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CAS No. : | 854373-97-0 | MDL No. : | MFCD06201036 |
Formula : | C7H10BNO3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FXUMKSCYKPOZOO-UHFFFAOYSA-N |
M.W : | 166.97 | Pubchem ID : | 11309733 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.29 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 45.36 |
TPSA : | 62.58 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) : | -7.01 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 0.43 |
Log Po/w (WLOGP) : | -0.84 |
Log Po/w (MLOGP) : | -0.84 |
Log Po/w (SILICOS-IT) : | -0.92 |
Consensus Log Po/w : | -0.43 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.32 |
Solubility : | 8.03 mg/ml ; 0.0481 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.31 |
Solubility : | 8.15 mg/ml ; 0.0488 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.44 |
Solubility : | 6.05 mg/ml ; 0.0362 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.32 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | 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 |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 5h;Inert atmosphere of nitrogen; | The mixture of 9-bromo-2-methoxy-7-methylimidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine (100 mg, 0.340 mmol), various boronic acids (commercially available from Sigma-Aldrich Co., Boron Molecular Inc., Combi-Blocks Inc., or SynQuest Laboratories, USA), potassium carbonate (141 mg, 1.020 mmol), and tetrakis(triphenylphosphine) palladium(0) (19.65 mg, 0.017 mmol) in a 20 mL vial was vacuumed and refilled with nitrogen. Dioxane (6.9 mL) and water (2.3 mL) were added to the reaction. The final mixture was stirred at 90 C. for 5 h. The reaction was cooled to RT. Solvent was evaporated in Genevac and the residue was purified by column chromatography using 50% ethyl acetate in dichloromethane followed by 10% methanol in dichloromethane as eluent to provide the final products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; acetone; at 85℃; for 16h; | Synthesis of Isopropyl 4-(3-(2-ethoxypyridin-3-yl)pyrazolo[l,5-a]pyrimidin-5- yl)piperazine-l-carboxylate To a 1 liter round bottom flask was added 15.00 g (40.76 mmol) of isopropyl 4-(3- bromopyrazolo[l,5-a]pyrimidin-5-yl)piperazine-l-carboxylate, 8.85 g (52.99 mmol) of (2- ethoxypyridin-3-yl)boronic acid, 14.06 g (101.90 mmol) of K2CO3, 1.41g (1.22 mmol) of P(PPh3)4, and a stirring rod. After adding all the solids, 200 ml of MeCN was added, followed by the addition of 100 mL of water. The reaction flask was plunged into an oil bath pre-heated to 85C, and stirred vigorously. This reaction was setup to reflux. After stirring at 85C for about 16 hr, it was allowed to cool to RT and diluted with 200 mL of EtOAc. The organic layer was separated, and the aqueous layer was extracted twice with 80 mL portions of EtOAc. The combined organic layers was washed with brine, dried over MgS04, and concentrated. A small volume of DCM was used to dissolve the crude mixture, and then loaded directly onto a 750 g silica gel column for separation on the ISCO-XL. A gradient of 50% EtOAc/hex to 100% EtOAc was run for the first 35 minutes. The desired product did not elute, only some impurities eluted. However, about 10 minutes into running with 100% EtOAc, the desbromo side product starts el uting together with the desired product. Even though the desbromo compound is spread through all the fractions containing the desired product, the percentage of the desbromo compound seem to decrease with time. Therefore, the initial fractions containing the highest percentages of the desbromo were discarded, and the remaining fractions were concentrated to obtain 13.46 g of about 86% purity at 254 nm. (with about 14% desbromo compound). This material was recrystallized twice, using IPAC and heptanes, to obtain 11.4 g (68%) of the desired product. ^ NMR (400 MHz, CHLOROFORM-d) delta ppm 1.30 (d, J=6.32 Hz, 6 H) 1.53 (t, J=7.07 Hz, 3 H) 3.59 - 3.70 (m, 4 H) 3.70 - 3.81 (m, 4 H) 4.53 (q, J=7.07 Hz, 2 H) 5.00 (dt, J=12.44, 6.28 Hz, 1 H) 6.38 (d, J=7.83 Hz, 1 H) 6.98 (dd, J=7.45, 4.93 Hz, 1 H) 8.01 (dd, J=4.93, 1.89 Hz, 1 H) 8.37 (d, J=7.83 Hz, 1 H) 8.70 (s, 1 H) 8.76 (dd, J=7.45, 1.89 Hz, 1 H). LRMS (ESI) m/e 411 [(M + H)+, calcd for C21H26N6O3 410]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | Example 66A N-alpha-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(2-ethoxypyridin-3-yl)-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide (0630) (0631) 100 mg (0.16 mmol) of 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}-cyclohexyl)carbonyl]-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide and 18 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 1.4 ml of 1,2-dimethoxyethane under argon and stirred at RT for 10 min. A solution of 80 mg (0.48 mmol) of <strong>[854373-97-0]2-ethoxypyridine-3-boronic acid</strong> in 0.5 ml of ethanol was added dropwise to the reaction mixture and stirred at RT for a further 10 min. After the addition of 1.2 ml of 2N aqueous sodium carbonate solution, the mixture was stirred at RT for 5 min and under reflux for 3 h. 0.5N aqueous hydrochloric acid solution was added to the reaction mixture, the phases were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulphate, and the solvent was removed on a rotary evaporator. The residue was dissolved in a little methanol, filtered through a Millipore syringe filter and separated by preparative HPLC (mobile phase: acetonitrile/water gradient). The product-containing fractions were concentrated and the residue was stirred with a little acetonitrile. This gave 31 mg (28% of theory) of the title compound. (0632) LC-MS (Method 1): Rt=1.11 min; MS (ESIneg): m/z=667 [M-H]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 85℃; for 18h; | A solution of methyl 4-bromo-1-(4-(3,4-dichlorophenyl)-5-(isopropylthio)thiazol-2- yl)-3-methyl-1H-pyrazole-5-carboxylate (50 mg, 0.096 mmol), <strong>[854373-97-0]2-ethoxypyridin-3-ylboronic acid</strong> (19 mg, 0.12 mmol), Pd(PPh3)4 (11 mg, 0.10 mmol), Na2CO3 (51 mg, 0.48 mmol) in degassed 1,4-dioxane and H2O (4:1, 1.9 mL) was heated at 85 C for 18 hours. Water (5 mL) was added and the mixture was extracted with EtOAc (3x5 mL). The combined organic layers were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (5 to 10%) and afforded the title compound (26 mg, 0.048 mmol, 50%) as a colorless oil. |
50% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 85℃; for 18h; | A solution of methyl 4-bromo-1-(4-(3,4-dichlorophenyl)-5-(isopropylthio)thiazol-2- yl)-3-methyl- 1 H-pyrazole-5-carboxylate (50 mg, 0.096 mmol), <strong>[854373-97-0]2-ethoxypyridin-3-ylboronic acid</strong> (19 mg, 0.12 mmol), Pd(PPh3)4 (11 mg, 0.10 mmol), Na2003 (51 mg, 0.48 mmol) in degassed 1,4-dioxane and H20 (4:1, 1.9 mL) was heated at85 C for 18 hours. Water (5 mL) was added and the mixture was extracted with EtOAc (3x5 mL). The combined organic layers were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel using a solution of EtOAc in hexanes (5 to 10%) and afforded the title compound (26 mg, 0.048 mmol, 50%) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation; | A mixture of 6-chloro-3-isopropyl-1-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazolo[3,4-b]pyridin-4-amine (65 mg, 0.20 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (68 mg, 0.41 mol), Pd(dppf)Cl2 (38 mg, 0.05 mmol), Cs2CO3 (167 mg, 0.5 mmol) in dioxane (3 mL) and water (1 mL) was degassed and purged with nitrogen 3 times, and then the mixture was stirred at 100 C. for 1 hour under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (45 mL*3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by preparative HPLC to give 6-(2-ethoxypyridin-3-yl)-3-isopropyl-1-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazolo[3,4-b]pyridin-4-amine (41 mg). 1H NMR (CDCl3 400 MHz): delta 8.32 (dd, J=2.0, 7.6 Hz, 1H), 8.20 (dd, J=2.0, 4.8 Hz, 1H), 7.55 (s, 1H), 7.42 (s, 1H), 7.05-7.01 (m, 2H), 4.96 (brs, 1H), 4.48 (q, J=7.2 Hz, 2H), 4.43 (d, J=4.8 Hz, 2H), 4.06 (s, 3H), 3.89 (s, 3H), 3.26-3.19 (m, 1H), 1.43 (d, J=6.8 Hz 6H), 1.41-1.38 (m, 3H). LC-MS: tR=1.971 minutes (Method C), m/z=406.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; at 80℃; for 2h;Inert atmosphere; | To a solution of 2-((2-chloro-5-isopropyl-7-methylimidazo[1,5-b]pyridazin-4-yl)amino)acetonitrile (50 mg, 0.19 mmol) in dioxane (2 mL) was added <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (47 mg, 0.28 mmol), Cs2CO3 (124 mg, 0.38 mmol) and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (12 mg, 0.02 mol). The mixture was degassed with N2 and heated at 80 C. for 2 hours. The mixture was cooled to 20 C. and extracted with ethyl acetate (20 mL*2). The combined organic phases were washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated to give the crude product. The residue was purified by flash chromatography on silica gel (10%?50% ethyl acetate in petroleum ether) to give 2-((2-(2-ethoxypyridin-3-yl)-5-isopropyl-7-methylimidazo[1,5-b]pyridazin-4-yl)amino)acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
290 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation; | Intermediate: 2-(2-ethoxypyridin-3-yl)-5-isopropyl-N-(4-methoxybenzyl)-7-methylimidazo[1,5-b]pyridazin-4-amine To a solution of 2-chloro-5-isopropyl-N-[(4-methoxyphenyl)methyl]-7-methyl-imidazo[1,5-b]pyridazin-4-amine (250 mg, 0.72 mmol) in dioxane (4 mL) and water (2 mL) was added <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (182 mg, 1.09 mmol), Cs2CO3 (472 mg, 1.45 mmol) and Pd(dppf)Cl2 (53 mg, 0.07 mmol). The mixture was degassed with nitrogen and heated under microwave irradiation at 100 C. for 1 hour. The mixture was cooled to room temperature and extracted with ethyl acetate (20 mL*2). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated to give the crude product. The residue was purified by flash chromatography on silica gel (10% to 50% ethyl acetate in petroleum ether) to give 2-(2-ethoxypyridin-3-yl)-5-isopropyl-N-(4-methoxybenzyl)-7-methylimidazo[1,5-b]pyridazin-4-amine (290 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
424 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation; | A mixture of 6-chloro-3-isopropyl-N-[(4-methoxyphenyl)methyl]-1-methyl-pyrazolo[3,4-b]pyridin-4-amine (424 mg, 1 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (410 mg, 2 mmol), Pd(dppf)Cl2 (225 mg, 0.3 mmol), Cs2CO3 (1 g, 3 mmol) in dioxane (3 mL) and water (1 mL) was degassed and purged with nitrogen 3 times, and then the mixture was stirred at 100 C. for 1 hour under microwave irradiation. Water (50 mL) was added and the mixture was extracted with ethyl acetate (60 mL*3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by flash chromatography with petroleum ether:ethyl acetate=3:1 to 2:1 to give 6-(2-ethoxy-3-pyridyl)-3-isopropyl-N-[(4-methoxyphenyl)methyl]-1-methyl-pyrazolo[3,4-b]pyridin-4-amine (500 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 5-chloro-1 -isopropyl-N-(4-methoxybenzyl)-3-methyl-1 /- -pyrazolo[4,3- b]pyridin-7-amine (60 mg, 174 muetaiotaomicronIota) in dioxane (2 mL) and H20 (0.5 mL) was added Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)CI2(25 mg, 35 muetaiotaomicronIota) and Cs2C03(141 .72 mg, 435 muetaiotaomicronIota) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (52 mg, 313 muetaiotaomicronIota). The mixture was stirred at 100C for 1 hour under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mLchi3). The combined organic layers were washed with brine ( 20 mL), dried over Na2S04and concentrated. The crude mixture was purified by flash chromatography with petroleum ether:ethyl acetate = 1 :1 to 0:1 to give 5-(2- ethoxypyridin-3-yl)-1 -isopropyl-N-(4-methoxybenzyl)-3-methyl-1 H-pyrazolo[4,3-b]pyridin-7- amine (50 mg, 67% yield).1H NMR (chloroform-c/400 MHz) delta 8.27-8.25 (m, 1 H), 8.17-8.16 (m, 1 H), 7.32 (d, J = 8.8 Hz, 2H), 7.22 (s, 1 H), 7.03-7.00 (m, 1 H), 6.95 (d, J = 8.4 Hz, 2H), 4.81 -4.76 (m, 1 H), 4.65 (brs, 1 H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1 .60 (d, J = 6.4 Hz, 6H), 1 .36 (t, J = 7.2 Hz, 3H). |
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 5-chloro-l-isopropyl-/V-(4-methoxybenzyl)-3-methyl-l/-/-pyrazolo[4,3-b]pyridin-7- amine (60 mg, 174 pmol) in dioxane (2 mL) and H2O (0.5 mL) was added Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (25 mg, 35 pmol) and CS2CO3 (141.72 mg, 435 pmol) and (2- ethoxypyridin-3-yl)boronic acid (52 mg, 313 pmol). The mixture was stirred at 100C for 1 hour under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine ( 20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by flash chromatography with petroleum ethenethyl acetate = 1:1 to 0:1 to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-/V-(4-methoxybenzyl)-3- methyl-l/-/-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 67% yield). 1H NMR (chloroform-d 400 MHz) d 8.27-8.25 (m, 1H), 8.17-8.16 (m, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.22 (s, 1H), 7.03-7.00 (m, 1H), 6.95 (d, J = 8.4 Hz, 2H), 4.81-4.76 (m, 1H), 4.65 (brs, 1H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1.60 (d , J = 6.4 Hz, 6H), 1.36 (t, J = 7.2 Hz, 3H). |
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 132 5-chloro-1-isopropyl-N-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine (60 mg, 174 mumop in 134 dioxane (2 mL) and 97 H2O (0.5 mL) was added 135 Pd(1,1?-bis(diphenylphosphino)ferrocene)Cl2 (25 mg, 35 mumop and 101 Cs2CO3 (141.72 mg, 435 mumol) and 136 <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (52 mg, 313 mumol). The mixture was stirred at 100 C. for 1 hour under microwave irradiation. 46 Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by flash chromatography with petroleum ether:ethyl acetate=1:1 to 0:1 to give 137 5-(2-ethoxypyridin-3-yl)-1-isopropyl-N-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 67% yield). 1H NMR (chloroform-d 400 MHz) delta 8.27-8.25 (m, 1H), 8.17-8.16 (m, 1H), 7.32 (d, J=8.8 Hz, 2H), 7.22 (s, 1H), 7.03-7.00 (m, 1H), 6.95 (d, J=8.4 Hz, 2H), 4.81-4.76 (m, 1H), 4.65 (brs, 1H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1.60 (d, J=6.4 Hz, 6H), 1.36 (t, J=7.2 Hz, 3H). |
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 134 5-chloro-1-isopropyl-N-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine (60 mg, 174 mumol) in 136 dioxane (2 mL) and 99 H2O (0.5 mL) was added 137 Pd(1,1?-bis(diphenylphosphino)ferrocene)Cl2 (25 mg, 35 mumol) and 103 Cs2CO3 (141.72 mg, 435 mumol) and 138 <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (52 mg, 313 umol). The mixture was stirred at 100 C. for 1 hour under microwave irradiation. 55 Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by flash chromatography with petroleum ether:ethyl acetate=1:1 to 0:1 to give 139 5-(2-ethoxypyridin-3-yl)-1-isopropyl-N-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 67% yield). 1H NMR (chloroform-d 400 MHz) delta 8.27-8.25 (m, 1H), 8.17-8.16 (m, 1H), 7.32 (d, J=8.8 Hz, 2H), 7.22 (s, 1H), 7.03-7.00 (m, 1H), 6.95 (d, J=8.4 Hz, 2H), 4.81-4.76 (m, 1H), 4.65 (brs, 1H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1.60 (d, J=6.4 Hz, 6H), 1.36 (t, J=7.2 Hz, 3H). |
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 5-chloro-l-isopropyl-/V-(4-methoxybenzyl)-3-methyl-l/-/-pyrazolo[4,3-b]pyridin-7- amine (60 mg, 174 pmol) in dioxane (2 mL) and H2O (0.5 mL) was added Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (25 mg, 35 pmol) and CS2CO3 (141.72 mg, 435 pmol) and (2- ethoxypyridin-3-yl)boronic acid (52 mg, 313 pmol). The mixture was stirred at 100C for 1 hour under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine ( 20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by flash chromatography with petroleum ethenethyl acetate = 1:1 to 0:1 to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-/V-(4-methoxybenzyl)-3- methyl-l/-/-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 67% yield). 1H NMR (chloroform-d 400 MHz) d (0834) 8.27-8.25 (m, 1H), 8.17-8.16 (m, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.22 (s, 1H), 7.03-7.00 (m, 1H), 6.95 (d, J = 8.4 Hz, 2H), 4.81-4.76 (m, 1H), 4.65 (brs, 1H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1.60 (d , J = 6.4 Hz, 6H), 1.36 (t, J = 7.2 Hz, 3H). |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Microwave irradiation; | To a solution of 5-chloro-l-isopropyl-/V-(4-methoxybenzyl)-3-methyl-l/-/-pyrazolo[4,3- £>]pyridin-7-amine (60 mg, 174 mitioI) in dioxane (2 mL) and H20 (0.5 mL) was added Pd(l,l'-bis(diphenylphosphino)ferrocene)Cl2 (25 mg, 35 pmol) and CS2CO3 (141.72 mg, 435 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (52 mg, 313 pmol). The mixture was stirred at 100C for 1 hour under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL x 3). The combined organic layers were washed with brine ( 20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by flash chromatography with petroleum ethenethyl acetate = 1:1 to 0:1 to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.55 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; | A mixture of 5-bromo-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.56 g, 1 .98 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (497 mg, 2.98 mmol), Pd(dppf)CI2(145 mg, 0.2 mmol), Cs2C03(1 .94 g, 5.95 mmol) in dioxane (8 mL), water (2 mL) was stirred at 100C for 2 hours. The mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 mL chi 2). The combined organic layers were washed with brine (20 mL), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10:1 to 3:1 ) to give 5-(2-ethoxypyridin-3-yl)-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3- b]pyridine-7-carbaldehyde (0.55 g). |
0.55 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; | A mixture of 5-bromo-1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.56 g, 1.98 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (497 mg, 2.98 mmol), Pd(dppf)C12 (145 mg, 0.2 mmol), Cs2CO3 (1.94 g, 5.95 mmol) in dioxane (8 mL), water (2 mL) was stirred at 100C for 2 hours. Themixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10:1 to 3:1) to give 5-(2-ethoxypyridin-3-yl)- 1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.55 g). |
0.55 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; | A mixture of 5-bromo-1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.56 g, 1.98 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (497 mg, 2.98 mmol), Pd(dppf)Cl2 (145 mg, 0.2 mmol), Cs2CO3 (1.94 g, 5.95 mmol) in dioxane (8 mL), water (2 mL) was stirred at 100 C. for 2 hours. The mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 mL*2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10:1 to 3:1) to give 5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.55 g). |
0.55 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; | A mixture of 335 5-bromo-1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.56 g, 1.98 mmol), 138 <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (497 mg, 2.98 mmol), Pd(dppf)Cl2 (145 mg, 0.2 mmol), 103 Cs2CO3 (1.94 g, 5.95 mmol) in 136 dioxane (8 mL), 55 water (2 mL) was stirred at 100 C. for 2 hours. The mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 mL×2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10:1 to 3:1) to give 344 5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-1H-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.55 g). |
0.55 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; | A mixture of 5-bromo-l-isopropyl-3-methyl-l/-/-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.56 g, 1.98 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (497 mg, 2.98 mmol), Pd(dppf)Cl2 (145 mg, 0.2 mmol), CS2CO3 (1.94 g, 5.95 mmol) in dioxane (8 mL), water (2 mL) was stirred at 100C for 2 hours. The mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (S1O2, Petroleum ether/Ethyl acetate = 10:1 to 3:1) to give 5-(2-ethoxypyridin-3-yl)- l-isopropyl-3-methyl-l/-/-pyrazolo[4,3-b]pyridine-7-carbaldehyde (0.55 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.16 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | A mixture of N-[(5-bromo-1-isopropyl-3-methylpyrazolo[4,3-b]pyridin-7-yl)methyl]-5-methoxypyridin-3-amine (69 mg, 0.18 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (59 mg, 0.35 mmol), Pd(dppf)CI2(26 mg, 0.03 mmol), Cs2C03(1 15 mg, 0.35 mmol) in dioxane (3 mL) and water (1 mL) was degassed and purged with N2 3 times, and then the mixture was stirred at 100C for 2 hours under a N2atmosphere. Water (20 mL) was added and the mixture was extracted with ethyl acetate (30 mL chi 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give N-[[5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methylpyrazolo[4,3-b]pyridin-7-yl]methyl]-5-methoxypyridin-3-amine (48.16 mg). |
48.16 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | A mixture of /V-[(5-bromo-l-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-yl)methyl]-5-methoxy- pyridin-3-amine (69 mg, 0.18 mmol), <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (59 mg, 0.35 mmol), Pd(dppf)Cl2 (26 mg, 0.03 mmol), CS2CO3 (115 mg, 0.35 mmol) in dioxane (3 mL) and water (1 mL) was degassed and purged with N2 3 times, and then the mixture was stirred at 100C for 2 hours under a N2 atmosphere. Water (20 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative HPLC to give //-[[5-(2-ethoxy-3-pyridyl)- l-isopropyl-3-methyl -pyrazolo[4,3-b]pyridin-7-yl]methyl]-5-methoxy-pyridin-3-amine (48.16 mg). XH NMR (Cloroform-d, 400 MHz): 2H), 4.40 (q, J = 7.2 Hz, 2H), 4.18-4.16 (m, 1H), 3.83 (s, 3H), 2.72 (s, 3H), 1.58 (d, J = 7.2 Hz, 6HJ.1.27 (t, J = 7.2 Hz, 3H). LC-MS (m/z) 433.1 (MH+); tR = 1.88 (Method A). |
48.16 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | A mixture of 337 N-[(5-bromo-1-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-yl)methyl]-5-methoxy-pyridin-3-amine (69 mg, 0.18 mmol), 138 <strong>[854373-97-0](2-ethoxy-3-pyridyl)boronic acid</strong> (59 mg, 0.35 mmol), Pd(dppf)Cl2 (26 mg, 0.03 mmol), 103 Cs2CO3 (115 mg, 0.35 mmol) in 136 dioxane (3 mL) and 55 water (1 mL) was degassed and purged with N2 3 times, and then the mixture was stirred at 100 C. for 2 hours under a N2 atmosphere. Water (20 mL) was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by preparative HPLC to give 1208 N-[[5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl -pyrazolo[4,3-b]pyridin-7-yl]methyl]-5-methoxy-pyridin-3-amine (48.16 mg). (1389) 1H NMR (Cloroform-d, 400 MHz): delta 8.27 (dd, J=2.0, 7.6 Hz, 1H), 8.18 (dd, J=2.0, 4.8 Hz, 1H), 8.00 (s, 1H), 7.81-7.80 (m, 2H), 7.05-7.02 (m, 1H), 6.49-6.48 (m, 1H), 4.90-4.87 (m, 1H), 4.74 (d, J=5.6 Hz, 2H), 4.40 (q, J=7.2 Hz, 2H), 4.18-4.16 (m, 1H), 3.83 (s, 3H), 2.72 (s, 3H), 1.58 (d, J=7.2 Hz, 6H).1.27 (t, J=7.2 Hz, 3H). LC-MS (m/z) 433.1 (MH+); tR=1.88 (Method A). |
48.16 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | Pd(dppf)Cl2 (26 mg, 0.03 mmol), CS2CO3 (115 mg, 0.35 mmol) in dioxane (3 mL) and water (1 mL) was degassed and purged with N2 3 times, and then the mixture was stirred at 100C for 2 hours under a N2 atmosphere. Water (20 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and (1749) concentrated. The crude mixture was purified by preparative HPLC to give //-[[5-(2-ethoxy-3-pyridyl)- l-isopropyl-3-methyl -pyrazolo[4,3-b]pyridin-7-yl]methyl]-5-methoxy-pyridin-3-amine (48.16 mg). (1750) XH NMR (Cloroform-d, 400 MHz): (1751) 2H), 4.40 (q, J = 7.2 Hz, 2H), 4.18-4.16 (m, 1H), 3.83 (s, 3H), 2.72 (s, 3H), 1.58 (d, J = 7.2 Hz, 6HJ.1.27 (t, J = 7.2 Hz, 3H). LC-MS (m/z) 433.1 (MH+); tR = 1.88 (Method A). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B). |
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.55h;Inert atmosphere; Microwave irradiation; | To a solution of 408 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 mumop and 136 <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in 134 dioxane (2 mL) and 97 H2O (0.7 mL) was added 101 Cs2CO3 (57 mg, 175 mumol) and 135 Pd(1,1?-bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 mumol). The mixture was purged with nitrogen for 3 minutes then stirred at 100 C. for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane:methanol=20:1 twice, and then the crude product was further purified by preparative HPLC to give 409 5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J=1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J=6.4 Hz, 6H), 1.43 (t, J=6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR=2.08 minutes (Method B). |
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Microwave irradiation; | To a solution of 804 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 mumop and 138 <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in 136 dioxane (2 mL) and 99 H2O (0.7 mL) was added 103 Cs2CO3 (57 mg, 175 mumol) and 137 Pd(1,1?-bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 umol). The mixture was purged with nitrogen for 3 minutes then stirred at 100 C. for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane:methanol=20:1 twice, and then the crude product was further purified by preparative HPLC to give 805 5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). (0924) 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J=1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J=6.4 Hz, 6H), 1.43 (t, J=6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR=2.08 minutes (Method B). |
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Microwave irradiation; | To a solution of 5,7-dichloro-l-isopropyl-3-methyl-l/-/-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 mL) was added CsF (187 mg, 1.23 mmol, 45 pL) and (5-methyl-l,3,4-oxadiazol-2- yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-l-isopropyl-3-methyl-/V-((5-methyl- l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (50 mg). To a solution of 5-chloro-l-isopropyl-3-methyl-/V-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). (1165) XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B). | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.55h;Inert atmosphere; Microwave irradiation; | General procedure: To a solution of 5-chloro-l-isopropyl-3-methyl-//-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B). |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.55h;Inert atmosphere; Microwave irradiation; | General procedure: To a solution of 5-chloro-l-isopropyl-3-methyl-//-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Microwave irradiation; | General procedure: To a solution of 5,7-dichloro-1 -isopropyl-3-methyl-1 H-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 ml_) was added CsF (187 mg, 1 .23 mmol, 45 muIota_) and (5-methyl-1 ,3,4- oxadiazol-2-yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h; | A solution of 5-bromo-l,3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4,3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h; | A solution of 5-bromo-l,3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4,3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h; | A solution of 5-bromo-l,3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4,3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h; | A solution of 5-bromo-l,3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4,3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h; | A solution of 5-bromo-l,3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4,3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.1 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.55h;Inert atmosphere; Microwave irradiation; | To a solution of 5-chloro-l-isopropyl-3-methyl-//-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a solution of 5,7-dichloro-l-isopropyl-3-methyl-l/-/-pyrazolo[4,3-b]pyridine (100 mg, 0.41 mmol) in NMP (2 mL) was added CsF (187 mg, 1.23 mmol, 45 pL) and (5-methyl-l,3,4-oxadiazol-2- yl)methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100C for 18 hours. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-l-isopropyl-3-methyl-/V-((5-methyl- l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (50 mg). To a solution of 5-chloro-l-isopropyl-3-methyl-/V-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and <strong>[854373-97-0](2-ethoxypyridin-3-yl)boronic acid</strong> (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; | Step 3-4, Preparation of tert-butyl (3R)-4-[4-(2-ethoxypyridin-3-yl)-3-fluoro-2-(methoxycarbonyl)phenyl]-3-ethylpiperazine-1-carboxylate To a mixture of tert-butyl (3R)-4-[4-bromo-3-fluoro-2-(methoxycarbonyl)phenyl]-3-ethylpiperazine-1-carboxylate (267 mg, 0.600 mmol), (2-ethoxypyridin-3-yl)boronic acid (150 mg, 0.900 mmol), Pd[t-Bu2P(4-NMe2C6H4)]2Cl2) (42.5 mg, 0.0600 mmol), and K2CO3 (249 mg, 1.80 mmol) in a sealed tube was added dioxane (4 mL) and H2O (0.4 mL). The resulting solution was degassed with N2 (g) for 10 min, sealed, and stirred at 100 C. for 30 min. The reaction was treated with additional (2-ethoxypyridin-3-yl)boronic acid (37.8 mg, 0.226 mmol), Pd[t-Bu2P(4-NMe2C6H4)]2Cl2) (13.4 mg, 0.0189 mmol), and K2CO3 (78.3 mg, 0.567 mmol) and stirred at 100 C. for additional 30 min. The mixture was concentrated and purified by C18 reversed phase column chromatography to give the title compound (255 mg, 87% yield) as a brown gum. LCMS (M+H)+: 488.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate; | Step 11-2, Preparation of methyl 3-[(2R)-4-[(tert-butoxy)carbonyl]-2-ethylpiperazin-1-yl]-6-(2-ethoxypyridin-3-yl)pyrazine-2-carboxylate To a 15-mL pressure tube vessel, was placed 66-bromo-3-[(2R)-4-[(tert-butoxy)carbonyl]-2-ethylpiperazin-1-yl]pyrazine-2-carboxylate (100 mg, 0.23 mmol), <strong>[854373-97-0]2-ethoxypyridine-3-boronic acid</strong> (78 mg, 0.46 mmol), PdCl2(t-Bu2PPhNMe2)2(24 mg, 0.033 mmol), K2CO3 (64 mg, 0.46 mmol), and dioxane/H2O (2.5 mL/0.25 mL). The resulting solution was degassed with N2 for 5 min and then sealed with a cap. The reaction was stirred at 100 C. for 1 h in an oil bath. The resulting mixture was cooled to rt, diluted with EtOAc, and washed with 1N-HCl and brine. The organic layer was dried with anhydrous Na2SO4 and concentrated. The residue was purified from C18 reversed phase column chromatography eluting with 0.1% TFA-ACN/0.1% TFA-H2O to afford methyl 3-[(2R)-4-[(tert-butoxy)carbonyl]-2-ethylpiperazin-1-yl]-6-(2-ethoxypyridin-3-yl)pyrazine-2-carboxylate (85 mg, 77%). LCMS (M+H)+: 472.3. |
Tags: 854373-97-0 synthesis path| 854373-97-0 SDS| 854373-97-0 COA| 854373-97-0 purity| 854373-97-0 application| 854373-97-0 NMR| 854373-97-0 COA| 854373-97-0 structure
[ 163105-90-6 ]
2-Methoxy-3-pyridineboronic acid
Similarity: 0.97
[ 1150114-42-3 ]
(2-Isopropoxypyridin-3-yl)boronic acid
Similarity: 0.96
[ 1245898-82-1 ]
(2-(tert-Butoxy)pyridin-3-yl)boronic acid
Similarity: 0.93
[ 1300750-50-8 ]
(2-(Difluoromethoxy)pyridin-3-yl)boronic acid
Similarity: 0.88
[ 221006-70-8 ]
2,6-Dimethoxypyridin-3-ylboronic acid
Similarity: 0.82
[ 163105-90-6 ]
2-Methoxy-3-pyridineboronic acid
Similarity: 0.97
[ 1150114-42-3 ]
(2-Isopropoxypyridin-3-yl)boronic acid
Similarity: 0.96
[ 1245898-82-1 ]
(2-(tert-Butoxy)pyridin-3-yl)boronic acid
Similarity: 0.93
[ 1300750-50-8 ]
(2-(Difluoromethoxy)pyridin-3-yl)boronic acid
Similarity: 0.88
[ 221006-70-8 ]
2,6-Dimethoxypyridin-3-ylboronic acid
Similarity: 0.82
[ 163105-90-6 ]
2-Methoxy-3-pyridineboronic acid
Similarity: 0.97
[ 1150114-42-3 ]
(2-Isopropoxypyridin-3-yl)boronic acid
Similarity: 0.96
[ 1245898-82-1 ]
(2-(tert-Butoxy)pyridin-3-yl)boronic acid
Similarity: 0.93
[ 1300750-50-8 ]
(2-(Difluoromethoxy)pyridin-3-yl)boronic acid
Similarity: 0.88
[ 221006-70-8 ]
2,6-Dimethoxypyridin-3-ylboronic acid
Similarity: 0.82
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