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CAS No. : | 55499-44-0 | MDL No. : | MFCD02683101 |
Formula : | C8H11BO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | TYONHSPZXLFWKI-UHFFFAOYSA-N |
M.W : | 149.98 | Pubchem ID : | 4198739 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.25 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 46.2 |
TPSA : | 40.46 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.11 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.56 |
Log Po/w (WLOGP) : | -0.02 |
Log Po/w (MLOGP) : | 0.94 |
Log Po/w (SILICOS-IT) : | 0.15 |
Consensus Log Po/w : | 0.53 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.09 |
Solubility : | 1.22 mg/ml ; 0.00812 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.02 |
Solubility : | 1.43 mg/ml ; 0.00956 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.04 |
Solubility : | 1.36 mg/ml ; 0.00904 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.44 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P270-P273-P301+P312-P330 | UN#: | N/A |
Hazard Statements: | H302-H413 | 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 |
---|---|---|
15.4 g | Stage #1: With magnesium In tetrahydrofuran for 2 h; Inert atmosphere Stage #2: With hydrogenchloride In water |
Magnesium in a reaction vessel equipped with a dropping funnel 3.42 g (0.140 mol) was added tetrahydrofuran 9 mL. After nitrogen purging the system was added dropwise a solution of the equation (I-4-1) with the compound represented by 20.0 g (0.108 mol) in tetrahydrofuran 60 mL, to prepare a Grignard reagent. After stirring for 2 hours, it was added dropwise trimethyl borate 14.6 g (0.140 mol). After stirring for 2 h, and stirred for 1 h with hydrochloric acid. By the separation process to the organic layer and distilling off the solvent was washed with brine, to give a formula (I-4-2) with the compound represented by 15.4 g (0.103 mol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In water; N,N-dimethyl-formamide; at 80℃; for 3h;Inert atmosphere; | General procedure: A mixture of 4-chloro-2-methylsulfanyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (46, 54 mg, 0.152 mmol), 2-methyl-4-fluorophenylboronic acid (30 mg, 0.198 mmol), Pd2Cl2(PPh3)2 (5 mg, 0.0076 mmol), NaHCO3 aqueous solution (1 M, 0.46 ml, 0.456 mmol) and DMF (3 mL) was degassed by bubbling N2 through the mixture for 5 min. The reaction was then heated under a nitrogen atmosphere at 80 C for 3 h. The mixture was allowed to cool and was then partitioned between EtOAc (2 × 15 mL) and brine (15 mL). The combined organics were passed through a hydrophobic frit and evaporated in vacuo. The crude product was purified by flash chromatography on SiO2 (20 g) eluting with hexane-20% EtOAc/hexane (gradient) to afford the title compound 15b (54 mg, 83%) as a colourless solid. | |
With sodium hydrogencarbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 80℃; for 2.33333h; | Step24-(2,4-dimethyl-phenyl)-2-methylsulfanyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H- pyrrolo[2,3-d]pyrimidineA mixture of 4-chloro-2-methylsulfanyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H- pyrrolo[2,3-d]pyrimidine (2.04 g; 6.19 mmol), 1N sodium hydrogen carbonate (aq) 18.6 ml; 18.6 mmol), DMF (41 ml) and <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> was degassed by bubbling nitrogen through reaction mixture for 5 minutes. Dichlorobis(triphenylphosphine) palladium(ll) (217 mg; 0.309 mmol) was added and reaction mixture was heated to 8O0C for 2.25 hours under nitrogen atmosphere. Reaction mixture was allowed to cool to ambient temperature and then filtered through a pad of celite. The filter cake was washed with methanol and ethyl acetate and combined filtrate solvents were removed in vacuo and the residue partitioned between ethyl <n="27"/>acetate (100ml) and sat. sodium chloride (aq) solution (100 ml). The organic phase was dried over Na2SO4 then filtered and filtrate solvents evaporated in vacuo. The crude product was purified by flash chromatography on silica gel (5Og) eluting with a solvent gradient of 0 to 10% ethyl acetate in hexane to afford product as a yellow oil, (2.01 g). LC/MS: RT = 3.06 min; m/z = 400 [M+H]+. Total run time 3.75 mins. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; water; at 120℃; for 0.416667h; | Step 92-Chloro-4-(2,4-dimethyl-phenyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H- pyrrolo[2,3-d]pyrimidine-5-carbonitrileA mixture of 2,4-dichloro-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrirnidine- 5-carbonitrile (75 mg; 0.22 mmol), <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (49 mg; 0.33 mmol), Pd(dppf)CI2 (10 mg; 0.012 mmol), K2CO3 (90 mg; 0.65 mmol) and THF/ H2O (10:1 ; 2 ml) was degassed by bubbling N2 through the mixture for 5 min. The reaction was then <n="43"/>microwaved at 120 0C for 20 minutes. The mixture was allowed to cool and was then partitioned between EtOAc (2 x 20 ml) and brine (20 ml). The combined organics were dried over Na2SO4 then filtered and the filtrate solvents evaporated in vacuo. The crude product was purified by flash chromatography on SiO2 (10 g) eluting with 10% EtOAc/Hexane to afford the desired product as a white solid (40 mg; 44%). LC/MS: RT = 2.91 min; m/z = 415, 413 [M+H]+. Total run time 3.75 mins. 1H NMR (d6 DMSO): delta 0.00 (s, 9H); 0.94 (t, 2H); 2.27 (s, 3H); 2.45 (s, 3H); 3.68 (t, 2H); 5.73 (s, 2H); 7.25 (d, 1H); 7.30 (s, 1H), 7.40 (d, 1H); 8.89 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium fluoride;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; at 80℃; for 2h;Heating / reflux; | Bis(tri-t-butylphosphine)palladium(0) was added to a suspension of 4-Chloro-1 H- Pyrrolo[2,3-b]pyridine, 2,4-Dimethylphenylboronic acid and potassium fluoride in 1 ,4- Dioxan under a nitrogen atmosphere. The reaction mixture heated at -800C, for ~ 2hrs. The suspension was allowed to cool and diluted with ethyl acetate, the phases were separated and the organic phase was washed with water, saturated aqueous sodium chloride solution, then dried over anhydrous sodium sulphate and concentrated to a pale yellow solid. The crude product was purified by column chromatography on silica gel, eluting with mixtures of dichloromethane and methanol. The resulting product was re- purified by column chromatography on silica gel , eluting with mixtures of ethyl acetate and hexane, to afford title compound as a pale yellow solid. LCMS retention time = 2.468 minutes; m/z = 233.1 [M+H]+ (Run time 3.75mins) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.55% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; | A mixture containing 0.40 g (1.72 mmol) of 3-bromo-1- methyl-5-nitropyridin-2(lH)-one, 0.39 g (2. 60 mmol) of 2,4- dimethylphenyl boronic acid, 0.70 g (5.06 mmol) of potassium carbonate, 0.31 ml (17.22 mmol) of water, and 0.99g (0.86 mmol) of tetrakis(triphenylphosphine)palladium(0) in 80 ml of dioxane was heated to 90C under a nitrogen atm. overnight. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 60% ethyl acetate/hexanes gave 0 . 37 g (82.55%) of product. ¹H NMR (CDC13) 5: 2.19 (s, 3H) , 2.35 (s, 3H) , 3.71 (s, 3H) , 7.03 - 7 . 09 (m, 3H) , 8 . 06 (d, J = 3.2 Hz, 1H) , 8 . 66 (d, J = 3.2 Hz, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; for 16h;Heating / reflux; | To a solution of 8-bromo-2-methyl-2H-1,4-benzoxazin- 3(4H)-one (1.20 g, 4.96 mmol) in 1,2-dimethoxyethane (50 ml) were added <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (818 mg, 5.45 mmol), tetrakis(triphenylphosphine)palladium(0) (286 mg, 0.245 mmol ) and 2M sodium carbonate solution (4.96 ml, 9.92 mmol) . The mixture was refluxed for 16 h and diluted with water. The aqueous solution was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography eluting with 20 % ethyl acetate/n-hexane to afford 1.20 g (91 %) of the title compound. ¹H-NMR (CDC13) No.: 1.50 (dd, J = 6.8 Hz, 1.2 Hz, 3H), 2.15 (s, 3H), 2.37 (s, 3H), 4. 60-4. 65 (m, 1H), 6.80-6.90 (m, 2H), 6.95-7.02 (m, 1H), 7.05-7.10 (m, 3H), 9.01 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 90℃; for 18h; | To a mixture of 2-dipropylamino-3-methyl-4-oxo-3,4- dihydro-quinazolin-5-yl-trifluoromethanesulfonate (87 mg, 0.21 mmol), 2,4-dimethylphenylboroic acid (64 mg, 0.427 mmol) and potassium carbonate (59 mg, 0.43 mmol) and toluene (2 ml) was added of tetrakis(triphenylphosphine)palladium(0) (47 mg, 0.0405 mmol). The mixture was stirred at 90 C for 18 h and diluted with water. The aqueous solution was extracted with ethyl acetate. The extract was washed with saturated sodium bicarbonate solution in water, 10% citric acid solution in water and brine, dried over magnesium sulfate, and concentrated under vacuum. The residue was purified by column chromatography eluting with 5% ethyl acetate/n- hexane to afford 55 mg (71 %) the title compound. ¹H-NMR (CDC13) No.: 0.85-0.92 (6H, m), 1.55-1.68 (4H, m), 2.01 (3H, s), 2.37 (3H, s), 3.13-3.20 (4H, m), 3.42 (3H, s), 6.95-7.10 (4H, m), 7.49 (lH, d, J = 8.4 Hz), 7.55-7.62 (lH, m) . MS Calcd.: 363; Found: 364 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 90℃; for 18h; | To a mixture of [1-(2-ethylbutyl)-3-methyl-2,4-dioxo- 1,2,3,4-tetrahydro-quinazolin-5- yl] trifluoromethanesulfonate (29 mg, 0.071 mmol), 2,4- dimethylphenylboroic acid (21 mg, 0.14 mmol) and potassium carbonate (20 mg, 0 . 14 mmol) and toluene (2 ml) was added of tetrakis (triphenylphosphine)palladium(0) mg, 0.036 mmol) . The mixture was stirred at 90 C for 18 h and diluted with water. The aqueous solution was extracted with ethyl acetate. The extract was washed with saturated sodium bicarbonate solution in water, 10% citric acid solution in water and brine, dried over magnesium sulfate, and concentrated under vacuum. The residue was purified by column chromatography eluting with 5% ethyl acetate/n- hexane to afford 11 mg (41 %) the title compound. @H-NMR (CDC13) No.: 0.94-1.00 (6H, m), 1.40-1.51 (4H, m), 1.85-1.95 (lH, m), 1.99 (3H, s), 2 .38 (3H, s), 3.35 (3H, s), 4.08-4.20 (2H, m), 6.94 (lH, d, J = 8.0 Hz), 6.96 (1H, d, J 8.0 Hz), 7.05 (lH, d, J = 8.0 Hz), 7.08 (lH, s), 7.23 (lH, d, J = 8.0 Hz), 7 . 62 (lH, t, J = 8 . 0 Hz). MS Calcd. : 364; Found: 365 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With water; potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; | A mixture containing 0.2 g (0.84 mmol) of 5-bromo-3- methyl-2- (methylthio)pyrimidin-4(3H)-one, 0 .19 g (1.3 mmol) of 2,4-dimethylphenyl boronic acid, 0.35 g (2.5 mmol) of potassium carbonate, 0.15 ml (8.4 mmol) of water, and 0.25g (0.21 mmol) of tetrakis ( triphenylphosphine ) palladium ( 0 ) in 10 ml of dioxane was heated to 90C under a nitrogen atmosphere overnight. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 30 % ethyl acetate/hexanes gave 0.18 g (86%) of product. MS Calcd. : 260; Found: 261 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With cesium fluoride;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 100℃; | A mixture containing 0.5 g (2.3 mmol) of methyl 2- chloro-6-nitrobenzoate, 0.76 g (3.5 mmol) of 2,4- dimethylphenyl boronic acid, 0.7 g (4.6 mmol) of cesium fluoride, and 0.27g (0.23 mmol) of tetrakis(triphenylphosphine)palladium(0) in 10 ml of 1,2- dimethoxyethane was heated to 100C under a nitrogen atmosphere overnight. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 20 % ethyl acetate/hexanes gave 0.312 g (47%) of product. ¹H NMR (CDC13) 5: 2.08 (s, 3H) , 2.35 (s, 3H) , 3. 61 (s, 3H) , 7.01 (s, 2H), 7.07 (s, 1H), 7.54 - 7.62 (m, 2H), 8.16 (d, J 8.1 Hz, 1H) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With water; potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; | A mixture of 5-Bromo-1-(1-propylbutyl)quinolin-4(1H)- one (0.096 g, 0.30 mmol), <strong>[55499-44-0]2,4-dimethylbenzeneboronic acid</strong> (0.067 g, 0.45 mmol), potassium carbonate (0.124 g, 0.89 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.17g, 0.15 mmol) were put under nitrogen gas. Dioxane (4 mL) was added followed by water (27 pL 1.5 mmol). The reaction was heated at 90 C overnight. The solution was cooled and concentrated. Flash chromatography (60% ethyl acetate/hexanes) gave 0.088 g (85% yield) of the desired product. @H NMR (CDC13) 5: 0.85 - 0. 97 (m, 6H) , 1.20 - 1 .40 (m, 4H) , 1.73 - 1.92 (m, 4H), 1.99 (s, 3H), 2.36 (s, 3H), 4.65 - 4.75 (m, 1H), 6.15 (d, J = 8.0 Hz, 1H), 6.95 - 7.03 (m, 3H), 7.30 - 7.40 (m, 1H), 7.47 - 7.59 (m, 3H). MS Calcd. : 347, Found: 348 (M+H),. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With pyridine;copper diacetate; In dichloromethane; at 20℃; for 62h; | A mixture of diethyl 1H-pyrrole-2,3-dicarboxylate (4.21 g, 19.9 mmol), <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (5.98 g, 39.9 mmol) , Cu(OAc)2 (5.43 g, 29.9 mmol) , pyridine (3.22 ml, 39.9 mmol) and dichlormethane (60 ml) was stirred at room temperature for 62 hours. The mixture was diluted with water (100 ml) and extracted with ethyl acetate (100 ml x 2). The extracts were combined, washed with 1N hydrochloric acid and saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo. The residue was perified by silica gel, chromatography eluting with hexane/ethyl acetate (10: 1 - 5: 1) to give 0.98 g (16%) of the title compound. The starting material (3.5 g) was recovered. ¹H NMR (CDC13) No.: 1.08 (3H, t, J = 7.2 Hz), 1.35 (3H, t, J 7.2 Hz), 2.03 (3H, s), 2.36 (3H, s), 4.11 (2H, q, J = 7.2 Hz), 4.32 (2H, q, J = 7.2 Hz), 6.65 (2H, s), 7.00 - 7.15 ( 3H, m) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With cesium fluoride;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 20℃; for 5.25h;Heating / reflux; | To 0.115 g (0.40 mmol) of 1-benzyl-5-chloro-3- methylcinnolin-4 (lH) -one, 0.12 g (0.81 mmol) of cesium fluoride and 0.093 g (0.08 mmol) of tetrakis (triphenylphosphine)palladium (0) was added 4 mL of dimethoxyethane. The dark brown mixture was stirred at room temperature for 15 min. then 0.079 g (0.53 mmol) of <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> was added. This mixture was then heated to reflux for 5 h, cooled to room temperature, diluted with ethyl acetate and filtered through a plug of silica gel. The resulting filtrate was concentrated and the residue was purified by flash chromatography eluting with a 17% ethyl acetate/hexanes mixture to give 0.102 g (71%) of the title compound as a light yellow solid. ¹H NMR (DMSO-d6) No.: 1.96 (s, 3H), 2.32 (s, 3H), 2.38 (s, 3H), 5.60 (s, 2H), 6.93-7.07 (m, 4H), 7.26-7.38 (m, 4H), 7.54 (d, J = 8.2 Hz, 1H) MS Calcd. : 354; Found: 355 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With potassium phosphate;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 90℃; | 5-Choro-4-oxo-1-(1-propylbutyl)-1,4-dihydroquinoline- 3-carbonitrile (0.015g, 0.05 mmol), 2,4- dimethylbenzeneboronic acid (0.012g, 0.079 mmol), and PdCl2(PPh3)2 (0.010g, 0 . 015 mmol) were suspended in toluene (1 mL) . K3P04 (0.074 mL, 0.15 mmol, 2M in water) was added last. The reaction was stirred at 90 C with stirring overnight. The mixture was cooled, filtered through GF/F paper and concentrated. Flash chromatography (40% Ethyl acetate/hexanes) gave the desired product (0.009g, 50%). ¹H NMR (CDC13) 5: 0.929 - 0.981 (m, 6H), 1.23 - 1.37 (m, 4H) , 1.79 - 1.93 (m, 4H) , 1.96 (s, 3H) , 2.37 (s, 3H) , 4.73 - 4.77 (m, 1H), 6.91 (d, J = 8.0 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1H), 7.05 (s, 1H), 7.17 (d, J = 6.8 Hz, 1H), 7.62 - 7.71 (m, 2H), 7.99 (s, 1H). MS Calcd.: 372, Found: 373 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a mixture [OF 2, 4-DIMETHYLPHENYLBORONIC] acid (33 mg, 0.22 [MMOL),] ethyl [{ (1 S)-5-] [ [2-(2-IODO-5-METHYL-1H-IMIDAZOL-4-YL) ETHOXY] -2, 3-DIHYDRO-1H-INDEN-1-YL ACETATE (EXAMPLE] 108,25 mg, 0.06 [MMOL)] and [1,1'-bis [(DIPHENYLPHOSPHINO)-FERROCENE] DICHLOROPALLADIUM (LL),] complex with dichloromethane (1: 1) (5 mg) was added toluene (0.8 mL) and dioxane (0.2 mL). The resulting solution was degassed under argon for half an hour, followed by addition of sodium bicarbonate solution (2 M, 0.2 mL), and then heated up to [85C] for 48 h. The reaction mixture was allowed to cool to rt. The solvent was removed under reduced pressure, and the crude product was carried on for use in the preparation of Example 111 without purification. MS (ES) 433.3 ; HPLC RT 2.69 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100℃; for 1.5h; | STEP 1 2-AMINO-4-CHLORO-6-(2, 4-DIMETHYL-PHENYL)-PYRIMIDINE-5-CARBALDEHYDE Aqueous potassium phosphate was added to a suspension of 2,4- DIMETHYLBENZENE boronic acid and 2-amino-4, 6-DICHLORO-5- pyrimidinecarbaldehyde (3 eq) in 1,4-dioxan, under a nitrogen atmosphere. Dichloro bis (TRIPHENYLPHOSPHINE) PALLADIUM (II) (cat. ) was added and the mixture HEATED,-100C, FOR-90MINS. The resulting mixture was allowed to cool and DICHLOROMETHANE added, the mixture was washed with water and saturated aqueous sodium chloride solution. The solution was dried over anhydrous sodium sulphate and concentrated to a pale yellow solid. The crude solid was purified by column chromatography on silica eluting with mixtures of diethyl ether and hexane. LC retention time 2.354 minutes [M+H] + 262. 0 (Run time 3.75mins) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 70℃; for 18h; | ethyl 2', 4'-dimethylbiphenyl-3-carboxylate (2, 4-Dimethylphenyl) boronic acid (3.0 g, 20.0 mmol), ethyl 3-bromobenzoate (4.3 g, 18.8 mmol) and cesium carbonate (9. 8 g, 30.0 mmol) were added to a mixture of ethanol (20 mL) and toluene (80 mL), and after argon substitution, tetrakis (triphenylphosphine) palladium (0) (0.30 g, 0.26 mmol) was added. The reaction mixture was stirred under an argon atmosphere at 70C for 18 hrs. The reaction mixture was cooled and insoluble material was filtered off through celite. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate: hexane=1 : 10) to give the title compound (5.0 g, yield 100%) as a colorless oil. 1H NMR (CDC13) 8 : 1.39 (3H, t, J=7. 0Hz), 2.23 (3H, s), 2.37 (3H, s), 4.38 (2H, q, J=7. 0Hz), 7.02-7. 54 (5H, m), 8.00-8. 05 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 2h; | Ethanol (8 mL), a 2M aqueous sodium carbonate solution (4 mL), 2,4-dimethylbenzeneboric acid (650 mg, 4.3 mmol) and tetrakistriphenylphosphine palladium complex (456 mg, 0.39 mmol) were added to a solution of 3-amino-4-bromo-6-chloropyridazine (822 mg, 3.9 mmol) in toluene (40 mL), and the mixture was heated at 100C for 2 hours. Water was added thereto, which was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:3) to give the title compound (759 mg, 82%) as a pale brown powder. 1H NMR (400MHz, CDCl3) delta 2.15 (s, 3H), 2.37 (s, 3H), 5.03 (br s, 2H), 7.03 (d, J = 7.7 Hz, 1H), 7.07 (s, 1H), 7.12(d, J = 7.7 Hz, 1H), 7.15 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With trifluoroacetic acid; In diethyl ether; | To fuming nitric acid (1 ml) cooled to -40 C. was added TFA (1 ml). The resulting mixture was allowed to warm slightly to -35 C. and 2,4-dimethyl phenyl boronic acid (150 mg, 1 mmol) was added in one portion. After 1 h, ice was added and the heterogenous mixture was filtered. The resulting solid was suspended in Et2O and extracted with 3N NaOH (aq) (1 ml) then water (2 ml). The aqueous phase was acidified with 3N HCl (aq) (1 ml) and back extracted with EtOAc (3*5 ml). The pooled organics were washed with brine, dried with Na2SO4 decanted and concentrated to give 2,4-dimethyl-5-nitro-phenyl boronic acid (93 mg, 47%). LCMS (ESI+) [M+H]/z Calc'd 196, found 196. 3-Amino-4,6-dimethylphenyl boronic acid was prepared in a similar as that described for Example 40(b), step (i). 1H NMR (CD3OD) delta 6.83 (s, 2H), 6.64 (s, 1H), 2.17 (s, 3H), 2.13 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 130℃; for 0.0833333h;microwave irradiation; | A mixture of 1,6-dichlorophthalazine (300 mg, 1507 mumol), <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (249 mg, 1658 mumol), Pd(PPh3)2Cl2 (52.9 mg, 75.4 mumol, Strem), and sodium carbonate (479 mg, 4522 mumol) in DME:EtOH:H2O=7:2:3 (5 mL) was heated to 130 C. for 5 min in the Emrys Optimizer microwave. The mixture was diluted with MeOH and H2O and concentrated over SiO2. The residue was purified with flash chromatography (MeOH/CH2Cl2=0?2%) to afford the title compound. MS (ESI, pos. ion) m/z: 269 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 85℃; | General procedure to generate biaryl derivatives from toluene-4-sulfonic acid (R)-8-bromo-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester: To a solution of toluene-4-sulfonic acid (R)-8-bromo-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester (1 eq) and substituted benzene boronic acid (1.5 eq) in DME-water (4/1) was added, under N2 atmosphere, tetrakis(triphenylphospine)palladium (0) (0.1 eq) and sodium carbonate (3 eq). The reaction mixture was heated at 85 C. until starting material disappeared. [Reaction monitored by TLC]. After reaction completion the cooled reaction mixture was diluted with water and extracted with ethyl acetate. Combined organic layers were washed with brine, dried (sodium sulfate) and concentrated under vacuum. Chromatography with 10% ethyl acetate in hexanes afforded product as an oil. Using the general procedures outlined above, Intermediates 231-237 were prepared Intermediate 231 Toluene-4-sulfonic acid (R)-8-(2,4-dimethyl-phenyl)-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester: Starting from toluene-4-sulfonic acid (R)-8-bromo-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester (820 mg, 2 mmol) and 2,4-dimethylbenzene boronic acid, 620 mg (73%) was obtained as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene;Heating / reflux; | 3-Chloro-6-(pyridin-2-ylmethoxy)pyridazine (Example 15a) (221 mg, 1 mmol) was dissolved in toluene (10 mL), EtOH (2 mL), and water (1.5 mL). Then <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (150 mg, 1 mmol) was added, followed by K2CO3 (276 mg, 2 mmol) and the mixture was degassed using argon stream. Tetrakis(triphenylphosphine)palladium (232 mg, 0.2 mmol) was added under argon and the mixture was refluxed overnight. The solvents were removed under vacuum and a residual solid was extracted with EtOAc, and successively washed with water and brine dried over MgSO4 filtered and evaporated. The crude material was purified on silica gel (Eluent:50% EtOAc in hexanes) to give 3-(2,4-Dimethylphenyl)-6-(pyridin-2-ylmethoxy)pyridazine (169 mg, 58%) as a white solid. 1H NMR (300 MHz, dMSO): delta 2.26 (s, 3H), 2.32 (s, 3H), 5.62 (s, 2H), 7.13-7.15 (m, 2H), 7.28-7.40 (m, 2H), 7.55-7.56 (d, 1H), 7.78-7.84 (m, 2H), 8.58-8.60 (d, 1H); MS (M+H, 292). The compound had EC50 for activation of umami receptor expressed in an HEK293 cell line of 6.9 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2% | (2-Bromo)-N, N-dipropylimidazo [1, 2-a] pyridin-5-amine (prepared in example 61) (0.17g, 0.57 mmol) was dissolved in 1,2-dimethoxyethane (DME) (1.5 mL). Pd (PPh3) 4 (0. 033g, 0.028 mmol) was added and the reaction stirred at 50 C. for 15 minutes. The solution was cooled and 2,4- dimethylphenylboronic acid (0.103g, 0.69 mmol) in DME (1 mL) was added to the reaction mixture. KOtBu (0.128g, 1.14 mmol) in tBuOH (1 mL) was also added to the reaction. The reaction was heated to 100 C for 1 hr. The solution was filtered through paper and concentrated. Crude material was purified via reverse phase HPLC (acetonitrile containing 0. 1% TFA/water containing 0. 1% TFA) to obtain 3.1 mg of the title compound (2% yield). MS Calcd.: 321; Found: 322 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With pyridine;copper; In N,N-dimethyl-formamide; at 50℃; for 4h; | Stage 1: 3-(Trifluoromethyl)-1-(2,4-dimethylphenyl)-1H-1,2,4-triazole (IV-A-1) A quantity of 1.32 g of <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> and 1.37 g of 3-trifluoromethyl-1,2,4-triazole are heated together with 0.8 g of pyridine and 0.07 g of copper powder in 5 ml of dimethylformamide at 50 C. for 4 hours. Following filtration, the major amount of the DMF is removed by filtration and the product is admixed with dilute 5% strength hydrochloric acid and ethyl acetate. The phases are separated and the organic phase is concentrated on a rotary evaporator. Chromatography (CH2Cl2) gives 1.27 g of (IV-A-1) (59% of theory)logP (HCOOH): 3.19M+: 2411H NMR (CDCl3): 8.3 (s, 1H), 7.13-7.26 (s+2d, 3H), 2.4 (s, 3H), 2.19 (s, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrakis(triphenylphosphine) palladium(0); potassium phosphate monohydrate; In 1,2-dimethoxyethane; at 150℃; under 4500.45 Torr; for 1.5h;Microwave irradiation; | Starting from 2-bromobenzaldehyde (3 mmol, 555 mg, 351 mul) and (2-4-dimethylphenyl)boronic acid (3.9 mmol, 585 mg), under the following conditions (1 h 30 min; 150 C; 6 bar; 300 W), 7h was obtained as a yellow clear oil (412 mg, 65%); IR (KBr) nu (cm-1) 3433 (OH), 2922, 2850, 1695 (CO), 1622, 1597, 1447, 1255, 826, 766; 1H NMR (400 MHz, CDCl3) delta* 9.76 (s, 1H, CHO), 8.01 (d, 1H, Jortho=7.8 Hz, H3), 7.62 (t, 1H, Jortho=7.8 Hz, H5), 7.48 (t, 1H, Jortho=7.8 Hz, H4), 7.29 (d, 1H, Jortho=7.8 Hz, H6), 7.12 (s, 1H, H3'), 7.08 (br s, 2H, H5'&H6'), 2.39 (s, 3H, CH3), 2.07 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) delta* 192.5 (CHO), 145.8 (C1), 138.0 (C4'), 135.9 (C2'), 134.5 (C1'), 133.9 (C2), 133.7 (C5), 130.9 (C6), 130.8 (C3'), 130.2 (C6'), 127.6 (C4), 127.0 (C3), 126.4 (C5'), 21.1 (C4'-CH3), 20.2 (C2'-CH3); LC-MS tR=12.5 min, [ESI+] m/z [M+H]+ 211.*Assignments according to 2D experiments (HMBC, HMQC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;copper diacetate; In dichloromethane; at 20℃;Molecular sieve; | 31A. (S)-2-(1-(4-(2,4-dimethylphenoxy)phenyl)pyrrolidin-2-yl)acetonitrile: A flask was charged with 20B (0.05 g, 0.247 mmol), copper (II) acetate (0.045 g, 0.247 mmol), <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (0.111 g, 0.742 mmol), and powdered 4 molecular sieves to make a thick slurry in dichloromethane (1.236 mL). To this mixture was added triethylamine (0.172 mL, 1.236 mmol) and the mixture became a thick pale blue slurry that was stirred vigorously at ambient temperature in air overnight. The reaction mixture was filtered, and the solids were washed several times with ethyl acetate. The filtrate was concentrated to 0.177 g brown oil. The residue was purified via silica gel chromatography to give 31A (0.0385 g, 0.107 mmol, 43.2% yield). LC-MS Anal. Calc'd for C20H22N2O: 306.17. found [M+H] 307.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 90℃; | General procedure: 4-Amino-7-X-8-(aryl)-N-(alkyl)-cinnoline-3-carboxamide (X = H or F).The corresponding bromide-precursor(III) (1 equiv), the corresponding aryl boronic acid reagent (2.2 equiv), tetrakis(triphenylphosphine)palladium(0) (0.05 equiv) and potassium carbonate (3.0 equiv) in DME/ethanol/water (7/2/3) were heated at 90 C, monitored by LC/MS. The reaction concentration was 0.3 M. Upon completion, the reaction mixture was cooled to room temperature, diluted with chloroform and washed with water. The chloroform layer was dried with magnesium sulfate, and evaporated to constant mass. The crude product was loaded onto a silica gel column, and eluted with 0-10% methanol in methylene chloride to give a yellow or tan solid. The solid was further crystalized from ether/methylene chloride, or purified by HPLC to give a white, yellow or tan solid as the desired product in 50-85% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With palladium diacetate; sodium carbonate; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); In 1,2-dimethoxyethane; water; at 80℃; for 15h;Inert atmosphere; | To a stirred solution of 25 (330 mg, 0.579 mmol) in DME (4 mL) and 2 M aqueous sodium carbonate (0.87 mL, 1.74 mmol) were added <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (173 mg, 1.15 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) (72 mg, 0.116 mmol) and palladium acetate (13 mg, 0.058 mmol) under argon atmosphere. After being stirred at 80 C for 15 h, the reaction mixture was cooled to room temperature. The resulting mixture was filtered through a pad of Celite, and the filtrate was evaporated. The resulting residue was purified by column chromatography on silica gel (hexane/EtOAc, 4:1-1:1) to afford 26a as a brown oil (321 mg, 93%). 1H NMR (300 MHz, CDCl3): delta 7.27 (s, 1H), 7.15-7.00 (m, 6H), 5.65 (m, 1H), 5.46 (m, 1H), 4.43 (m, 1H), 4.30 (m, 1H), 4.17-4.02 (m, 3H), 2.80-2.71 (m, 2H), 2.35 (s, 3H), 2.33-2.22 (m, 2H), 2.23 (s, 3H), 1.86-1.68 (m, 2H), 1.41 (s, 9H), 1.25 (t, J = 7.0 Hz, 3H), 0.79 (s, 9H), -0.13 (s, 3H), -0.24 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; at 90℃; for 6h; | 4-Chloro-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile (65, 75 mg, 0.33 mmol), <strong>[55499-44-0]2,4-dimethylphenylboronic acid</strong> (65 mg, 0.43 mmol), 2 M K3PO4 solution (1 mmol, 0.5 mL) and 1,4-dioxane (3 mL) were charged into a flask and thoroughly degassed. [1,1?-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) (13.5 mg, 0.0167 mmol,) was added and the reaction mixture was heated at 90 C for 6 h. After cooling, the reaction mixture was partitioned between ethyl acetate and brine. The organic layer was separated and the aqueous layer extracted with a further portion of ethyl acetate. The combined ethyl acetate extracts were washed with saturated sodium hydrogen carbonate solution (2 × 30 mL) then brine (2 × 30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (10 g) and the product eluted using 20% ethyl acetate in iso-hexane. The fractions containing product were combined and concentrated in vacuo and the residue further purified by preparative HPLC at pH 4 to afford the title compound 16 (4.3 mg, 4%) as a colourless solid: LC-MS (method A) tR = 2.55 min, m/z = 296 [M+H]+; 1H NMR (400 MHz, CD3OD) delta 2.31 (s, 3H), 2.42 (s, 3H), 2.65 (s, 3H), 7.20 (d, 1H), 7.24 (s, 1H), 7.37 (d, 1H); HRMS, Calcd for C15H14N5S [M+H]+. Found 296.0965 requires 296.0970; HPLC (from method A) 97.3% (tR = 2.51 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In water; N,N-dimethyl-formamide; at 80℃; for 1.5h;Inert atmosphere; | General procedure: DMF (20 mL), 4-chloro-2-methylsulfanyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (46, 2.0 g, 5.64 mmol), NaHCO3 (1 N aq solution, 24.2 mL, 24.2 mmol), and PdCl2(PPh3)2 (280 mg, 0.4 mmol) were added sequentially and the resultant mixture was degassed by bubbling N2 through the mixture for 5 min. The reaction was then heated at 80 C for 1.5 h and the resultant mixture partitioned between EtOAc (250 mL) and brine (250 mL). The organic phase was dried (Na2SO4) and evaporated in vacuo to afford a crude oil. This was purified by flash chromatography on SiO2 (100 g) eluting with hexane to 30% EtOAc/hexane (gradient) to afford the title compound 49 (3.04 g, 98%) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In methanol; water; at 80℃; for 18h;Inert atmosphere; | 2? ,4 ?-dimethyl-[l ,1 ?-biphenyl]-4-carbaldehyde. A mixture of 4-bromobenzaldehyde (3.5 g,0.019 mol), 2,4-dimethylphenyl)boronic acid (3.5 g, 0.023 mol), Na2CO3(2.8 g, 0.026 mol),Pd(dppf)C12 (1 g, 0.0019 mol) in MeCN:H20=1 :1 (50mL) was stirred at 80C under N2 forl 8hrs. The solvent was removed in vacuum and the residue was partitioned between H20 and EtOAc. The organic layer was dried over Na2504, filtered, concentrated and purified by column chromatography (Petroleum ether:EtOAc=1 0:1) to give 2?,4?-dimethyl- [1,1 ?-biphenyl] -4- carbaldehyde (5.5 g, yield 92%) as a yellow solid. |
81% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; | A mixture of <strong>[55499-44-0](2,4-dimethylphenyl)boronic acid</strong> (9.57 mmol), 4- bromobenzaldehyde (9.57 mmol), tetrakis(triphenylphosphine)palladium(0) (0.10 mmol), and potassium carbonate (26 mmol) in water (5 mL) and 1 ,4-dioxane (50 mL) was heated at 80 C overnight. The reaction mixture was filtered and the filtrate was purified by reverse phase HPLC to afford the title product as a solid (81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; at 90℃; | A mixture of 2-(4-bromophenyl)-6-chloro-3-[(35)-l-(cyclopropylcarbonyl)-3- pyrrolidinyl]methyl}-3H-imidazo[4,5-¾]pyridine (0.109 mmol), 2,4- dimethylphenylboronic acid (0.131 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.0109 mmol) in 0.5M aq sodium carbonate (1 mL) and acetonitrile (2 mL) was heated at 90 C overnight. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (0-5% methanol/dichloromethane) gave the title product as a solid (28%). MS(ES)+ m/e 485.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); at 110℃;Schlenk technique; Inert atmosphere; Microwave irradiation; | General procedure: An oven-dried Schlenk tube was flame-dried and backfilled with argon (×3). The tube was then charged with 6-butyl-4-ethoxy-3-iodo-2-methyl-7-(2-phenoxyethoxy)quinoline (100 mg, 0.4 mmol), Pd2(dba)3 (14.5 mg, 0.016 mmol), SPhos (13 mg, 0.032 mmol), boronic acid (97 mg, 0.6 mmol), and anhydrous powdered K3PO4 (168 mg, 0.79 mmol). The Schlenk tube was fitted with a rubber septum and then evacuated and backfilled with argon (this process was repeated three times). [0133] Dry solvent (Toluene, DMF, or 2-butanol, 3 mL) was added through the septum via syringe and the resulting solution was stirred for 1 min. while purging with argon before replacing the rubber septum with the Teflon screwcap. The reaction was set to the oil bath until completion was observed via HPLC analysis. The reaction was cooled to room temperature and then diluted with 20 mL chloroform and 20 mL of methanol. This mixture was brought to a boil with a heat gun and then filtered over a pad of celite. The eluent was concentrated under reduced pressure and the residual oil was purified further via flash chromatography. Following general procedure F, as given in Example 7, the title compound was prepared in 64% yield. This reaction was performed in a microwave reactor at a temperature of 110 C. 1H NMR (400 MHz, DMSO) delta 11.56 (s, 1H), 7.81 (s, 1H), 7.35-7.27 (m, 3H), 7.22 (d, J=8.3 Hz, 1H), 7.05-6.93 (m, 5H), 4.38 (d, J=5.9 Hz, 4H), 2.60 (t, J=7.3 Hz, 2H), 2.03 (s, 6H), 1.52 (dd, J=14.8, 7.6 Hz, 2H), 1.27-1.21 (m, 2H), 0.82 (t, J=7.3 Hz, 3H). 13C NMR (101 MHz, DMSO) delta 173.96, 159.21, 158.41, 145.82, 140.19, 139.59, 135.53, 132.69, 131.32, 129.49, 129.09, 127.61, 125.75, 125.34, 120.78, 118.81, 118.12, 114.53, 97.98, 66.86, 66.07, 31.46, 29.28, 21.88, 19.18, 18.29, 13.74. HRMS (ESI) calculated for C30H33NO3 [M+H]+: 456.2533. found 456.2541. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With caesium carbonate; at 70℃; for 9h; | General procedure: A mixture of the appropriate arylboronic acid (1.0 mmol),NH2CHO (2.5 mmol), base (1.3 mmol) and rGO/Cu NPs (25 mg) wasstirred at 70C for the appropriate time. After completion of reac-tion (as monitored by TLC), ethyl acetate and water was added andorganic layer was separated. Then, aqueous layer was extracted with ethyl acetate, washed with water, dried over MgSO4, filteredand evaporated under reduced pressure. The residue was purifiedby column chromatography to give the desired pure products. Allproducts are known in the literature and were characterized by IR,NMR and melting points and their spectroscopic data identical tothat reported in the literature [15,16]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate; ammonium hydroxide; In methanol; at 60℃; for 14h; | General procedure: RGO/Cu NPs (25 mg), arylboronic acid (1.0 mmol), K2CO3(1.3 mmol), 25-28% aqueous ammonia (5 mmol) and methanol(4 mL) were added to a 50 mL round-bottomed flask. The reactionmixture was stirred under reflux conditions for the appropriatetime. After completion of the reaction as monitored by TLC, themixture was filtered, and the solvent of the filtrate was removedunder vacuum with the aid of a rotary evaporator. The residue waspurified by column chromatography on silica gel to afford the prod-uct. All products are known in the literature and the physical data(mp, IR, NMR) of the products were found to be identical with thosereported in the literature [36,37]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere; | Step 4: [5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-1,2-thiazol-4-yl]methanol Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed [5-bromo-3-(trifluoromethyl)-1,2-thiazol-4-yl]methanol (100 mg, 0.38 mmol, 1.00 equiv), dioxane (3 mL), <strong>[55499-44-0](2,4-dimethylphenyl)boronic acid</strong> (113 mg, 0.75 mmol, 1.97 equiv), Pd(PPh3)4 (44 mg, 0.04 mmol, 0.10 equiv), K3PO4 (402 mg, 1.89 mmol, 4.96 equiv). The resulting solution was stirred for 3 h at 90 C. in an oil bath. The solvent was removed and the residue was applied onto a TLC plate with ethyl acetate/petroleum ether (1:3). This resulted in 100 mg (crude) of [5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-1,2-thiazol-4-yl]methanol as yellow oil. | |
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere; | Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed [5-bromo-3-(trifluoromethyl)-1,2-thiazol-4-yl]methanol (100 mg, 0.38 mmol, 1.00 equiv), dioxane (3 mL), <strong>[55499-44-0](2,4-dimethylphenyl)boronic acid</strong> (113 mg, 0.75 mmol, 1.97 equiv), Pd(PPh3)4 (44 mg, 0.04 mmol, 0.10 equiv), K3PO4 (402 mg, 1.89 mmol, 4.96 equiv). The resulting solution was stirred for 3 h at 90 C. in an oil bath. The solvent was removed and the residue was applied onto a TLC plate with ethyl acetate/petroleum ether (1:3). This resulted in 100 mg (crude) of [5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-1,2-thiazol-4-yl]methanol as yellow oil. | |
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere; | Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed [5-bromo-3-(trifluoromethyl)-l,2-thiazol-4- yl]methanol (100 mg, 0.38 mmol, 1.00 equiv), dioxane (3 mL), (2,4- dimethylphenyl)boronic acid (113 mg, 0.75 mmol, 1.97 equiv), Pd(PPh3)4 (44 mg, 0.04 mmol, 0.10 equiv), K3PO4 (402 mg, 1.89 mmol, 4.96 equiv). The resulting solution was stirred for 3 h at 90C in an oil bath. The solvent was removed and the residue was applied onto a TLC plate with ethyl acetate/petroleum ether (1 :3). This resulted in 100 mg (crude) of [5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-l,2-thiazol-4-yl]methanol as yellow oil. |
Tags: 55499-44-0 synthesis path| 55499-44-0 SDS| 55499-44-0 COA| 55499-44-0 purity| 55499-44-0 application| 55499-44-0 NMR| 55499-44-0 COA| 55499-44-0 structure
[ 55499-43-9 ]
3,4-Dimethylphenylboronic acid
Similarity: 0.95
[ 55499-43-9 ]
3,4-Dimethylphenylboronic acid
Similarity: 0.95
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P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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 |
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