to stir 3 days at room temperature then quenched with saturated bicarbonate solution, extracted with EtOAc and solvent evaporated to afford title compound 72 (3.0 g, 73% yield) after purification by flash chromatography (0 to 100% ethyl acetate in hexane). LRMS(ESI): (calc) 406.07 (found) 407.4 (MH)+. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In tetrahydrofuran; at 0 - 20℃; | To a stirring solution of 2-(benzyloxy)benzoic acid (2.55 g, 11.19 mmol) and oxalyl chloride (2.84 g, 22.39 mmol) in THF (20 mL) was added a few drops of DMF (0.012 mL, 0.153 mmol) at O0C. The reaction mixture was allowed to warm to room temperature and further stirred 30 minutes, diluted with toluene and then solvent evaporated. The residue was taken up in THF (20 mL) and to this solution was added 2-chloro-6-(trifluoromethyl)pyridin-3 -amine (2.O g, 10.18 mmol) at OoC followed by the addition of triethylamine (4.68 mL, 33.6 mmol). The reaction mixture was allowed to stir 3 days at room temperature then quenched with saturated bicarbonate solution, extracted with EtOAc and solvent evaporated to afford title compound 72 (3.0 g, 73% yield) after purification by flash chromatography (0 to 100% ethyl acetate in hexane). LRMS(ESI): (calc) 406.07 (found) 407.4 (MH)+. | |
With pyridine; thionyl chloride; for 2.5h;Reflux; | General procedure for the preparation of 6, 7, 9 and 10 A mixture of 4a (0.55?g, 2.4?mmol) in thionyl chloride (7.3?ml) and catalytic pyridine (0.04?ml) was stirred and refluxed for 2.5?h. After cooling to ambient temperature, the thionyl chloride was evaporated and the crude product 2-(benzyloxy)benzoyl chloride was obtained as light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.2% | With sodium hydroxide; In methanol; at 20℃; | Methyl 2-(benzyloxy)benzoate 2 (27 g, 106 mmol) was dissolved in MeOH (600 ml). 5N NaOH (424 mmol) was added with exothermic heating to 40 C. After the reaction mixture was stirred at RT overnight, it was acidified with a 5.5 N HCl solution (80 ml) (solution became clear) and concentrated in vacuum to form precipitate which was extracted with EA (300 ml). The organic layer was washed with water (45 ml) and brine (45 ml) and dried over Na2SO4. The solvent was evaporated to obtain 3 as solid (23.7 g). Yield: 98.2%. |
87.6% | With sodium hydroxide; In methanol; water; at 20℃; for 4.5h; | General procedure: To a solution of 3a or 3b (75 mmol) in methanol (75 ml) was added 4 M NaOH (aq) (75 ml) at room temperature. The reaction mixture was stirred at room temperature for 4.5 h. After the organic solvent methanol was evaporated, the residual was diluted with 2 M HCl (aq) at 0 oC. After the pH of the mixture was diluted to 5-6, the precipitate was collected by filtration, washed with water and dried under vacuum. 2-(benzyloxy)benzoic acid 4a, white solid, yield 87.6%. ESI-MS(m/z): 227.1[M-H]-. |
With sodium hydroxide; In ethanol; at 60℃; for 6h; | General procedure: 3a-3w were hydrolyzed using 20% NaOH in EtOH which was stirred at 60 C for 6 h. After reaction, the pH value of the solution was adjusted to 1-3 using 5 M hydrochloric acid. The mixture was extracted with CH2Cl2 for three times. The organic layer was combinedand dried with anhydrous Na2SO4 for 0.5 h to get 4a-4w. |
With sodium hydroxide; In methanol; water; at 20℃; for 4.5h; | 2. Synthesis of 2-benzyloxy-benzoic acid (Compound 4a) 18.17 g (75 mmol, 1.0 eq) 2-benzyloxy-benzoic acid methyl ester (compound 3a) was dissolved in 75 ml methanol and stirred uniformly. Then 75 ml sodium hydroxide aqueous solution (4 mol/L) was dropwise added at room temperature to the mixture. After 4.5 hours' reaction when the reaction system turn to the clear and transparent solution; TLC showed no starting material. Remove the methanol by vacuum distillation, add to the system 2M hydrochloric acid solution to regulate the pH value to 5?6 for solid to separate out. Then the solid was filtered and dried under vacuum to give 15.0 g of white solid, yield 87.6%. The crude product was used without purification in the next step directly. MS(ESI) (m/z): 227.1(M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | To ester25(1.60 mL, 12.04 mmol) in MeCN (50 mL) was added K2CO3(3.30 g, 24.08 mmol) followed by benzyl bromide (1.50 mL, 12.88 mmol) and the resulting mixture was stirred at reflux overnight. After cooling the reaction was diluted with water (25 mL) and the aqueous fraction extracted with DCM (3 × 20 mL). The combined organic extracts were washed with water (25 mL), dried over Na2SO4and solvent removed in vacuo. The crude residue was dissolved in 1,4-dioxane (50 mL) and aqueous NaOH (1.5 M, 12 mL) was added. The solution was stirred at reflux for 2 h, cooled to room temperature and the organic residues removed in vacuo. The remaining solution was acidified with 1M aqueous HCl, extracted with EtOAc (3 × 25 mL), the organic extracts dried over Na2SO4and solvent removed in vacuo to yield26(2.4 g, 82%) as a colourless solid, mp 70-71 C (lit. [63] mp 73-75 C). deltaH(CDCl3) 10.72 (1H, br s, OH), 8.21 (1H, dd,J= 7.8, 1.8 Hz, H-6), 7.56 (1H, ddd,J= 9.2, 7.4, 1.8 Hz, H-4), 7.46-7.38 (5H, m, Ar-H), 7.18-7.11 (2H, m, H-5, H-3) 5.30 (2H, s, CH2). deltaC(CDCl3) 165.6 (C = O), 157.6 (C), 135.2 (CH), 134.5 (C), 134.0 (CH), 129.34 (CH), 129.32 (2 × CH), 128.1 (2 × CH), 122.6 (CH), 118.2 (C), 113.3 (CH), 72.4 (CH2). LRMSm/z229.2 (100%, M + H). These data are in good agreement with literature values [64]. | |
76% | Compound 160:; [326] Potassium hydroxide (10.37 g, 184.8 mmol) was ground to a powder with a mortar and pestle and added to a 250 mL flask containing 75 mL of dimethyl sulfoxide and 2-hydroxy-benzoic acid methyl ester (7.03 g, 46.2 mmol). To this mixture was added benzyl bromide (7.91 g, 46.2 mmol) and allowed to mix for 4 hours with stirring. Water (100 mL) was added and the reaction stirred for an additional 30 minutes. The reaction was then cooled with an external ice bath to 0C and acidified with concentrated hydrochloric acid to a pH 1. The mixture was extracted with 3 x 230 mL ethyl acetate. The organic layers were combined and solvent removed under reduced pressure. The resulting yellow liquid was dissolved in ethyl acetate (50 mL) and washed with 2 X 30 mL water followed by 2 X 30 mL brine. The organic layer was dried over sodium sulfate, filtered, and solvent removed under reduced pressure. The resulting yellow liquid was dried under vacuum for several days, and white crystalline solid formed. The solid product was collected and dried further under vacuum. Product (8.04 g, 76%) was isolated as a white crystalline solid, mp 67-70C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Carbonyldiimidazole (CDI) (5.10 g, 31.5 mmol) was dissolved in 50 ml dry THF with stirring at room temperature under an argon atmosphere, and 2-(benzyloxy)benzoic acid (compound 2.4) (7.18 g, 31.5 mmol) was added to the mixture. After the evolution of CO2 ceased (ca. 5 min) the reaction mixture was stirred for an additional 10 minutes and <strong>[17672-21-8]methyl 2-amino-3-hydroxybenzoate</strong> (3.5 g, 21 mmol) was added. After stirring for an additional 10 minutes at room temperature, the reaction mixture was heated under reflux for 18 hours. The reaction mixture, brown in color, was concentrated and dissolved in a minimum volume of ethyl acetate (EtOAc). Silica gel (60-100 mesh) was added to make a slurry and solvent was evaporated to dryness. Column chromatography was performed using 20% EtOAc in hexane to give a light yellow solid (6.9 g, 87%): mp 104-105 C.; Rf 0.328 (20% EtOAc in hexanes); 1H NMR delta 3.80 (s, 3H), 5.50 (s, 2H), 7.05 (d, 1H, J=8.1 Hz), 7.10 (t, 1H), 7.24 (m, 2H), 7.34 (m, 3H), 7.47 (m, 3H), 7.61 (d, 1H, J=7.8 Hz), 8.27 (d, 1H, J=9.0 Hz), 9.28 (brs, 1H, NH), 12.27 (s, 1H, OH); 13C NMR delta 52.20, 70.80, 113.34, 120.94, 121.27, 121.58, 122.97, 125.70, 126.05, 126.93, 128.01, 128.21, 128.60, 132.69, 133.93, 136.22, 150.76, 157.01, 165.51, 167.57; CIMS m/z 378 (MH+); HRMS m/z calc'd for C22H20NO5: 378.1341, found 378.1343. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dicyclohexyl-carbodiimide; In tetrahydrofuran; at 0 - 20℃; for 2.5h; | N-Hydroxysuccinimdyl 2-benzyloxybenzoate. To a solution of <strong>[14389-86-7]2-benzyloxybenzoic acid</strong> (5.0 g, 21.9 mmol, 1.0 equiv) in THF (120 mL) at 0 C. was added N-hydroxysuccinimide (2.54 g, 21.9 mmol, 1.0 equiv) and DCC (4.53 g, 21.9 mmol, 1.0 equiv). The resulting mixture was stirred for 30 minutes at 0 C. then 2 hours at room temperature. The reaction mixture was filtered to remove the DCU precipitate and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (4:1 EtOAc/hexane) afforded the title compound (5.91 g, 82%) as a white solid. Rf=0.85 (EtOAc); 1H NMR (300 MHz, CDCl3) delta 2.87 (s, 4H), 5.22 (s, 2H), 6.98-7.12 (m, 2H), 7.22-7.42 (m, 3H), 7.44-7.60 (m, 3H), 8.20 (dd, 1H, J=7.8, 2.2 Hz); 13C NMR (CDCl3, 75 MHz) delta 26.1, 70.8, 114.0, 114.8, 120.8, 127.0, 128.0, 128.8, 133.0, 136.1, 136.3, 159.7, 164.9, 169.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone; for 4h;Heating / reflux; | To a solution of O-benzylsalycilic acid (5.0 g, 21.9 mmol, 1.0 equiv) in acetone (150 mL) was added solid K2CO3 (7.57 g, 54.8 mmol, 2.5 equiv) and MeI (2.05 mL, 32.9 mmol, 1.5 equiv) and the reaction heated at reflux for 4 hours. The reaction mixture cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (hexane/EtOAc) afforded the title compound (5.3 g, 100%) that was greater than 98% pure as judged by 1H NMR and was used without further purification. 1H NMR (600 MHz, CDCl3) delta 3.90 (s, 3H), 5.18 (s, 2H), 6.80-7.04 (m, 2H), 7.35-7.48 (m, 4H), 7.50 (d, 2H, J=7.8 Hz), 7.83 (d, 1H, J=7.6 Hz); 13C NMR (150 MHz, CDCl3) delta 52.2, 70.8, 114.1, 120.8, 121.1, 127.1, 128.0, 128.8, 132.0, 133.6, 137.0, 158.4, 167.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃; for 16h; | To a solution of 2- (phenylmethoxy)benzoic (1.0 g, 4.4 mmol), 3-bromopropan-l-ol (0.35 mL, 4.0 mmol), and 4- (dimethylamino) pyridine (50 mg) in 20 mL of anhydrous dichloromethane, 1-(3- dimethylaminopropyl) 3-ethylcarbodiimide hydrochloride (EDAC) (1.3 g, 6.6 mmol) was slowly added. The resulting mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCI three times followed by the addition of a saturated NaHC03 solution and brine. The organic layer was separated, dried through a MgS04 pad, and concentrated under reduced pressure. Chromatography (silica. gel, 1: 9 ethyl acetate/hexane) of the residue afforded 0.8 g (58%) of 3-Bromopropyl 2- (phenylmethoxy) benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 0 - 20℃; for 24h; | 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (EDAC) (1.3 g, 6.57 mmol) was slowly added to a solution of 2- (phenylmethoxy) benzoic acid (1.5 g, 6.57 mmol), 1-hydroxybenzotriazole (HOBt) (0.89 g, 6.57 mmol), and ethanolamine (0.40 mL, 6.57 mmol) in 50 mL of anhydrous THF at 0 C. The suspension was stirred and warmed up slowly to room temperature over 24 hrs. The reaction mixture was concentrated to dryness under reduced pressure and the resulting residue was diluted with dichloromethane and washed with 0.5N HCI twice followed by the addition of a saturated NaHC03 solution and brine. The organic layer was separated, dried through a MgS04 pad and concentrated under reduced pressure to afford 1.8 g (100%) of N-(2-Hydroxyethyl)[2-(phenylmethoxy)phenyl]carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃; for 48h; | To a solution of 2- (phenylmethoxy)benzoic (4.0 g, 17.5 mmol), (2R)-1-(tert-butyldimethylsiloxy)propan-2-ol (2.78 g, 14.6 mmol), and 4- (dimethylamino) pyridine (183 mg) in 100 mL of anhydrous dichloromethane, 1- (3-dimethylaminopropyl) 3-ethylcarbodiimide hydrochloride (EDAC) (4.2 g, 17.5 mmol) was slowly added. The resulting mixture was stirred at room temperature for 48 hrs. The reaction mixture was diluted with dichloromethane and washed with 0.5N HCI twice followed by the addition of saturated NaHC03 solution and brine. The organic layer was separated, dried through a MgS04 pad, and concentrated under reduced pressure. Chromatography (silica gel, 1:12 ethyl acetate/hexane) of the residue afforded 1.7 g (29%) of (1R)-1-Methyl-2-(tert- butyldimethylsiloxy) ethyl 2- (phenylmethoxy)benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32 g | 10414] A mixture of 50 g of salicylic acid, 136 g of benzyl bromide, 124 g ofpotassium carbonate, and 600 mE of acetonitrile was stirred with heating under reflux. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. To the residue thus obtained, 21.6 g of lithium hydroxide monohydrate, 200 mE of water, and 500 mE of methanol were added, followed by stirring at 100 C. The reaction mixture was concentrated under reduced pressure and the residue was acidified with 5% dilute hydrochloric acid, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 32 g of 2-benzyloxybenzoic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.87% | L-Threonine methyl ester·HCl ((2S,3R)-methyl 2-amino-3-hydroxybutanoate), 4, (6.27 g, 41.14 mmol) was dissolved in DCM (480 ml) and triethylamine (4.15 g, 41.14 mmol, 5.7 ml) was added. The reaction mixture was stirred at RT for 10 min and 2-(benzyloxy)benzoic acid 3 (9.045 g, 39.67 mmol) was added. The solution was cooled to 0 C. and HOBt (0.54 g, 4 mmol) and DIC (6.26 g, 49.58 mmol, 7.76 ml) were added. The reaction mixture was stirred overnight at RT and a precipitate (diisopropyl urea) was observed. The reaction mixture was diluted with DCM (200 ml), washed with water (200 ml), saturated NaHCO3 (200 ml), 5% citric acid (200 ml), water (200 ml) and brine (200 ml) and dried over Na2SO4. The organic solvent was evaporated in vacuum and the crude residue dissolvend in EA (100 ml) and a precipitate of diisopropyl urea was filtered out (3 g). The organic filtrate was evaporated to obtain dark yellow oil (17 g), which was purified by flash chromatography: SiO2 (400 ml), CHCl3, 2% MeOH in CHCl3to obtain 11.27 g of 5 as oil. Yield: 82.87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | [2-(Benzvloxv)-phenvl1-carbamic acid 2-trimethvlsilanyl-ethvl ester 2-(Benzyloxy) benzoic acid (5.064g, 22. 2mmol), diphenylphosphoryl azide (7.2mL, 33. 4mmol, 1.5eq) and triethylamine (4.6mL, 33. 4mmol, 1.5eq) were heated in toluene (44mL, 0.5M) at 80C for 30 minutes. Trimethylsilyl ethanol (6.4mL, 44. 4mmol) was added and heating was continued for 24 hours (complete after 1 hr). Upon cooling, the mixture was diluted with ethyl acetate and washed sequentially with 2M HCI and saturated sodium bicarbonate, dried (Na2SO4), filtered and concentrated. The residue was purified by chromatography on silica gel with iso-hexane containing ethyl acetate (1-3%) to yield the title compound (6.440g, 85%) as a colourless oil. 'H NMR (CDCI3) 8H : 0.00 (9H, s), 0.94-1. 05 (2H, m), 4.13-4. 27 (2H, m), 5.04 (2H, s), 6.81- 6.97 (3H, m), 7.15 (1H, s), 7.25-7. 41 (5H, m), 8.06 (1H, br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | General procedure: Magnesium turnings (4.0 equiv) were placed in a dry round bottom flask and flame-dried under a steady stream of argon. Upon cooling of the flask to room temperature, anhydrous THF and one drop of 1,2-dibromoethane were added to the flask. The contents were allowed to react for 5 min followed by addition of the appropriate bromide (as a solution in anhydrous THF) over a period of 5 min. The Grignard reagent was allowed to form for 2.5 h and was quenched with dry ice. This was followed by addition of 10% hydrochloric acid (10 mL). The contents from the reaction quench were transferred to a separatory funnel, followed by addition of ethylacetate (20 mL). The aqueous phase was extracted with ethylacetate (3 × 20 mL). The combined organic extracts were treated with 5% sodium hydroxide (3 × 5 mL). Concentrated hydrochloric acid was added to the combined aqueous phase until the pH of the solution was 2.5, which resulted in the precipitation of the product. Filtration of the precipitate yielded the desired carboxylic acid in 45-78% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.2% | EDCI (0.230 g, 1.20 mmol) at r.t., was added portionwise to a stirred slurry of 2-(benzyloxy)benzoic acid (0.250 g, 1.10 mmol) and Pfp-OH (0.222 g, 1.20 mmol) dissolved in dichloromethane (2 mL) over a period of 5 minutes at r.t. The resulting slurry was stirred at r.t. for 3 hours after which a solution formed. The resulting solution was added dropwise to methylhydrazine (0.175 mL, 3.29 mmol) in dichloromethane (2 mL) at r.t. over 5 minutes. The reaction mixture was purified by preparative HPLC using a Gemini NX reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 ml / minute) using an isocratic mixture of 28% acetonitrile in water (containing ammonium carbonate (2 g / L). The fractions containing the desired compound were evaporated to dryness to afford 2-(benzyloxy)-N-methylbenzohydrazide (21a, 0.200 g, 71.2 %) as a clear colourless gum: LCMS (tR = 2.06 min., purity = 100%), ESI+ m/z, 256.90 (M+H)+; 1H NMR (500 MHz, DMSO) delta (ppm) v. complex 1.1 mixture of rotamers 7.51-7.14 (m, 9H, 5.26 - 5.17 (br m, 3H), 4.61 (s, 1H), 3.13 (s, 1.5 H), 2.82 (s, 1.5 H); 13C NMR (126 MHz, DMSO-d6) delta (ppm) 169.85 / 164.95, 154.42, 137.72 / 137.30, 130.72, 129.41, 128.88 / 128.77, 128.32 / 128.13, 127.96 / 127.84, 127.59 / 127.35, 126.30, 121.23, 120.55, 113.26 / 112.75, 69.69, 37.89. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Coupling general procedure 4Ar2-COOH (1.Seq), HBTU (1.4 eq), HOBT (1.Seq) dissolved in DMF (20m1/mmol)were stirred at 25C for 0.Shours, then intermediates 12-17 (leq.) and DIPEA (3eq.) dissolved in DMF(lOml/mmol) were added. After 18 hours solvents were evaporated; residue poured in an aqueous saturated solution of NaHCO3 and extracted with dichloromethane. The crude was purified by silica gel column chromatography (DCM /AcOEt=9/1 to AcOEt 1 00%)According to generalprocedure 1, 2, 3 or 4 the following compounds 1-49 were prepared: | |
General procedure: Ar2-COOH (1.5eq), HBTU (1.4 eq). HOBT (1.5eq) dissolved in DMF (20 ml/mmol) were stirred at 25 C. for 0.5 hours, then intermediates 12-17 (1eq.) and DIPEA (3 eq.) dissolved in DMF (10 ml/mmol) were added. After 18 hours solvents were evaporated; residue poured in an aqueous saturated solution of NaHCO3 and extracted with dichloromethane. The crude was purified by silica gel column chromatography (DCM/AcOEt=9/1 to AcOEt 100%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | General procedure: 5.1.3. General procedure C. To the carboxylic acid substrate (0.42 mmol, 1.2 equiv) in DMF (1.5 mL) was added CDI (0.50 mmol, 1.1equiv) and DBU (0.67 mmol, 1.9 equiv). The reaction was stirred for 30 min at 23 C. Next, 2-amino-4-(2-pyridyl)thiazole 20 (0.35 mmol, 1.0 equiv) was added and the reaction mixture was stirred for 16 h at 23 C. A small amount of silica gel was added to the reaction mixture, which was concentrated in vacuo under reduced pressure. The crude product impregnated on the silica gel was purified by silica gel flash chromatography (0-10% MeOH-CH2Cl2) to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | General procedure: Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (pyBOP) (2.2 mmol) was added to a solution of 2,3-dimethoxybenzoic acid 46 (2.2 mmol) or 2-benzyloxysalicylic acid 53 (2.2 mmol) in dry dichloromethane (20 mL). After 5 min, triethylamine (TEA) (2 mmol) and the corresponding diamine (1 mmol) were added. The mixture was stirred at room temperature overnight and then evaporated to dryness. The residue was dissolved in ethyl acetate (30 mL) and washed successively with saturated solutions of citric acid (3 x 20 mL), NaHCO3 (3 x 20 mL) and NaCl (1 x 20 mL). The residue was concentrated and purified by preparative centrifugal circular thin-layer chromatography (CCTLC) using dichloromethane/methanol (9:1?1:1) as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (pyBOP) (2.2 mmol) was added to a solution of 2,3-dimethoxybenzoic acid 46 (2.2 mmol) or 2-benzyloxysalicylic acid 53 (2.2 mmol) in dry dichloromethane (20 mL). After 5 min, triethylamine (TEA) (2 mmol) and the corresponding diamine (1 mmol) were added. The mixture was stirred at room temperature overnight and then evaporated to dryness. The residue was dissolved in ethyl acetate (30 mL) and washed successively with saturated solutions of citric acid (3 x 20 mL), NaHCO3 (3 x 20 mL) and NaCl (1 x 20 mL). The residue was concentrated and purified by preparative centrifugal circular thin-layer chromatography (CCTLC) using dichloromethane/methanol (9:1?1:1) as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | General procedure: Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (pyBOP) (2.2 mmol) was added to a solution of 2,3-dimethoxybenzoic acid 46 (2.2 mmol) or 2-benzyloxysalicylic acid 53 (2.2 mmol) in dry dichloromethane (20 mL). After 5 min, triethylamine (TEA) (2 mmol) and the corresponding diamine (1 mmol) were added. The mixture was stirred at room temperature overnight and then evaporated to dryness. The residue was dissolved in ethyl acetate (30 mL) and washed successively with saturated solutions of citric acid (3 x 20 mL), NaHCO3 (3 x 20 mL) and NaCl (1 x 20 mL). The residue was concentrated and purified by preparative centrifugal circular thin-layer chromatography (CCTLC) using dichloromethane/methanol (9:1?1:1) as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydrogencarbonate; In isopropyl alcohol; acetone; at 80℃; for 16h; | Step 1 O-Benzylsalicylic acid (2.2 g, 10 mmol, 1 eq.) is dissolved in an isopropanol (22 mL)/acetone (33 mL) mixture. A catalytic amount of NaHCO3 (42 mg, 0.5 mmol, 0.05 eq.) and 2,3- epoxypropyltrimethylammonium chloride (1.51 g, 10 mmol, 1 eq.) are then added at room temperature, and the reaction mixture is heated at 80C for 16 hours. The reaction mixture is concentrated under reduced pressure and the residue is purified by chromatography on silica gel (CH2Cl2/MeOH: 10/1) to isolate the benzyl intermediate A in the form of a white solid (2.5 g, 73% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.23% | With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; | General procedure: 4.2.4 General synthetic procedure of salicylic acid derivatives containing metronidazole (5a-5w) Met-OTs (2 mmol), 4a-4w (2 mmol) and K2CO3 (4 mmol) were added in DMF (20 mL). The reaction was stirred at 110 C for 20-24 h. The reaction mixture was poured into water and extracted with ethyl acetate (3 * 50 mL). The organic layer was combined and dried with anhydrous Na2SO4 for 0.5 h. Column chromatography was performed using silica gel (200-300 mesh) eluting with ethyl acetate and petroleum ether to obtain the desired compounds (5a-5w). 4.2.4.1 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)-ethyl-2-(benzyloxy)benzoate (5a) Yellow solid, yield: 63.23%, mp: 78-80 C. 1H NMR (400 MHz, CDCl3) delta: 2.43 (s, 3H, CH3), 4.68 (s, 4H, CH2), 5.19 (s, 2H, CH2), 7.02-7.07 (m, 2H, ArH), 7.36-7.40 (m, 1H, ArH), 7.42 (s, 1H, ArH), 7.44 (d, J = 5.80 Hz, 2H, ArH), 7.47-7.48 (m, 1H, ArH), 7.50-7.52 (m, 1H, ArH), 7.73-7.75 (m, 1H, ArH), 7.93 (s, 1H, ArH). MS (ESI): 381.38 (C20H20N3O5, [M+H]+). Anal. Calcd for C20H19N3O5: C, 62.99; H, 5.02; N, 11.02. Found: C, 63.12; H, 5.01; N, 11.04. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.9% | D-Threonine methyl ester?HCl ((2R,38)-methyl 2-amino-3-hydroxybutanoate), 11, (13.94 g, 82.24 mmol) was dissolved in DCM (960 ml) and triethylamine (8.3 g, 82.24 mmol, 11.4 ml) was added. The reaction mixture was stirred at RT for 10 min and 2-(benzyloxy)benzoic acid 3(18.09 g, 79.34 mmol) was added. The solution was cooled to 0 C. and HOBt (1.08 g, 8 mmol) and DIC (12.51 g, 99.16 mmol, 15.5 ml) were added. The reaction mixture was stirred overnight at RT and a precipitate (diisopropyl urea) was observed. The reaction mixture was diluted with DCM (400 ml), washed with water (400 ml), saturated NaHCO3 (400 ml), 5% citric acid (400 ml), water (400 ml) and brine (400 ml) and dried over Na2SO4. The organic solvent was evaporated in vacuum and the residue dissolvend in EA (200 ml) and a precipitate of diisopropyl urea was filtered out (5 g). The organic filtrate was evaporated to obtain dark yellow oil (35 g). The crude product was purified by flash chromatography: SiO2 (600 ml), CHCl3, 2% MeOH in CHCl3 to obtain 23.6 g of 12 as oil. Yield: 92.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With palladium(II) trifluoroacetate; silver carbonate In 1,4-dioxane; dimethyl sulfoxide at 120℃; for 12h; Sealed tube; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | (1-Methyl-2-nitro-1H-imidazol-5-yl)methanamine (21). To aldehyde20(0.60 g, 3.87 mmol) in MeOH (16 mL) was added ammonium acetate (5.96 g, 77.4 mmol) and the mixture was stirred at 45 C for 2 h. NaCNBH4(0.17 g, 2.37 mmol) was added and the mixture stirred for 48 h, acidified to pH 1 with 6 M aqueous HCl and solvent removed in vacuo. The aqueous residue was filtered and the filtrate basified to pH 14 with 6 M aqueous KOH. The aqueous was extracted with DCM (3 × 50 mL), then saturated with NaCl and further extracted with DCM (3 × 50 mL). The combined organic fractions were concentrated and filtered through a plug of silica (9:1, DCM, MeOH) to give a crude residue21(0.15 g) which was used without further purification. deltaH((CD3)2SO) 7.07 (1H, s, H-4), 3.90 (3H, s, CH3), 3.77 (2H, s, CH2), 3.17 (2H, br s, NH2). To benzoic acid26(0.16 g, 0.704 mmol) in DCM (3 mL) was added oxalyl chloride (0.30 mL, 3.54 mmol) and the mixture was stirred overnight at room temperature. Solvent was removed in vacuo. The crude residue was taken up in DCM (2 mL) and added to a solution of amine21(0.10 g, 0.64 mmol) in pyridine (2 mL) at 0 C. The mixture was allowed to come to room temperature and stirred for 4 h. Solvent was removed in vacuo and the crude residue was purified by column chromatography (2:1, EtOAc, X4) to yield7(0.16 g, 70%) as yellow solid, mp 120-122 C. deltaH((CD3)2SO) 8.62 (1H, t,J= 5.5 Hz, NH), 7.67 (1H, dd,J= 7.6, 1.7 Hz, H-6), 7.49-7.43 (1H, m, H-4), 7.42-7.38 (2H, m, Ar-H), 7.33-7.26 (3H, m, Ar-H), 7.22 (1H, d,J= 7.8 Hz, H-3), 7.07-7.02 (2H, m, H-5, H-4?), 5.19 (2H, s, OCH2), 4.55 (2H, d,J= 5.6 Hz, NCH2), 3.75 (3H, s, NCH3). deltaC((CD3)2SO) 165.5 (C = O), 155.8 (C), 145.4 (C), 136.4 (C), 136.0 (C), 132.1 (CH), 130.0 (CH), 128.3 (2 × CH), 127.9 (CH), 127.6 (2 × CH), 127.2 (CH), 123.8 (C), 120.7 (CH), 113.3 (CH), 70.0 (CH2), 33.9 (CH3), 33.1 (CH2). HRMS calcd for C19H19N4O4(M + H)m/z367.1401, found 367.1407. LRMSm/z367.2 (100%, M + H). HPLC purity: 99.3% (effector6: not detected). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | To ketone23(0.20 g, 1.2 mmol) in MeOH (4 mL) was added ammonium acetate (1.8 g, 23.6 mmol) and the resulting solution was stirred at 40 C for 1 h. Activated 4 A molecular sieves were added and the mixture was stirred a further 1 h. The mixture was cooled to 0 C and NaCNBH4(0.05 g, 0.84 mmol) added, then the mixture was warmed to room temperature and stirred overnight. Solvent was removed in vacuo and the resulting residue filtered through a plug of silica (9:1, DCM, MeOH) to give a crude residue 24 (0.04 g) which was used without further purification. deltaH((CD3)2SO) 7.10 (1H, s, H-4), 4.05 (1H, q,J= 6.7 Hz, CH), 3.94 (3H, s, NCH3), 1.38 (3H, d,J= 6.7 Hz, CH3). To benzoic acid26(0.06 g, 0.26 mmol) in DCM (1 mL) added oxalyl chloride (0.11 mL, 3.54 mmol) and the mixture was stirred overnight at room temperature. Solvent was removed in vacuo. The crude residue was taken up in DCM (1 mL) and added to a solution of amine24(0.04 g, 0.24 mmol) in pyridine (0.5 mL) at 0 C. The mixture was allowed to come to room temperature and stirred overnight. Solvent was removed in vacuo and the crude residue was purified by column chromatography (2:1, X4, EtOAc) to yield8(0.026 g, 29%) as a white solid, mp 151-153 C. deltaH(CDCl3) 8.22 (1H, dd,J= 7.8, 1.8 Hz, H-6), 8.08 (1H, d,J= 8.2 Hz, NH), 7.54-7.50 (1H, m, H-4), 7.43-7.28 (5H, m, Ar-H), 7.15 (1H, td,J= 7.2, 1.0 Hz, H-5), 7.10 (1H, d,J= 8.3 Hz, H-3), 6.81 (1H, d,J= 0.6 Hz, H-4?), 5.36 (1H, p,J= 8.0 Hz, CH), 5.08 (2H, ddd,J= 10.8, 9.8, 9.8 Hz, OCH2), 3.84 (3H, s, NCH3), 1.44 (3H, d,J= 6.9 Hz, CH3). deltaC(CDCl3) 164.5 (C = O), 157.1 (C), 139.3 (C), 135.0 (C), 133.7 (CH), 132.7 (CH), 129.5 (CH), 129.2 (2 × CH), 128.4 (2 × CH), 126.0 (CH), 122.2 (CH), 120.8 (C), 112.5 (CH), 71.9 (CH2), 39.8 (CH), 34.4 (CH3), 19.5 (CH3); C-NO2was not observed. HRMS calcd for C20H21N4O4(M + H)m/z381.1571, found 381.1568. LRMSm/z381.2 (100%, M + H). HPLC purity: 99.8% (effector6: not detected). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 12h;Inert atmosphere; | General procedure: To a solution of an appropriate acid (0.12mmol) and related amine or alcohol (0.10mmol) in an anhydrous CH2Cl2 (50mL) was added EDC·HCl (0.13mmol) and DMAP (0.01mmol) at 0C under N2 atmosphere. Then the mixture was stirred at room temperature for 12h. The mixture was diluted with CH2Cl2, washed with 1M HCl, saturated NaHCO3 and brine, dried over Na2SO4. After the solvent was distilled off under reduced pressure, the resulting residues were purified by flash chromatography to furnish compounds 25-32, 34-36, 39-40, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.5% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | Flavonoid derivative b (678mg, 1mmol), o-benzyloxybenzoic acid a (273.6mg, 1.2mmol), DMAP (183mg, 1.5mmol) were added to a 100ml single-necked flask, 25ml DMF was added, the system was in a suspended state, and EDCI was finally added (287mg, 1.5mmol), the system slowly dissolved after 1-2 hours, stirred at room temperature overnight for 14h, the reaction was detected by TLC, after the basic reaction of the raw materials was completed, the system was poured into water, a yellow solid precipitated, suction filtration, and column chromatography Purified, added petroleum ether, sonicated, slurried at room temperature, and filtered to obtain 600 mg of a yellow solid with a yield of 67.5%. |
Tags: 14389-86-7 synthesis path| 14389-86-7 SDS| 14389-86-7 COA| 14389-86-7 purity| 14389-86-7 application| 14389-86-7 NMR| 14389-86-7 COA| 14389-86-7 structure
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
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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