Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 402718-29-0 | MDL No. : | MFCD07780755 |
Formula : | C12H15BN2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BOIKCRIMIQAFQJ-UHFFFAOYSA-N |
M.W : | 230.07 | Pubchem ID : | 16414216 |
Synonyms : |
|
Num. heavy atoms : | 17 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.5 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 65.43 |
TPSA : | 55.14 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -6.6 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.56 |
Log Po/w (WLOGP) : | 1.25 |
Log Po/w (MLOGP) : | -0.08 |
Log Po/w (SILICOS-IT) : | 1.3 |
Consensus Log Po/w : | 0.81 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.44 |
Solubility : | 0.827 mg/ml ; 0.00359 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.33 |
Solubility : | 1.08 mg/ml ; 0.0047 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.72 |
Solubility : | 0.044 mg/ml ; 0.000191 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.88 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With hydrazine hydrate; caesium carbonate In water at 120℃; for 16 h; | 25 mL of the reaction flask was added hydrazine hydrate (0.25 mmol)5-Cyano-pyridine-3-boronic acid pinacol ester (0.5mmol),Cesium carbonate (1.0 mmol),Water (2.5 mmol)And polyethylene glycol-2000 (2.0 g).The reaction mixture was reacted at 120 ° C until the reaction was complete.The reaction mixture was cooled to room temperature,The product was isolated by column chromatography after evaporation of the solvent under reduced pressure,Yield 85percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 41 N-(((5S)-3-(4-((Z)-2-bromo-2-(5-cyanopyridin-3-yl)ethenyl)-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)acetamide The desired product was prepared by substituting 5-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)-nicotinonitrile (27.6 mg, prepared according to the procedure described in Tetrahedron Letters, 1997, 38, 3447-3450) for 3-aminophenylboronic acid in Example 40. MA (ESI(+)) m/e 459 (M+H)+; 1H NMR (300 MHz, CDCl3) delta9.08 (s, 1H), 8.83 (s, 1H), 8.23 (t, J=2.1 Hz, 1H), 8.07 (t, J=8.7 Hz, 1H), 7.58 (dd, J=2.1, 12.5 Hz, 1H), 7.39 (s, 1H), 7.28 (dd, J=2.1, 8.4 Hz, 1H), 4.8 (m, 1H), 4.08 (t, J=9 Hz, 1H), 3.83 (dd, J=6.6, 9.6 Hz, 1H), 3.6-3.75 (m, 2H), 2.04 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tris-(dibenzylideneacetone)dipalladium(0); tri tert-butylphosphoniumtetrafluoroborate; In water; tert-butyl alcohol; at 60℃; for 1h; | Method LL1 L3To a solution of bromide L1 (500 mg, 0.872 mmol, 1.0 equiv.) and boronic ester (300 mg, 1.30 mmol, 1.5 equiv.) in 3 ml_ tBuOH were added Tris- (dibenzylideneacetone)dipalladium (0) (119 mg, 0.130 mmol, 0.15 equiv.) and Tri-t- butylphosphonium tetrafluoroborate (119 mg) followed by aqueous K2CO3 (1 M, 1.30 mL, 1.30 mmol, 1.5 equiv.). The resulting mixture was heated at 60 0C for 1 hr and TLC indicated completion of reaction. The reaction mixture was diluted with ethyl acetate and wash with water. The organic layer was dried with MgSO4, concentrated and purified via a silica gel column with ethyl acetate in hexanes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 85℃; for 3h; | Example 18; 5-{4-[3-({2R}-2-Methyl-pyrrolidin-1-yl)-trans-cyclobutyl]-phenyl}-nicotinonitrile; Example 18A; 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile; A mixture of 5-bromo-3-cyano pyridine (5 g), pinacolatodiborane (9.02 g, 1.3 eq), PdCl2(dppf):CH2Cl2 (0.67 g, 0.03 eq), dppf (0.41 g, 0.03 eq) and potassium acetate (8.04 g, 3 eq) in dioxane (100 ml) was heated to 85 C. under nitrogen for 3 hours. The mixture was cooled to room temperature, diluted with 100 ml ethyl acetate and the solid was filtered off. The filtrate was concentrated to black oil (14.5 g). Chromatography (silica gel, 5:95 methanol:chloroform) gave yellow crystals (6.67 g). This was slurried with 60 ml hexane and the precipitate was filtered and vacuum dried at 45 C. to give the title compound (4.5 g). | |
With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85℃; for 12h;Inert atmosphere; | A reaction vessel containing a mixture of 5-bromonicotinonitrile (0.5 g, 2.73 mmol), 4,4,4',4',5,5,5',5,-octamethyl-2,2,-bi(l,3,2-dioxaborolane) (0.93 g, 3.54 mmol), and potassium acetate (0.80 g, 8.19 mmol) in 1,4-dioxane (30 mL) was purged with argon for 10 min. Next, l,l'-bis(diphenylphosphino)ferrocene (0.045 g, 0.0819 mmol) and [1,1- bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (0.066 g, 0.0819 mmol) were added and the reaction mixture was heated at 85 C for 12 h. The reaction mixture was cooled to room temperature filtered through a bed of CELITE and the bed was washed with ethyl acetate. The filtrate was concentrated under reduced pressure to afford the crude product 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile. MS (M+l): 231.1. | |
With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; tricyclohexylphosphine; In 1,4-dioxane; at 80℃; | Step 1 : 3-Cyano-5-(4,4,5,5-tetrameth -l,3,2-dioxaborolan-2-yl) pyridine To a 50 mL flask is added 5-bromo-3-cyanopyridine (0.50 g , 2.7 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2,-bis(l,3,2-dioxaborolane) (0.832 g, 3.3 mmol), Pd2(dba)3 (75 mg, 0.08 mmol), PCy3 (46 mg, 0.16 mmol), potassium acetate (0.803 g, 3.0 mmol), and 1,4-dioxane (10 mL). The reaction mixture is stirred at 80 C overnight. Then, it is treated with water (40 mL), and extracted with ethyl acetate (3 X 30 mL). The organic layer is isolated, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is used in next reaction without further purification. (MS: [M+l] 231) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 105℃; for 4.5h; | In a 6 ml vial for microwave with crown cap and magnetic stir bar, a mixture of 50 mg (0.137 mmol) of 3-bromo-6-(4-methanesulfonyl-phenyl)-2-methyl-imidazo[1 ,2-b]pyridazine (preparation see Stage 19.1), 32 mg (0.139 mmol) of 3-cyanopyridine-5-boronicacid pinacol ester (Frontier), 0.34 ml of a aqueous 1 M K2CO3-solution, 6 mg Pd(PPh3)2CI2 (Fluka) in 1.5 ml DMF is heated under argon in a oil bath at 1050C for 4 VT. h. The reaction mixture is poured into CH2CI2 and washed with water. After drying with Na2SO4 , the solvent is evaporated. The material obtained after chromatography on silicagel is triturated in diethylether to yield the title compound as a yellow solid. ES-MS: (M+1) = 390; HPLC: tR = 3.732 min.- |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Microwave irradiation; | Example 2l-(5'-Cvano-4-(4-(trifluoromethyl)thiazol-2-yl)-3,3'-bipyridin-6-yl)-3-ethylureal-(5-Bromo-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 3, 300 mg, 0.76 mmol), cesium carbonate (495 mg, 1.52 mmol),tetrakis(triphenylphosphine)palladium (0) (88 mg, 0.08 mmol), and 5-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)nicotinonitrile (349 mg, 1.52 mmol) were taken in a microwave vial and degassed with nitrogen. Then dioxane: water (4:1, 6 mL) was added to the vial and the mixture was microwaved at 100 0C for half an hour. The reaction mixture was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was back extracted with ethyl acetate (2-3 times). The combined organic layers were washed with saturated sodium bicarbonate solution, water, brine and dried over magnesium sulfate. The solvent was removed and the residue was washed with acetonitrile to give the title compound as a white solid (270 mg).MS (ESP): 419 (M+ 1) for C18Hi3FN6OS1H-NMR (DMSO-dfi) delta: 1.09 (t, 3H); 3.16-3.22 (m, 2H); 7.49 (t, 1 H); 8.22 (s, IH); 8.36 (s, IH); 8.38 (d, IH); 8.60 (s, IH); 8.76 (s, IH); 9.04 (s, IH); 9.52 (s, IH). | |
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Microwave irradiation; | Example 2 l-(5'-Cvano-4-(4-(trifluoromethyl)thiazol-2-yl)-3,3'-bipyridin-6-yl)-3-ethylurea l-(5-Bromo-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 3, 300 mg, 0.76 mmol), cesium carbonate (495 mg, 1.52 mmol), tetrakis(triphenylphosphine)palladium (0) (88 mg, 0.08 mmol), and 5-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)nicotinonitrile (349 mg, 1.52 mmol) were taken in a microwave vial and degassed with nitrogen. Then dioxane: water (4:1, 6 mL) was added to the vial and the mixture was microwaved at 100 0C for half an hour. The reaction mixture was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was back extracted with ethyl acetate (2-3 times). The combined organic layers were washed with saturated sodium bicarbonate solution, water, brine and dried over magnesium sulfate. The solvent was removed and the residue was washed with acetonitrile to give the title compound as a white solid (270 mg). MS (ESP): 419 (M+ 1) for Ci8Hi3FN6OS 1H-NMR (DMSO-d) delta: 1.09 (t, 3H); 3.16-3.22 (m, 2H); 7.49 (t, 1 H); 8.22 (s, IH); 8.36 (s, IH); 8.38 (d, IH); 8.60 (s, IH); 8.76 (s, IH); 9.04 (s, IH); 9.52 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.4% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 110℃; for 1.33333h;Microwave irradiation; | Example 26 5-(5-(3-Amino-4-fluoro-1-(pyridin-4-yl)-1H-isoindol-1-yl)-2-fluorophenyl)nicotinonitrile 3-Cyanopyridine-5-boronic acid pinacol ester (58.1 mg, 0.25 mmol), 1-(3-bromo-4-fluorophenyl)-4-fluoro-1-(pyridin-4-yl)-1H-isoindol-3-amine (67.4 mg, 0.17 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (6.88 mg, 8.42 mumol), 2 M aqueous potassium carbonate (0.253 mL, 0.51 mmol) and DMF (2.00 mL) were put in a microwave vial and irradiated in a microwave oven at 110 C. for 20 min. Additional <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (25.2 mg, 0.11 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (6.88 mg, 8.42 mumol) were added and the resulting mixture was irradiated at 110 C. for 30 min. Additional <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (25.2 mg, 0.11 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (6.88 mg, 8.42 mumol) were added and the resulting mixture was irradiated at 110 C. for 30 min. The product was purified by preparative HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was partitioned between water and ethyl acetate (*3). The organic layer was collected, dried (Na2SO4), filtered and concentrated in vacuo. The residue was redissolved in methanol and concentrated in vacuo three times to give the title compound 5.80 mg, (7.4% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 9.05 (d, 1H) 8.93-8.99 (m, 1H) 8.40-8.56 (m, 3 H) 7.78 (d, 1H) 7.46-7.63 (m, 3H) 7.36 (t, 1H) 7.28 (d, 3H) 6.70 (br. s., 1H) 1.91 (s, 2H); MS (ES+) m/z 424 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.6% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 110℃; for 1.66667h;Microwave irradiation; | Example 25 5-(5-(3-Amino-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-1-yl)-2-fluorophenyl)nicotinonitrile trifluoroacetate 3-Cyanopyridine-5-boronic acid pinacol ester (85 mg, 0.37 mmol), 1-(3-bromo-4-fluorophenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (115.5 mg, 0.25 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol), 2 M aqueous potassium carbonate (0.370 mL, 0.74 mmol) and DMF (2.00 mL) were put in a microwave vial and irradiated in a microwave oven at 110 C. for 20 min. Additional <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (36.9 mg, 0.16 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated at 110 C. for 20 min. Additional <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (36.9 mg, 0.16 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated at 110 C. for 30 min. Additional <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (36.9 mg, 0.16 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (10.07 mg, 0.01 mmol) were added and the resulting mixture was irradiated for 30 min. The resulting product mixture was filtered and purified by preparative-HPLC to give the title compound 11.4 mg, (7.6% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 11.78 (br. s., 1H) 10.11 (br. s., 1H) 9.56 (br. s., 1 H) 9.08 (dd, J=1.73, 0.31 Hz, 1H) 9.02 (t, J=1.89 Hz, 1H) 8.77-8.89 (m, 1H) 8.47-8.54 (m, 1H) 7.95 (br. s., 1H) 7.79-7.89 (m, 2H) 7.70 (ddd (m), 1H) 7.56-7.66 (m, 2H) 7.41-7.55 (m, 2H); MS (ES-) m/z 490 [M+H]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.8% | With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 1h;Biotage "Initiator" microwave; | Example 192:5-(2-[2-[(trans-4-hydroxycyclohexyl)amino]-6-(1-piperidinylmethyl)-4-pyrimidinyl]amino}-1,3-benzothiazol-6-yl)-3-pyridinecarbonitrileA mixture of trans-4-[4-[(6-bromo-1,3-benzothiazol-2-yl)amino]-6-(1-piperidinylmethyl)-2-pyrimidinyl]amino}cyclohexanol (100mg, 0.193mmol), 5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3-pyridinecarbonitrile (89mg, 0.386mmol), tetrakis(triphenylphosphine)Pd(0) (44.7mg, 0.039mmol) and potassium phosphate (61.5mg, 0.290mmol) in 1 ,4-dioxane (7mL) and water (2mL) was sealed and heated in a Biotage "Initiator" microwave at 1000C for 1 hour. The reaction mixture was then added to water (5OmL) and the crude product filtered off and dried. The product was purified by mass-directed automated preparative HPLC (ammonium bicarbonate modifier) to afford the title compound (6.1 malpha. O.OH mmol, 5.8% yield). LCMS (Method A) Rt: 0.72 minutes; m/z: 541 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; water; at 20 - 60℃; | Aqueous sodium carbonate solution (0.1 M, 0.5 mL) was added to a THF (2.0 mL) solution of Intermediate Tf-2(20 mg), <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> (which may be referred to as sbo96; 29.0 mg; FRON), and PdCl2dppf.CH2Cl2 (4.0 mg) at room temperature and the resulting mixture was stirred at 60 C. for 15 hours. The reaction mixture solution was filtrated through celite and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Yamazen; chloroform/methanol) to give the title compound (18.3 mg).(LCMS: 422.3 (MH+); retention time: 1.09 min; LCMS; condition A) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Suzuki reaction procedure: To a sealed Biotage microwave vial was added DMF (3 niL) and 2 drops Of H2O and the system was sparged with argon for 10 minutes. A second vial was charged with 4-64 (0.08 g, 0.177 mmol), 5-(4,4,55-tetramethyl-l,3,2-dioxaboroIan-2- yl)mcotinonitrile (0.049 g, 0.212 mmol), Cs2CO3 (0.1 ISg5 0.354 mmol), and Pd(PPh3)4 (0.03Og, 0.027 mmol). The tube was sealed with a cap lined with a Teflon septum and the DMF/H2O mixture above (3 mL) was added via a syringe. The reaction was sparged with argon for another 5 minutes, then heated to 85 0C for 12 hr. The reaction was cooled to rt and filtered through a thin pad of silica gel and filter agent. The solvent was concentrated and the crude product was purified by silica gel CombiFlash chromatography (eluting with 0 - 10% MeOH in dichioromethane). The material was then purified by semi prep HPLC and lyophilized from aq. HCI/CH3CN to give compound 5-10 ( 0.053 g, 0.104 mmol, 59%) as an off white solid. MS (ESI): 476 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With water; sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; at 80℃; for 2h; | 2-(3-Bromophenyl)-2-(4-methoxyphenyl)-5-methyl-2H-imidazol-4-amine (96 mg, 0.27 mmol), 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (61.7 mg, 0.27 mmol) and bis(triphenylphosphine)palladium(II) chloride (37.6 mg, 0.05 mmol) were taken up in DME (2 mL) and water (1 mL). Sodium carbonate (IM in water) (0.670 mL, 0.67 mmol) was added and the reaction was heated to 80 0C for 2 h. The reaction mixture was filtered and preparative HPLC yielded 19.7 mg (19% yield) of the title compound: 1H NMR (400 MHz, methanol-*/*) delta ppm 9.00 (d, 1 H) 8.85 (d, 1 H) 8.39 (t, 1 H) 7.70 (s, 1 H) 7.60 (d, 1 H) 7.50 - 7.56 (m, 1 H) 7.40 - 7.49 (m, 1 H) 7.28 (d, 2 H) 6.83 (d, 2 H) 3.74 (s, 3 H) 2.37 (s, 3 H); MS (ES+) m/z 382 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90℃; for 1h; | D. 5'-(5-Cyano-pyridin-3-yl)-3'-(4-methoxy-phenoxy)-2,3,5,6-tetrahydro-[1,2]bipyrazinyl-4-carboxylic acid tert-butyl ester (7e). In a teflon-lined septum sealed Schlenk tube, a mixture of Compound 7d (120 mg; 0.26 mmol), Compound 5a (89 mg; 0.387 mmol), Na2CO3/H2O (55 mg; 0.52 mmol in 0.4 mL H2O) and [1,1'-Bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) (21 mg, 0.026 mmol) in dioxane (2 mL) was heated at 90 C. for 1 h. The resultant mixture was diluted with EtOAc, washed with saturated NH4Cl (aq) and H2O. The organic phase was washed with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was concentrated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 7e (100 mg; 79% yield). MS: m/z 489.2 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; acetonitrile; at 140℃; for 0.333333h;Microwave irradiation; | A. 2-(S)-[5-(5-Cyano-pyridin-3-yl)-pyrazin-2-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (5b). To a teflon-lined septum sealed Schlenk tube, a mixture of Compound 3b (2.0 g; 5.60 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile (Compound 5a) (1.55 g; 6.72 mmol), K2CO3 (1.547 g; 11.2 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) (274 mg, 0.336 mmol) in a mixture of CH3CN (8 mL) and H2O (2 mL) was irradiated in a microwave reactor at 140 C. for 20 minutes. The resultant mixture was diluted with EtOAc, and then washed with saturated NH4Cl (aq) and H2O. The organic phase was washed with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was concentrated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 5b (1.56 g; 73% yield) as tan powder. 1H-NMR (400 MHz, CDCl3): delta 9.27 (d, 1H), 8.79 (s, 1H), 8.42-8.52 (m, 2H), 8.00 (d, 1H), 7.09 (br. s., 1H), 4.05-4.34 (m, 1H), 3.30-3.59 (m, 4H), 2.03-2.17 (m, 1H), 1.86-2.01 (m, 2H), 1.73-1.84 (m, 1H), 1.50 (s, 9H); MS: m/z 381.2 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium phosphate; In 1,4-dioxane; water; at 130℃; for 0.5h;Sealed tube; Microwave irradiation; | Example 85:5-(2-[6-[(trans-4-hydroxycyclohexyl)amino]-4-(1H-pyrazol-1 -ylmethyl)-2- pyridinyl]amino}-1,3-benzothiazol-6-yl)-3-pyridinecarbonitrileA mixture of trans-4-[6-[(6-bromo-1 ,3-benzothiazol-2-yl)amino]-4-(1 H-pyrazol-1 -ylmethyl)- 2-pyridinyl]amino}cyclohexanol [example 78] (100mg, 0.20mmol), tetrakis(triphenylphosphine)palladium(0) (34.7mg, 0.03mmol), potassium phosphate (85mg, 0.40mmol) and 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinecarbonitrile (83, 0.36mmol) in a mixture of 1 ,4-dioxane (4mL) and water (1.3mL) was sealed and heated in a Biotage "Initiator" microwave at 130C for 30 minutes. The reaction mixture was added to a mixture of dichloromethane (50ml_) and water (50ml_). After stirring for 15 minutes, the mixture was filtered and the filtered solid washed with water and dried. The solid was dissolved in DMSO (2ml_) and the product was subjected to purification by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (57mg, 0.1 1 mmol, 55% yield). LCMS (Method B): Rt 0.88 minutes; m/z 523 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 0.75h; | Example 87:5-[2-({6-[(trans-4-hydroxycyclohexyl)amino]-4-[(2-methyl-1H-imidazol-1 -yl)methyl]-2- pyridinyl}amino)-1,3-benzothiazol-6-yl]-3-pyridinecarbonitrileA mixture of trans-4-({6-[(6-bromo-1 ,3-benzothiazol-2-yl)amino]-4-[(2-methyl-1 H-imidazol- 1-yl)methyl]-2-pyridinyl}amino)cyclohexanol [example 79] (100mg, 0.20mmol), tetrakis(triphenylphosphine)palladium(0) (45.0mg, 0.039mmol), potassium phosphate (62.0mg, 0.29mmol) and 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinecarbonitrile (90mg, 0.39mmol) in a mixture of 1 ,4-dioxane (1.5ml_) and water (0.5ml_) was sealed and heated in a Biotage "Initiator" microwave at 100C for 45 minutes. The reaction mixture was added to a mixture of chloroform (50ml_), methanol (5ml_) and water (50ml_). After stirring for 15 minutes, the mixture was filtered and the filtrate separated. The organic phase was evaporated to dryness, combined with the filtered solid and purified by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (58.4mg, 0.1 1 mmol, 56% yield). LCMS (Method B): Rt 0.72 minutes; m/z 537 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 0.75h;Sealed tube; Microwave irradiation; | Example 101 :5-{2-[(4-[(2-methyl-1H-imidazol-1-yl)methyl]-6-[3-(4-morpholinyl)propyl]amino}-2- pyridinyl)amino]-1 ,3-benzothiazol-6-yl}-3-pyridinecarbonitrileA mixture of A/-(6-bromo-1 ,3-benzothiazol-2-yl)-4-[(2-methyl-1 H-imidazol-1-yl)methyl]-A/'- [3-(4-morpholinyl)propyl]-2,6-pyridinediamine [example 99] (165mg, 0.30mmol), 3- cyanopyridine-5-boronic acid pinacol ester (140mg, 0.61 mmol), tetrakis(triphenylphosphine)palladium(0) (70.3mg, 0.061 mmol) and potassium phosphate (97mg, 0.46mmol) in 1 ,4-dioxane (7ml_) and water (2mL) was sealed and heated in a Biotage "Initiator" microwave at 100C for 45 minutes. Water (100ml_) was added and the reaction mixture was filtered. The filtered solid was washed with water, dried and subjected to purification by mass-directed automated preparative HPLC (trifluoroacetic acid modifier) followed by passing the recovered salt through an aminopropyl solid-phase extraction cartridge using methanol as eluant to afford the title compound (60mg, 0.106mmol, 35% yield). LCMS (Method B): Rt 2.42 minutes; m/z 566 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 0.75h;Sealed tube; Microwave irradiation; | Example 136:5-[2-({4-(aminomethyl)-6-[(trans-4-hydroxycyclohexyl)amino]-2-pyridinyl}amino)-1 ,3- benzothiazol-6-yl]-3-pyridinecarbonitrileA mixture of tetrakis(triphenylphosphine)palladium(0) (41 .2mg, 0.036mmol), trans-4-({4- (aminomethyl)-6-[(6-bromo-1 ,3-benzothiazol-2-yl)amino]-2-pyridinyl}amino)cyclohexanol [example 135] (80mg, 0.178mmol), potassium phosphate (56.8mg, 0.27mmol) and 5- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3-pyridinecarbonitrile (82mg, 0.36mmol) in a mixture of 1 ,4-dioxane (1.5mL) and water (0.5mL) was sealed and heated in a Biotage "Initiator" microwave at 100C for 45 minutes. The reaction mixture was evaporated to dryness and purified by mass-directed automated preparative HPLC (ammonium bicarbonate modifier) to afford the title compound (29mg, 0.061 mmol, 35% yield). LCMS (Method A): Rt 0.68 minutes; m/z 472 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 3.5h;Sealed tube; Microwave irradiation; | Intermediate 45:5-[2-({4-formyl-6-[(frans-4-hydroxycyclohexyl)amino]-2^yridinyl}amino)-1 ,3- inecarbonitrileA mixture of 2-[(6-bromo-1 ,3-benzothiazol-2-yl)amino]-6-[(trans-4- hydroxycyclohexyl)amino]-4-pyridinecarbaldehyde [intermediate 44] (357mg, 0.798mmol), tetrakis(triphenylphosphine)palladium(0) (46.1 mg, 0.04mmol), potassium phosphate (254mg, 1 .20mmol) and 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinecarbonitrile (367mg, 1 .60mmol) in a mixture of 1 ,4-dioxane (6ml_) and water (2ml_) was sealed and heated in a Biotage "Initiator" microwave at 100C for 3.5 hours. The reaction mixture was evaporated to dryness and the residue was taken up in tetrahydrofuran and filtered. The filtrate was evaporated to dryness and the product was purified by chromatography on silica using a gradient elution from 0 to 100% ethyl acetate in dichloromethane followed by 0 to 20% methanol in dichloromethane to afford the title compound (147mg, 0.31 mmol, 39% yield). LCMS (Method A): Rt 0.92 minutes; m/z 471 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere; Sealed vial; | A reaction vial was charged with (4S,4a'S, 10a'R)-2-amino-8'-bromo- 1 -methyl- 3^4^4a l0a'-tetrahydro-2-spiro[imidazole-4,10'-pyrano[3,2-b]chromen]-5(lH)-one (30 mg, 0.082 mmol), 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (38 mg, 0.164 mmol), Pd(PPh3)4 (9.5 mg, 0.008 mmol), 2M aqueous potassium carbonate (0.123 mL, 0.246 mmol) in dioxane (1 mL). This mixture was purged with argon for 5 minutes, and the vial was sealed and heated to 100C for 16 hours. The mixture was diluted with EtOAc and washed with water, and the organics were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative thin layer chromatography to give 5-((4S,4a'S, 10a'R)-2-amino- 1 -methyl-5-oxo-l ,3',4',4a',5, 10a'-hexahydro-2'H- spiro[imidazole-4,10'-pyrano[3,2-b]chromen]-8'-yl)mcotinonitrile (13 mg, 41%). 1H NMR (400 MHz, CDCI3) delta 8.92-8.90 (m, 1H), 8.79-8.77 (m, 1H), 8.03-8.00 (m, 1H), 7.42-7.37 (m, 1H), 7.16-7.12 (m, 1H), 7.04-6.99 (m, 1H), 4.86-4.77 (m, 1H), 3.96-3.90 (m, 1H), 3.55-3.50 (m, 1H), 3.40-3.31 (m, 1H), 3.13 (s, 3H), 2.41-2.33 (m, 1H), 1.86-1.55 (m, 3H); m/z (APCI- pos) M+l = 390.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Example 63; 5-((2'S*,4a'S*<9a'R* 2-amino-2,-hvdroxy-1 2^3 4 4a 9a'-hexahvdro-5H-spiroroxazole-4.9'- xanthen1-7 l nicotinonitrile; Step A:; A solution of (4a'S,9a'R)-2-amino-7'-bromo-r,4',4a',9a,-tetrahydro-5H- spiro[oxazole-4,9'-xanthen]-2'(3'H)-one (25.0 mg, 0.071 mmol; Example 23, Step G), 5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (17.2 mg, 0.075 mmol), Pd(PPh3)4 (4.1 mg, 0.0036 mmol), 2M Na2C03 (107 mu,, 0.214 mmol) in dioxane (356 mu,) was degassed with nitrogen for 5 minutes, sealed in a vial and stirred at 80C for 1 day. The reaction mixture was partitioned between 4N HCl and ethyl acetate. The organic layer was extracted with 4N HCl, and the combined aqueous layers were cooled to 0C and basified with KOH pellets. The basic (greater than pH 10) aqueous layer was extracted with ethyl acetate (5 X), and the combined organic layers were dried and concentrated to afford 5-((4a'S*,9a'R*)-2-amino-2'-oxo- 1^2^3',4',4a,,9a'-hexahydro-5H-spiro[oxazole-4,9'-xanthene]-7'-yl)nicotinonitrile (17 mg, 0.045 mmol, 64% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; microwave vial; | Step 6: 4-Amino-6-({l-[5-chloro-3-(5-cyanopyridin~3-yl)-4-fluoro-2- methoxyphenyl] ethyl} amino)pyrimidine-5-carbonitrileInto a microwave vial was added 4-amino-6-[l -(3-bromo-5-chloro-4-fluoro-2- methoxyphenyl)ethyl]amino}pyrimidine-5-carbonitrile (8.0 mg, 0.020 mmol), 5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (5.51 mg, 0.0240 mmol), a solution of sodium carbonate (48 uL, 0.050 mmol) in water (48 1,4-dioxane (0.2 mL, 2 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.4 mg, 0.0012 mmol). The mixture was bubbled with N2 for 5 minutes and heated at 90 C for 2h. Purification by preparative LCMS (pH 10) gave the desired compound (37% yield). LCMS calculated for C20H1 6CIFN7O(M+H)+: m/z = 424.1 ; found: 424.1. ]H NMR (DMSO-i&, 500 MHz) delta 9.12 (s, 1 H), 8.97 (s, 1 H), 8.50 (s, 1 H), 7.95 (s, 1 H), 7.88 (m, 1 H), 7.70 (m, 1 H), 7.22 (br s, 2 H), 5.63 (m, 1 H), 3.41 (s, 3 H), 1.42 (m, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium carbonate; triphenylphosphine;palladium diacetate; In dimethoxyethane-1,2; at 105℃; for 15h;Inert atmosphere; Sealed tube; | Example 95-[3-((4R,5R)-2-Amino-5-fluoro-4-methyl-5,6-dihydro-4H-[l,3]oxazin-4-yl)-4-fluoro- phenyl] -nicotinonitrile a) 5-[3-((4R,5R)-2-{ [Bis-(4-methoxy-phenyl)-phenyl-methyl] -amino } -5-fluoro-4- methyl-5,6-dihydro-4H-[l,3]oxazin-4-yl)-4-fluoro-phenyl]-nicotinonitrileIn a dry tube under an atmosphere of argon to a solution of [bis-(4-methoxy-phenyl)- phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H- [l,3]oxazin-2-yl]-amine (intermediate C4.3) (250 mg, 412 muiotaetaomicron) and 5-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)nicotinonitrile (142 mg, 617 muiotaetaomicron) in 1,2-dimethoxyethane (3 ml) were added consecutively an aqueous solution of sodium carbonate (2M, 0.6 ml), triphenylphosphine (22.3 mg, 82.3 muiotaetaomicron), and, after flushing the mixture with argon, palladium(II)acetate (9.24 mg, 41.2 muiotaetaomicron). The tube was sealed and heated under stirring at 105 C for 15 hours. After evaporation at reduced pressure, the residue was purified by chromatography on a silica-NH2 phase using a gradient of heptane/ethyl acetate = 100:0 to 60:30 as the eluent. The 5-[3- ((4R,5R)-2-{ [bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-5-fluoro-4-methyl-5,6-dihydro- 4H-[l,3]oxazin-4-yl)-4-fluoro-phenyl]-nicotinonitrile (260 mg, 100% yield) as a white foam. MS (ISP): m/z = 631.4 [M+H]+. |
100% | With sodium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 105℃; for 15h;Inert atmosphere; Sealed vessel; | a) 5-[3-((4R,5R)-2-[Bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-nicotinonitrile In a dry tube under an atmosphere of argon to a solution of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine (intermediate C4.3) (250 mg, 412 mumol) and <strong>[402718-29-0]5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile</strong> (142 mg, 617 mumol) in 1,2-dimethoxyethane (3 ml) were added consecutively an aqueous solution of sodium carbonate (2M, 0.6 ml), triphenylphosphine (22.3 mg, 82.3 mumol), and, after flushing the mixture with argon, palladium(II)acetate (9.24 mg, 41.2 mumol). The tube was sealed and heated under stirring at 105 C. for 15 hours. After evaporation at reduced pressure, the residue was purified by chromatography on a silica-NH2 phase using a gradient of heptane/ethyl acetate=100:0 to 60:30 as the eluent. The 5-[3-((4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-nicotinonitrile (260 mg, 100% yield) as a white foam. MS (ISP): m/z=631.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; acetonitrile; at 110℃; for 0.333333h;Microwave irradiation; | General procedure: To a solution of 6-Bromo-1-(2-trimethylsilanylethoxyrnethyl)-1H-indazole-3-carboxylic acid (1-thiazol-4-ylmethyl-1H-pyrazol-4-yl)amide (49.0 mg, 0.0918 mmol) in acetonitrile (1 mL) was added 1H-pyrazole-2-boronic acid (20.6 mg, 0.184 mmol), 1,1'-Bis(diphenylphosphino)ferrocenepalladium (II) chloride (7.50 mg, 0.00918 mmol) and sodium carbonate (29.2 mg, 0.276 mmol) as a 1.0 M solution in water. The mixture was heated to 110 C for 20 minutes in the microwave, then cooled to rt. The mixture was diluted with 5 mL CH2Cl2 and 5 mL brine and filtered through a phase separator. After in vacuo concentration, the residue was diluted with TFA (1 mL), triisopropylsilane (93 muL, 0.45 mmol) and a few drops of CH2Cl2 to homogenize, and the mixture was stirred at 90 minutes at rt. After in vacuo concentration, the residue was purified by automated reverse phase HPLC to provide the title compound (12 mg; 0.0297 mmol; 33%). 1H NMR (400 MHz, DMSO) delta 13.68 (s, 1H), 12.95 (s, 1H), 10.57 (s, 1H), 9.10 (d, J= 1.9 Hz, 1H), 8.21 (d, J= 8.5 Hz, 1H), 8.18 (s, 1H), 7.99 (s, 1H), 7.79 (s, 1H), 7.73 (s, 1H), 7.56 (d, J= 1.7 Hz, 1H), 6.83 (s, 1H), 5.45 (s, 2H). MS: m/z = 391.1 (M+H) + .The title compound was synthesized according to example 43, substituting <strong>[402718-29-0]3-cyanopyridine-5-boronic acid pinacol ester</strong> for 1H-pyrazole-2-boronic acid. 1H NMR (400 MHz, DMSO) delta 13.97 (s, 1H), 10.65 (s, 1H), 9.29 (d, J= 2.2 Hz, 1H), 9.10 (d, J= 1.9 Hz, 1H), 9.05 (d, J= 1.8 Hz, 1H), 8.76 (t, J= 2.0 Hz, 1H), 8.34 (d, J= 8.5 Hz, 1H), 8.19 (s, 1H), 8.05 (s, 1H), 7.73 (s, 1H), 7.71 (d, J= 8.5 Hz, 1H), 7.57 (d, J= 1.7 Hz, 1H), 5.46 (s, 2H). MS: m/z = 427.1 (M+H) + . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; acetonitrile; at 95℃; for 2h;Inert atmosphere; | A mixture of 1-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (first peak from Example 167, step 4 chiral separation, 106 mg, 0.25 mmol), <strong>[402718-29-0]5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile</strong> (70.0 mg, 0.31 mmol, from Combi-Blocks Catalog, item No. PN-8893), sodium carbonate (43 mg, 0.41 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (33 mg, 0.041 mmol) in acetonitrile (2 mL)/water (0.6 mL) was degassed with N2 and then stirred at 95 C. for 2 h. The mixture was diluted with methylene chloride, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product (95 mg, 87%) was purified by chromatography eluting with CH2Cl2/MeOH (max. MeOH 5%). LCMS calculated for C22H21ClN7O (M+H)+: m/z=434.2; Found: 434.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.166667h;Microwave irradiation; | 3-bromo-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 3.1, 50 mg, 0.139 mmol), 5-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (0.180 mmol), 2 M Na2C03 (0.104 mL, 0.208 mmol), (Ph3P)4Pd (8 mg, 6.94 muetaiotaomicron), water (0.8 mL) and DME (2.4 mL) were added to a vial, which was sealed and subjected to MW irradiation at 150C for 10 min. The RM was filtered through a PL-Thiol MP SPE cartridge (StratoSpheres, 6 mL) and the cartridge was washed with MeOH (10 mL). The combined filtrates were evaporated to dryness under reduced pressure and the crude product was purified by preparative HPLC to afford the title compound. LC-MS (Condition 5) tR = 1.24 min, m/z = 384.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 120℃; for 0.166667h;Microwave irradiation; Sealed tube; Inert atmosphere; | [00350] (R)-5-Bromo-6-(3-hydroxypyrrolidin- 1 -yl)-N-(4- (trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 200 mg, 0.448 mmol), 5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)nicotinonitrile (206 mg, 0.896 mmol), Pd(PPh3)2Cl2 (31.5 mg, 0.045 mmol) and Na2CC>3 (143 mg, 1.345 mmol) were added to a MW vial and treated with a mixture of DME (1.902 mL), water (543 mu) and EtOH (272 muEpsilon) . The vial was sealed, evacuated / purged with argon and then the RM was subjected to MW irradiation at 120C for 10 min, then cooled to RT and finally treated with Si-Thiol (1.27 mmol/g, 176 mg, 0.224 mmol) overnight. The RM was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 12, 25% for 0.2 min then 25% to 55% in 14 min.) to yield the title compound as a white solid. UPLC-MS (condition 1) 1R = 2.30min, m/z = 470.0-471.0 [M+H , m/z = 468.0-469.0 [M-H]"; XH-NMR (400 MHz, DMSO-dg) delta ppm 1.70 - 1.79 (m, 1 H) 1.80 - 1.92 (m, 1 H) 2.86 (d, J = 11.25 Hz, 1 H) 3.16 - 3.27 (m, 2 H) 3.34 - 3.44 (m, 1 H) 4.17 - 4.24 (m, 1 H) 4.70 - 5.04 (m, 1 H) 7.35 (d, J = 8.80 Hz, 2 H) 7.82 - 7.88 (m, 2 H) 8.09 (d, J = 2.45 Hz, 1 H) 8.40 (t, J = 2.08 Hz, 1 H) 8.79 (d, J = 2.20 Hz, 1 H) 8.90 (d, J = 1.96 Hz, 1 H) 9.02 (d, J = 1.96 Hz, 1 H) 10.17 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
200 mg | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 100℃; | Step 2: 2-Chloro-6-(5-cyanopyridin-3-yl)pyridazine To a 50 mL flask is added 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3- cyanopyridine (0.523 g, 2.7 mmol), 3,6-dichloropyridazine (0.611 g, 4.1 mmol), Pd(PPh3)4 (158 mg, 0.014 mmol) , cesium carbonate (1.78 g, 5.5 mmol), and 1,4-dioxane (20 mL). The reaction mixture is stirred at 100 C overnight, filtered, and concentrated. The residue is purified on a silica gel flash chromatography with ethyl acetate/petroleum ether (1 : 1 ) to obtain the desired product as a brown solid (200 mg, 34% combined yield). (MS: [M+l] 217) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With palladium diacetate; triphenylphosphine; In 1,4-dioxane; at 100℃; for 15h;Green chemistry; | 1) 3 ml dioxane was placed in a dry reactor, under stirring conditions, a solution of 5-cyano-3-pyridineboronic acid ester (138 mg, 0.6 mmol)(261.6 mg, 1.2 mmol) was added to dioxane, palladium acetate (6.7 mg, 0.03 mmol) was added, triphenylphosphine (23.5 mg, 0.09 mmol), to obtain a mixture A. 2) under oil bath conditions, the mixture A obtained in step 1) was heated to 100 C to carry out the reaction, after 15h reaction, the reaction mixture was cooled to room temperature,to obtain a mixture B. 3) after the mixture B obtained in the step 2) was diluted with ethyl acetate, filtered through celite and washed with ethyl acetate, the filtrate was concentrated and dried to obtain crude product. The crude product was separated by column chromatography with ethyl acetate / petroleum ether = 1: 10 as the developing solvent to obtain 41 mg of the aimed product in a yield of 32%. The target product obtained in this Example was subjected to nuclear magnetic characterization, and the results were as follows: 1H NMR (400MHz, CDCl 3, ppm): delta9.32 (d, J = 1.9Hz, 1H), 8.99 (d, J = 1.9Hz, 1H), 8.48 (t, J = 1.9Hz, 1H), 1.61 (s, 9H). 13 C NMR (100MHz, CDCl 3, ppm): delta162.4 (s), 154.9 (s), 153.6 (s), 140.1 (S), 127.9 (s), 115.9 (s), 109.9 (s), 83.6 (s), 28.0 (s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 5h;Inert atmosphere; | To a stirred mixture of 1 -allyl-2-bromo-6-(4-chlorophenyl)-5-(3, 7-dimethyl-3H-benzo[d][1 ,2,3]triazol-5-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1 H)-one (Step 1.11) (80 mg, 0.161 mmol) in Dioxane (1.1 mL) and water (400 iL) under Ar were added K3P04 (136 mg,0.643 mmol), PdCI2(dppf).CH2CI2 adduct (20 mg, 0.0.24 mmol) and trimethylboroxine (45 iL,0.32 mmol). The resulting mixture was heated up and stirred at 100 00 overnight. PdCI2(dppf).CH2CI2 adduct (20 mg, 0.0.24 mmol) and trimethylboroxine (45 iL, 0.32 mmol) were added and the reaction was stirred 1.5 hr at 100 00 PdCI2(dppf).CH2CI2 (20 mg, 0.0.24 mmol) adduct and trimethylboroxine trimethylboroxine (45 iL, 0.32 mmol) were added and the reaction was stirred 5.5 hr at 100 00 The reaction was cooled down to RT, diluted with water and the aq. layer was extracted twice with EtOAc. Combined extracts were dried over Na2504, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (gradient 35-55 % CH3CN in 16 mm) followed by basic workup to afford the title product (5 mg, 0.012 mmol, 7.52 % yield). tR: 0.80 mm (LC-MS 2); ESl-MS: 393 [M+H] ESl-MS: 391 [M-H] (LC-MS 2).The title compound was prepared in analogy to the procedure described for Example 1 using 2- bromo-6-(4-chlorophenyl)-5-(1 ,5-dimethyl-6-oxo-1 ,6-dihydropyridin-3-yl)-3-propyl-5,6-dihydro- pyrrolo[3,4-d]imidazol-4(3H)-one (Step 36.8) and (5-cyanopyridin-3-yl)boronic acid pinacolester at 100 00 for 5 hr. The crude product was purified by silica gel column chromatography (hexane/(EtOAc/MeOH 9:1) 20-100 % (EtOAc/MeOH 9:1) to afford a beige amorphous solid. tR. 0.92 mm (LC-MS 2); ESl-MS: 499/501 [M+H] ESl-MS: 497 [M-H] (LC-MS 2); TLC (EtOAc/MeOH 9:1) Rf= 0.16; 1H NMR (400 MHz, DMSO-d6) O ppm 0.79 (t, J=7.3 Hz, 3 H) 1.84- 1.94 (m, 2 H) 1.96 (5, 3 H) 3.37 - 3.43 (m, 3 H) 4.26 (t, J=7.1 Hz, 2 H) 6.22 (5, 1 H) 7.30 (d, J=8.4 Hz, 2 H) 7.42 (d, J=8.4 Hz, 2 H) 7.47 (d, J=1.6 Hz, 1 H) 7.78 (d, J=2.7 Hz, 1 H) 8.65 (t, J=2.0 Hz, 1 H) 9.14 (d, J=2.2 Hz, 1 H) 9.16 (d, J=2.0 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.5% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 80℃; for 10h;Inert atmosphere; | General procedure: A mixture of 18a (100.00 mg, 0.21 mmol), cesium carbonate (139.20mg, 0.43 mmol), phenylboronic acid (34.00 mg, 0.28 mmol) and tetrakis(triphenylphosphine)palladium (0) (25.00 mg, 0.02 mmol) in dioxane (15 ml) and H2O (5 ml) wasdegassed and flushed with argon. The mixture was hearted at 80 C for 10 h. Thesolvent was evaporated under reduced pressure. The residue was diluted with H2O(20 ml) and extracted with ethyl acetate (30 ml ×2). The combined organiclayers were washed with H2O (20 ml ×2) and brine (20 ml ×2), driedover anhydrous Na2SO4, and filtrated, then the solventwas evaporated under reduced pressure. The residue was purified by silica gelcolumn chromatography (CH2Cl2: MeOH 200:1~50:1) to give 18b(61.00 mg, 62.1%) as a white solid: mp 142-144 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 2h;Inert atmosphere; | Synthesis of 5-(5-cyanopyridin-3-yI)thiophene-2-carboxylic acid (All)(5-Cyanopyridin-3-yl)boronic acid pinacol ester (0.720 g, 3.13 mmol), 5-bromoth iophene-2-carboxylic acid(0.589 g, 2.84 mmol) and Na2CO3 (0.905 g, 8.53 mmol) were mixed in DME (30 mL) and water (7.5 mL)and degassed with Ar. Then PdCI2(dppf) (0.100 g, 0.142 mmol) was added and the mixture was stirred at100 C for 2 h. The reaction was allowed to cool to RT. Water (30 mL) was added to redissolve theproduct and the mixture was filtered over Celite to remove the undissolved palladium. The mother liquor was acidified with 1 N aqueous HCI to pH 1.9-2.0. Solids were filtered off and washed with water (3x 10 mL). The solid was suspended in water and lyophilization (MeCN/H20) afforded 5-(5-cyanopyridin-3- yl)thiophene-2-carboxylic acid (All, 0.374 g, 1.62 mmol, 57%) as an off-white solid. LCMS: calc. for= 252.05, found 252.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With potassium carbonate; In 1,4-dioxane; at 95℃; for 4h;Inert atmosphere; Sealed tube; | A mixture consisting of 6-bromo-N-(3-chlorophenyl)quinazolin-4-amine - HC1 (500 mg 1.49 mmol), 5 -(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)nicotinonitrile (286 mg, 1.24 mmol) and 2.OM K2C03 (3.1 mL) in 15 mL of 1,4-dioxane was degassed (vacuum/nitrogen, 3 times). To the reaction mixture was added SiliCat DPP-Pd (70 mg, 0.26 mmol/g loading). The reaction mixture was sealed and heated at 95 C for 4 hous. The reaction mixture was cooled and filtered througha glass frit. The solids were washed with ethanol. The filtrate was concentrated under reduced pressure. Toluene was added to the residue and concentrated under reduced pressure. The residue was chromatographed on a 40 g silica column using the dry loading method and eluted with a gradient of 25:75 to 95:5 ethyl acetate-dichloromethane followed by the addition of 5% methanol up to 9% methanol in the 95:5 ethyl acetate-dichloromethane system to give 147 mg(33%) of the title compound as a pale yellow solid; MS (ES-API+) m/z 358.0 (M+1), 360.0 (Cl isotope), (ES-API-) m/z 356.0 (M-1), 358.0 (Cl isotope); ?H NMR (400 MHz, DMSO-d6) oe 9.95 (s, 1H), 9.41 (d, J=2.20 Hz, 1H), 9.08 (d, J1.83 Hz, 1H), 8.94 (d, J1.74 Hz, 1H), 8.82 (t, J=2.10 Hz, 1H), 8.69 (s, 1H), 8.34 (dd, J1.83, 8.69 Hz, 1H), 8.07 (t, J1.97 Hz, 1H), 7.92 (d, J=8.69 Hz, 1H), 7.84 (dd, J=1. 19, 8.23 Hz, 1H), 7.44 (t, J=8. 14Hz, 1H), 7.20 (dd, J1.33, 7.91Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | 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), 5-cyanopyridin-3-ylboronic acid pinacol ester (27 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.1 N HCl (1 mL) was added followed by water (5 mL) and the mixture was extracted with EtOAc (3x5 mL). The combined organic layers were dried with sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by semi-prep HPLC-MS (column X-Bridge 30x50) using a solution of MeCN in water (containing 10 mM of NH4CO2H) (35 to 55%). The product was lyophylised and afforded the title compound (8.6 mg, 0.016 mmol, 17%) as a white solid. 1H NMR (500 MHz, DMSO) delta 8.97 (d, J = 1.7 Hz, 1H), 8.89 (d, J = 2.1 Hz, 1H), 8.41 (t, J = 2.0 Hz, 1H), 8.12 (d, J = 2.0 Hz, 1H), 7.94 (dd, J = 8.5, 2.0 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 3.33 (1H, below water signal), 2.26 (s, 3H), 1.17 (d, J = 6.7 Hz, 6H); MS (m/z): 530.0 [M+H]+. |
17% | With tetrakis(triphenylphosphine) palladium(0); water; 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), 5-cyanopyridin-3-ylboronic acid pinacol ester (27 mg, 0.12 mmol), Pd(PPh3)4 (11 mg, 0.10 mmol), Na2CO3 (51 mg, 0.48 mmol) in degassed 1,4-dioxane and H20 (4:1, 1.9 mL) was heated at 85 C for 18 hours. 1 N HCI (1 mL) was added followed by water (5 mL) and the mixture was extracted with EtOAc (3x5 mL). The combined organic layers were dried with sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by semi-prep HPLC-MS (column X-Bridge 30x50) using a solution of MeCN in water (containing 10 mM of NH4CO2H) (35 to 55%). The product was lyophylised and afforded the title compound (8.6 mg, 0.016mmol, 17%) as a white solid. 1H NMR (500 MHz, DMSO) O 8.97 (d, J= 1.7 Hz, 1H), 8.89 (d, J= 2.1 Hz, 1H),8.41 (t, J= 2.0 Hz, 1H), 8.12 (d, J= 2.0 Hz, 1H), 7.94 (dd, J= 8.5, 2.0 Hz, 1H), 7.70 (d, J=8.5 Hz, 1H), 3.33 (1H, below water signal), 2.26 (5, 3H), 1.17 (d, J= 6.7 Hz, 6H); MS (mlz):530.0 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With hydrazine hydrate; caesium carbonate; In water; at 120℃; for 16h; | 25 mL of the reaction flask was added hydrazine hydrate (0.25 mmol)5-Cyano-pyridine-3-boronic acid pinacol ester (0.5mmol),Cesium carbonate (1.0 mmol),Water (2.5 mmol)And polyethylene glycol-2000 (2.0 g).The reaction mixture was reacted at 120 C until the reaction was complete.The reaction mixture was cooled to room temperature,The product was isolated by column chromatography after evaporation of the solvent under reduced pressure,Yield 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(triphenylphosphine)palladium(II) dichloride; potassium carbonate; triphenylphosphine; In propan-1-ol; water; at 100℃; for 1h;Inert atmosphere; | N-(4-Bromo-3-[(d imethylami no)methylidene]su lfamoyl}phenyl)-2-(2-ch lorophenyl)acetamide (250 mg, 545 pmol) and 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridine-3- carbonitrile (125 mg, 545 pmol) were dissolved in n-propanol (10 ml) andbis(triphenylphosphine)palladium(l I) dichloride (CAS 13965-03-2) (19.2 mg, 27.2 pmol) and triphenylphosphine (7.15 mg, 27.2 pmol) were added. The solution was purged with argon for 5 minutes and aq. potassium carbonate (1.6 ml, 1.0 M, 1.6 mmol) was added. The reaction was heated at 100C for lh. Afterwards the mixture was filtered over Celite, the solvent was removed under reduced pressure and ethyl acetate and water wereadded. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over Whatmanfilter and the solvent was removed under reduced pressure.The crude was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 1h;Inert atmosphere; | To a 20 mL vial was added (((2,2?-dimethyl-[1,1?-biphenylj-3,3?-diyl)bis(methylene))bis(oxy))bis(6-formyl-3, 1 -phenylene) bis(trifluoromethanesulfonate) (279 mg, 0.34mmol), <strong>[402718-29-0]5 -(4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)nicotinonitrile</strong> (188 mg, 0.82 mmol, 2.4 equiv),[1,1?-Bis(diphenylphosphino)ferrocenejdichloropalladium(II) (26 mg, 0.03 mmol, 10 mol%), potassium carbonate (113 mg, 0.82 mmol, 2.0 equiv), N,N-dimethylformamide (3.4 mL, 0.1M), and water (0.4 mL) at room temperature. The vessel was sealed, and the mixture was sparged with nitrogen for 5 minutes before being heated to 90 C for 1 hour. The reaction mixture was then cooled to room temperature,ethyl acetate (10 mL) was added, and the contents of the vial were filtered through celite. The filtrate was diluted with ethyl acetate (50 mL) and washed once with water and once with brine. The organic layer was then dried over magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel column chromatography using a 0-10% methanol in methylene chloride eluent gradient to provide 5,5 ?-((((2,2?-dimethyl- [1,1 ?-biphenylj-3 ,3 diyl)bis(methylene))bis(oxy))bis(6-formyl-3, 1 -phenylene))dinicotinonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | 100 g of intermediate 1-1, 186 g of intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added to a 2 L three-necked flask, and 800 ml of toluene, 200 ml of ethanol, and 200 ml of water were sequentially added. Nitrogen gas was introduced, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 °C for refluxing for 8 h. TLC was used to monitor the reaction of the starting material to room temperature and filtered to remove insoluble.The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to obtain 104.5 g of intermediate 1 in a yield of 89.3percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.2% | 100 g of intermediate 2-1, 186 g of intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added to a 2 L three-necked flask, and 800 ml of toluene, 200 ml of ethanol, and 200 ml of water were successively added. Nitrogen gas was added, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 C for refluxing for 8 hours. The TLC was used to monitor the reaction of the starting materials and then cooled to room temperature.The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to obtain 107.9 g of intermediate 2 in a yield of 92.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.8% | In a 2 L three-necked flask, 100 g of Intermediate 3-1, 186 g of Intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added, followed by 800 ml of toluene, 200 ml of ethanol, 200 ml of water, Nitrogen gas was introduced, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 C for refluxing for 8 h. TLC was used to monitor the reaction of the starting material to room temperature and filtered to remove insoluble. The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to afford 101.6 g of Intermediate 3. The yield was 86.8%. |
Tags: 402718-29-0 synthesis path| 402718-29-0 SDS| 402718-29-0 COA| 402718-29-0 purity| 402718-29-0 application| 402718-29-0 NMR| 402718-29-0 COA| 402718-29-0 structure
[ 1346809-48-0 ]
2-(Methylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile
Similarity: 0.89
[ 848093-29-8 ]
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde
Similarity: 0.87
[ 1171891-31-8 ]
4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.86
[ 329214-79-1 ]
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.84
[ 1012084-56-8 ]
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.80
[ 1346809-48-0 ]
2-(Methylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile
Similarity: 0.89
[ 741709-62-6 ]
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile
Similarity: 0.79
[ 878194-92-4 ]
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile
Similarity: 0.77
[ 1220219-59-9 ]
3-Methyl-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzonitrile
Similarity: 0.72
[ 214360-46-0 ]
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
Similarity: 0.72
[ 1346809-48-0 ]
2-(Methylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile
Similarity: 0.89
[ 848093-29-8 ]
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde
Similarity: 0.87
[ 1171891-31-8 ]
4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.86
[ 329214-79-1 ]
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.84
[ 1012084-56-8 ]
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
Similarity: 0.80
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
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 |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :