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CAS No. : | 833486-94-5 | MDL No. : | MFCD06795680 |
Formula : | C12H17BN2O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QOYJKGGBFKVKDP-UHFFFAOYSA-N |
M.W : | 264.09 | Pubchem ID : | 16217914 |
Synonyms : |
|
Num. heavy atoms : | 19 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.5 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 76.14 |
TPSA : | 90.3 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -6.06 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 2.61 |
Log Po/w (WLOGP) : | 1.48 |
Log Po/w (MLOGP) : | 0.1 |
Log Po/w (SILICOS-IT) : | -1.05 |
Consensus Log Po/w : | 0.63 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.22 |
Solubility : | 0.158 mg/ml ; 0.000598 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.16 |
Solubility : | 0.0184 mg/ml ; 0.0000698 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -3.02 |
Solubility : | 0.252 mg/ml ; 0.000955 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 4.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 3.14 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium acetate;palladium diacetate; In N,N-dimethyl-formamide; at 85℃; for 5h; | Example 5; N-(5-{2-[(2-Chlorophenyl)amino]-6-oxo-1,6-dihydro-4-pyrimidinyl}-1H-benzimidazol-2-yl)-2-thiophenecarboxamide (Ie); a. 2-Nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (VI) To a solution of 4-bromo-2-nitroaniline (10.0 g, 46.0 mmol), bis(pinacolato)diboron (12.8 g, 50.6 mmol) and potassium acetate (13.5 g, 138.0 mmol) in DMF (175 mL), palladium(II) acetate (309.8 mg, 1.38 mmol) was added and stirred at 85 C. for 5 hrs under argon. The mixture was concentrated, water was poured into it and extracted with CH2Cl2. The organic extract was dried over Na2SO4, and then concentrated. Recrystallizations from CH2Cl2/hexane gave the title compound (16.1 g, 92%). 1H-NMR (400 MHz, d6-DMSO) delta 8.27 (s, 1H), 7.70 (s, 2H), 7.55 (d, 1H), 6.98 (d, 1H) and 1.27 (s, 12H). |
91.9% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; for 2h;Inert atmosphere; | Dissolve 4-bromo-2-nitroaniline (10.85 g, 50 mmol) in 150 mL of 1,4-dioxane,JoiningPinacol diborate (25.4g, 100mmol), potassium acetate (14.7g, 150mmol), the reaction was heated to 100 C in an argon atmosphere, and then [1,1'-bis (diphenylphosphino) di Ferrocene] palladium dichloride (1.83 g, 2.5 mmol), and the reaction was continued for 2 hours. After cooling to room temperature, the solvent was removed by rotary evaporation under reduced pressure, and the product was quickly separated and purified by using column chromatography (dichloromethane as eluent) to obtain a yellow solid, 12.13 g, yield 91.9%. |
86% | With potassium acetate;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 85℃; | Nitro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)anilineTo a solution of 4-bromo-2-nitrobenzenamine (4 g, 18.43 mmol) in 1 ,4-dioxane (100 mL) was added KOAc (5.4 g, 55.02 mmol), Pd(dppf)Cl2 (405 mg, 0.55 mmol), dppf (307 mg, 0.55 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l ,3,2-dioxaborolane (5.15 g, 20.28 mmol). The resulting solution was stirred overnight at 85C. Then the reaction was quenched by the addition of water (200 mL), extracted with ethyl acetate (3 x 80 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum to give a residue, which was purified via silica gel chromatography (petroleum ether) to afford 2-nitro-4-(4,4,5,5- tetramethyl- l ,3,2-dioxaborolan-2-yl)aniline as a yellow solid (4.2 g, 86%).'H-NMR (300 MHz, CDC13) delta 8.60 (d, J = 0.9 Hz, 1H), 7.72 - 7.75 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.24 (s, 2H), 1.35 (s, 12H) |
80% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere; | To a reaction vesse containing 4-bromo-2-nitroaniHne (150 g, 693 mmo) and bis(pinacoato) diboron (352 g,1.39 mo) in DMF (1.5 L) were added Pd(dppf)C2 (5.07g, 6.93 mmo) and potassiumacetate (34.1 g, 3.47 nio) sequentiaHy. The reaction mixture was heated at 80 C under anN2 atmosphere for 18 h. After cooHng to rt, water (7.5 L) and EtOAc (1.8 L) were added.The ayers were separated, and the aqueous ayer was extracted with EtOAc (900 mL).The combined organic ayers were washed with brine (6 L), dried over Na2SO4, and concentrated n vacuo. The crude product was surhed wfth methano (900 mL) and ifitered to provide the desired product as a yeflow powder (147g, 80% yed), 1H NMR (400 MHz, CDC3) 5 8.61 (d, J = 1.2 Hz, I H), 775 (dd, J = 8.4 Hz, 1.2 Hz, I H), 6.79 (d, J = 8.4 Hz, IH), 6.22 (bs, 2H), 1.35 (s, 12H). |
77% | With trans-bis(triphenylphosphine)palladium dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 5h; | 30 g of 4-bromo-2-nitroaniline (138 mmol), 42 g of bis(pinacolato)diborane (166 mmol), 4.9 g of bis(triphenylphosphine)palladium(II) (6.9 mmol), 34 g of potassium acetate (345 mmol), and 690 mL of 1,4-dioxane were introduced into a reaction vessel, and the mixture was stuffed at 120C for 5 hours. After completion of the reaction, the mixture was washed with distilled water, extracted with ethyl acetate, and the extracted organic layer was dried with magnesium sulfate. The solvent was removed with a rotary evaporator, and the resulting product was purified by column chromatography to obtain 28 g of compound 1-3 (yield: 77%). |
75% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; | Part C: Preparation of 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine A mixture of 4-bromo-2-nitro-aniline (217 mg, 1 mmol), bis(pinacolato)diboron (279 mg, 1.1 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (25 mg, 0.03 mmol) and potassium acetate (294 mg, 3 mmol) in methyl sulfoxide (4 mL) was heated under N2 at 80 C. overnight. The crude reaction mixture was filtered through Celite and then partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium bicarbonate (*3), dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica gel, 20% ethyl acetate/hexane) gave the desired product as a yellow solid (198 mg, 75% yield). |
56% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 20 - 80℃; for 24h;Inert atmosphere; | A 100 mL three necked flamed dried round bottomed flask was charged with 30 mL of dry DMF (30 mL) under argon. The flask was then degassed with argon for 30 minutes using a gas dispersion tube. Once this was achieved, 4- bromo-2-nitrophenylamine(44)(1 g, 0.0046 mol), pinacolborane dimer (45)(1.28 g, 0.0051 mol), and potassium acetate (1.35 g, 0.0138 mol) were added. The resulting mixture was stirred at room temperature under argon for five minutes. After this time, 1 '- 5/'s(diphenylphosphino)ferrocene]dichloropalladium(ll) (0.37 g, 0.00046 mol) was added, upon which the mixture turned black. The mixture was then heated at 80 C for 24 hours under argon. After this time, the reaction mixture was added to water (300 mL) and extracted with ethyl acetate (3 chi 30 mL). The combined organics were washed with water (3 chi 30 mL), brine (3 chi 30 mL), and dried (MgS04). The organic layer was removed under reduced pressure to afford a yellow solid, which was purified by column chromatography on silica, eluting with ethyl acetate / petroleum ether (1 : 1), to afford the title compound (46) as a deep yellow solid. (0.68 g, 56 %); mp 172 C; Rf = 0.45 (ethyl acetate : petroleum ether, 1 : 1 ; vmax (KBr) / cm"1 3471 (NH2), 3329 (NH2), 2980 (CH), 1553 (N02), 1342 (N02); deltaEta (d6-DMSO, 300 MHz) 8.28 (1 H, d, 3, 5= 1.2, H3), 7.67 (2H, s, NH2), 7.57 (1 H, dd, J5, 6= 8.4, J5, 3= 1.2, H5), 7.00 (1 H, d, J6, 5= 8.4, H6), 1.29 (12H, s, 4 CH3); (d6-DMSO, 75 MHz) 148.5 (d), 140.6 (C5), 133.2 (C3), 130.7 (C2), 119.2 (C6), 84.1 (2 C(CH3)2), 25.1 (4 CH3). |
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 100℃; for 0.75h; | A mixture of 4-bromo-2-nitrophenylamine (1 g), bis(pinacolato)diboron (2.35 g), potassium acetate (2.3 g) and dichloro(1,1'-bis(diphenylphosphino)ferrocene) palladium(II).dichloromethane (0.10 g) in DMF (9.2 mL) was stirred at 100 C. for 45 minutes. The reaction was filtered through diatomaceous earth (Celite). The filtrate washed with water and brine and dried (Na2SO4) filtered and concentrated. The concentrate was purified on silica with an Intelliflash-280 purification system with ethyl acetate/hexanes. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 18h; | In a 1 L round-bottomed flask was charged 4-bromo-2-nitroaniline (25.69 g, 118 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (60.1 g, 237 mmol), potassium acetate (58.1 g, 592 mmol), and [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf)) (0.199 g, 0.272 mmol) in N,N-dimethylformamide (237 ml). The mixture was heated at 100 0C for 18 hours. The mixture was cooled to ambient temperature, filtered through a pad of silica gel, and rinsed with ethyl acetate (500 mL). The filtrate was washed with brine (4 x 200 mL), dried over MgSO4, and concentrated. The concentrate was treated with 300 mL hexanes and 150 mL methanol and was heated at 60 0C to get most of the slurry to dissolve. The reaction was allowed to cool to ambient temperature and was then allowed to stand in the freezer for 2 days. The suspension was filtered, rinsed with cold hexanes, and dried to constant weight to provide the title compound. MS DCI+) m/e 265.1 (M+H)+. | |
With 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃;Inert atmosphere; | A 100 ml. round-bottomed flask was charged with 4, 4, 5, 5, 4', 4', 5', 5'- octamethyl-[2,2']bi[[1 ,3,2]dioxaborolanyl] (3.86 g, 0.0152 mol), PdCI2dppf (303 mg, 0.415 mmol), KOAc (4.07 g, 0.0415 mol), and dppf (230 mg, 0.415 mmol), was flushed with Argon, treated with a solution of 4-bromo-2-nitro-phenylamine (3.00 g, 0.0138 mol) in anhydrous dioxane (30 ml_), and heated to 1000C overnight. The cooled mixture was filtered through a frit, and the solid was washed with EtOAc. The filtrate was diluted with 200 ml. EtOAc and washed twice with 150 ml. brine. The combined aqueous layers were extracted four times with 100 ml. EtOAc. The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 200-g Sepra Si 50 SPE column (Isco system: flow rate = 40 mL/min; eluting with EtOAc/hexane, 10:90, v/v over 15 min and 10:90 to 40:60, v/v over 25 min).The chromatography was repeated as above to yield 2-Nitro-4-(4, 4,5,5- tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-phenylamine as a bright yellow solid.1H-NMR (400 MHz; CDCI3) delta: 8.59 (s, 1 H), 7.72 (d, J = 8.6 Hz, 1 H), 6.77 (d, J = 8.3 Hz, 1 H), 6.20 (br. s., 2H), 1.33 (s, 12H). Mass Spectrum (LCMS,ESI pos.) Calcd. For Ci2H17BN2O4: 265.1 (M + H), Found 265.1. | |
With potassium acetate; palladium diacetate; In N,N-dimethyl-formamide; at 85℃; for 20h;Inert atmosphere; | Step A: 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine (1199) Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of argon, was placed a solution of 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (25.70 g, 101.00 mmol), 4-bromo-2-nitroaniline (20.00 g, 92.00 mmol) and potassium acetate (27.10 g, 276.00 mmol) in DMF (250 mL). This was followed by the addition of PdOAc2 (0.62 g, 2.76 mmol) at ambient temperature. The resulting mixture was stirred at 85 C. for 20 hr under argon and then it was cool down to 20 C., quenched with water (200 mL) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with EA in PE (50%) to afford the crude product. The crude was recrystallized from PE/EtOAc (200 mL/10 mL) and dried over in vacuum to afford the title compound: LCMS (ESI) calc'd for C12H12BN2O4 [M+H]+: 265. found 265. 1H NMR (400 MHz, DMSO-d6): delta 8.26 (s, 1H), 7.70 (s, 2H), 7.55 (d, J=8.4 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 1.27 (s, 12H). | |
With potassium acetate; palladium diacetate; In N,N-dimethyl-formamide; at 20 - 85℃; for 20h;Inert atmosphere; | Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of argon, was placed a solution of 4,4,4?,4?,5 ,5 ,5 ?,5 ?-octamethyl-2,2?-bi( 1,3,2- dioxaborolane) (25.70 g, 101.00 mmol) , 4-bromo-2-nitroaniline (20.00 g, 92.00 mmol) and potassium acetate (27.10 g, 276.00 mmol) in DMF (250 mL). This was followed by the addition of PdOAc2 (0.62 g, 2.76 mmol) at ambient temperature. The resulting mixture was stirred at 85C for 20 hrunder argon. The reaction mixture was allowed to cool to 20C, quenched with water (200 mL) and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with EA in PE (50%) to afford the crude product. The crude was recrystallized from PE/EA (200 mL/10 mL), the solid was collected by filtration and dried over in vacuum to afford the title compound as a solid: LCMS (ESI) calc?d for C,2H,7BN204[M + H]: 265, found 265; ?H NMR (400 MHz, DMSO-d6): oe 8.26 (s, 1H), 7.70 (s, 2H), 7.55 (d, J= 8.4 Hz, 1H) , 6.97 (d, J= 8.4 Hz, 1H), 1.27 (s, 12H). | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 2h;Inert atmosphere; | solution of the 4-bromo-2-nitroaniline (1.63 g, 7.5 mmol),KOAc (2.21 g, 22.5 mmol), bis(pinacolato)diborane (3.81 g,15 mmol) and Pd(dppf)Cl2 (0.28 g, 0.38 mmol) in anhydrous 1,4-dioxane (30 mL) under argon was stirred at 100 C for 2 h. 1,4-dioxane was removed under reduced pressure and add water(100 mL), extracted with ethyl acetate (3 x 100 mL), the organiclayer was washed with water (2 x 100 mL), dried with Na2SO4 andevaporated to give as a yellow solid and used for next step withoutanother purification (>90% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 80℃; | Part D: Preparation of tert-butyl 4-(4-amino-3-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate A mixture of <strong>[833486-94-5]2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine</strong> (27 mg, 0.1 mmol), tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (36 mg, 0.11 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (4.9 mg, 0.006 mmol) and potassium carbonate (31 mg, 0.23 mmol) in DMF (2 mL) was heated at 80 C. overnight. The crude reaction mixture was filtered through Celite and then partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with saturated sodium bicarbonate (*3), dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica gel, 5% ethyl acetate/hexane) gave the desired product (17.2 mg, 54% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In methanol; dichloromethane; at 20℃; | 2-Nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g) was stirred under hydrogen balloon with palladium on carbon (10%, 150 mg) in a mixture of MeOH and DCM (1:1, 10 ml) at room temperature overnight. The reaction mixture was then filtered through Celite, volatiles removed in vacuo, and the residue purified by flash chromatography to give 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamine (890 mg). | |
With hydrogen;palladium 10% on activated carbon; In methanol; under 2475.25 Torr; for 2h; | Step 1. (A)5-(4,4,5,5-tetramethyI-l,3»2-dioxaborola?-2-yl)-lH-benzo[d]imidazoI-2(3H)-one [00245] To a solution of commercially available 2-nitro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)aniline (2.0 g, 7.5 mmol) in MeOH (50 mL) was added 10% wet Pd-C (50% water in weight, 200 mg). The reaction mixture was flushed with H2 and hydrogenated at 3.3 bar for 2 h. Upon completion the suspension was filtered through Celite to remove the catalyst. The filtrate was concentrated under reduced pressure to give 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)benzene-l,2-diamine, that was submitted to the next step without further purification. | |
With hydrogen;palladium 10% on activated carbon; In ethyl acetate; at 20℃; under 3102.97 Torr; for 18h; | EXAMPLE 2A (5 g, 18.5 mmol) was dissolved into 100 mL of EtOAc, treated with 10% Pd/C (2 g, 1.89 mmol). The mixture was place in a Parr hydrogenation apparatus under 60 psi of H2 at RT for 18 hr. The reaction was filtered, and reduced in vacuo. The product was triturated with Et2O/hexanes, and carried on without further purification. |
With hydrogen;palladium 10% on activated carbon; In ethyl acetate; at 20℃; under 1551.49 Torr; for 36h; | In a 250 niL stainless steel pressure bottle a solution of EXAMPLE IH (5 g, 18.93 mmol) in ethyl acetate (50 rnL) was treated with 10% Pd on carbon (1.25 g, 1.175 mmol). The suspension was stirred under a hydrogen atmosphere for 36 hours at 30 psi at ambient temperature. The mixture was filtered through a nylon membrane and concentrated to provide the title compound. MS APCI(+)) m/e 235.19 (M+H)+. | |
With platinum(IV) oxide; hydrogen; In ethyl acetate; | Step A: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamine. A solution of <strong>[833486-94-5]2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (4.5 g, 17 mmol) in EtOAc (360 mL) was hydrogenated in a Continuous-flow Hydrogenation Reactor (H-cube) (1.5 mL/min, 70 mm/30 mm PtO210% cartridge, full H2 mode, 1 cycle). The solution was concentrated in vacuo afford the title compound as a clear oil which was in the next step without further purification. | |
With palladium 10% on activated carbon; hydrogen; In methanol; dichloromethane; at 20℃; for 16h; | Step B: 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamine (1200) Into a 250-mL round-bottom flask, was placed a solution of <strong>[833486-94-5]2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (7.40 g, 25.20 mmol) in MeOH (50 mL) and DCM (50 mL). This was followed by the additional of Pd/C (134 g, 126 mmol, wet 10%) at ambient temperature. The reaction mixture was degassed with nitrogen for 3 times and stirred under hydrogen for 16 hr at ambient temperature. The resulting mixture was filtered and the filter cake was washed with DCM (3×10 mL). The combined organic layers were concentrated in vacuo and purified by silica gel column chromatography, eluted with EA in PE (30%) to afford the title compound: LCMS (ESI) calc'd for C12H19BN2O2 [M+H]+: 235. found 235. 1H NMR (400 MHz, CD3C1): delta 7.23 (d, J=7.6 Hz, 1H), 7.17 (s, 1H), 6.70 (d, J=8.0 Hz, 1H), 3.19 (br, 4H), 1.32 (s, 12H). | |
With palladium 10% on activated carbon; hydrogen; In methanol; dichloromethane; at 20℃; for 16h; | Into a 250-mL round-bottom flask, was placed a solution of 2-nitro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (7.40 g, 25.20 mmol) in MeOH (50 mL) and DCM (50 mL). This was followed by the addition of Pd/C (134 g, 126 mmol, wet 10%) at ambient temperature. The reaction mixture was degassed with nitrogen for 3 times and stirred under hydrogen for 16 hrat ambient temperature. The mixture was filtered. The filter cake was washed with DCM (3 x 10 mL). The combined organic layers were concentrated under reduced pressure and purified by silica gel column chromatography, eluted with EA in PE (30%) to afford the title compound as a solid: LCMS (ESI) calc?d for C,2H,9BN202[M + H]: 235, found 235; ?H NMR (400 MHz, CD3C1): oe 7.23 (d, J= 7.6 Hz, 1H), 7.17 (s, 1H), 6.70 (d, J= 8.0 Hz, 1H) , 3.19 (br, 4H), 1.32 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; at 130℃; for 0.333333h;microwave irradiation; | A mixture of EXAMPLE 174A (0.3 g, 0.6 mmol), EXAMPLE 2A (0.32 g, 1.24 mmol) (Ph3P)2PdCl2 (0.021 g, 0.03 mmol), and 2 M aqueous Na2CO3 (0.62 mL, 1.24 mmol). The slurry was heated to 130 C. for 20 min in a microwave reactor. The reaction was filtered over a pad of Celite, washed with CH2Cl2. The organics were reduced in vacuo directly onto silica. The reaction was purified via an Intelliflash-280 purification system (CH2Cl2/MeOH/NH4OH) to afford the desired trans-diastereomeric product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; at 130℃; for 0.25h;microwave irradiation; | A mixture of EXAMPLE 2A (0.21 g), cis-4-(4-(4-amino-3-iodopyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)-1-methylpiperazin-2-one, prepared as described in WO 05/074603, (0.18 g) 2M Na2CO3 (0.38 mL), and dichlorobis(triphenylphosphine) palladium(II) (0.014 g) in DME/water (3 mL/1 mL) in microwave reactor was stirred at 130 C. for 15 minutes. The mixture was filtered through diatomaceous earth (Celite) and dried (Na2SO4), filtered and concentrated. The concentrate was purified on silica gel with an Intelliflash-280 purification system with dichloromethane/methanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 35; 5-[1-(1-Benzyl-piperidin-4-yl)-4-morpholin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-1,3-dihydro-benzoimidazol-2-one (Scheme 33)53 mg (0.2 mmol) 4-amino-3-nitrophenylboronic acid, pinacol ester was suspended in 2 mL DME. A catalytic amount of Pd/C was added and the nitro group was reduced under an atmosphere of hydrogen over 4 days. 130 uL Net3 was added followed by 30 mg triphosgene. The mixture was stirred for 15 min and 50 mg 1-(1-Benzyl-piperidin-4-yl)-6-chloro-4-morpholin-4-yl-1H-pyrazolo[3,4-d]pyrimidine was added, followed by 250 uL of a 2M solution of Na2CO3 and 10 mol % Pd(PPh3)4. The mixture was heated under microwave irradiation at 185 C for 6 min. The solvents were evaporated and the mixture was purified by HPLC (TFA buffers). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; methanol; at 80℃;Inert atmosphere; | b)Under argon, a solution of methyl [[(2-halogeno-4-methyl-1,3-thiazol-5-yl)carbonyl](pyridin-2-ylmethyl)amino]acetate (159 mg of the mixture of 2-chloro and 2-bromo compounds obtained above), <strong>[833486-94-5]2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (234 mg, 0.86 mmol), cesium carbonate (280 mg, 0.86 mmol), and tetrakis(triphenylphosphine)palladium (17.4 mg, 0.015 mmol) in degassed 1,4-dioxane (4 mL) and methanol (0.2 mL) was stirred at 80 C. overnight. The reaction mixture was filtered through a bed of celite and rinsed with dichloromethane, methanol and ethyl acetate. The solvents were evaporated and the crude product was purified by flash chromatography (silica gel, dichloromethane/methanol 9/1) to give methyl [[2-(4-amino-3-nitrophenyl)-4-methyl-1,3-thiazol-5-yl]carbonyl}(pyridin-2-ylmethyl)amino]acetate (100 mg). The latter compound was dissolved in tetrahydrofuran (1 mL) and water (1 mL), lithium hydroxide (100 mg, 4.1 mmol) was added and the resulting mixture was stirred at room temperature overnight. An aqueous hydrochloric solution (1N) was added and the reaction mixture was extracted with diethyl ether, ethyl acetate, and dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated. Crystallization in a mixture of ethyl acetate, cyclohexane, dichloromethane and methanol afforded [[2-(4-amino-3-nitrophenyl)-4-methyl-1,3-thiazol-5-yl]carbonyl}(pyridin-2-ylmethyl)amino]acetic acid (40 mg, 15% from 2-bromo-4-methyl-1,3-thiazole-5-carboxylic acid) as a red solid.ESI-MS m/z 428 (M+H)+.1H NMR (CD3OD), delta (ppm): 8.58-8.53 (m, 2H), 7.86-7.82 (m, 2H), 7.40-7.35 (m, 2H), 7.02 (d, J=8.2 Hz, 1H), 4.29-4.24 (m, 2H), 2.44 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; at 90℃; for 24h;Inert atmosphere; | Example 43-[5-(2-Fluoro-6-trifluoromethoxy-phenyl)-lH-benzimidazol-2-yl]-l-oxa-2- aza-spiro [4.5] dec-2-ene hydrochloride (Cpd 8)A. 2'-Fluoro-3-nitro-6'-trifluoromethoxy-biphenyl-4-ylamine 2-Fluoro-l-iodo-6-trifluoromethoxybenzene (612 mg, 2.00 mmol, prepared as described in WO2005/097136), <strong>[833486-94-5]4-amino-3-nitrophenylboronic acid pinacol ester</strong> (1.3 eq., 687 mg, 2.60 mmol), and (dppf)PdCl2-DCM (0.05 eq., 81.6 mg, 0.100 mmol) were placed in a 40 mL vial equipped with a magnetic stir bar. The vial was evacuated and backflushed with Ar, and DME (10 mL) and 2M aq Na2COs (4 mL) were added via syringe. The vial was capped tightly and placed in a heating block where the reaction was stirred at 90 0C for 24 h. The reaction was cooled to room temperature, diluted with EtOAc, and washed sequentially with water and brine. The organic extract was dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography using an 80-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0: 1 to 2:3, v/v over 30 min, yielding 548 mg (87 %) of the desired compound. 1H-NMR (400 MHz, CDCl3) delta: 8.21 (s, IH), 7.30 - 7.47 (m, 2H), 7.18 (d, J = 8.1 Hz, IH), 7.14 (t, J = 8.6 Hz, IH), 6.91 (d, J = 6.6 Hz, IH), 5.37 (br. s., 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 65℃; for 6h;Inert atmosphere; | 4-Amino-3-nitrophenylboronic acid pinacol ester (1.60 g, 6.06 mmol), 3-bromopyridine (1.10 g, 6.96 mmol), cesium carbonate (3.33 g, 10.22 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride DCM complex (491 mg, 0.60 mmol) were suspended in dimethylformamide (20 mL). The solution was degassed by vacuum several times and placed in an argon atmosphere. It was then heated to 65 C. for 6 hr. After cooling, EA (100 mL) and water (40 mL) were added. When additional water (50 mL) was added to the organic layer, a precipitate was formed in the separatory funnel. The biphasic solution was filtered, and the filtrate was transferred to the separatory funnel and separated. The organic phase was washed twice with water (50 mL each), then with brine, and then dried with sodium sulfate and concentrated under reduced pressure to give 2-nitro-4-(pyridin-3-yl)benzenamine (1.18 g). 2-Nitro-4-(pyridin-3-yl)benzenamine (700 mg, 3.26 mmol) in 1:1 ethanol/EA (40 mL) was hydrogenated at atmospheric pressure with 10% palladium on carbon (90 mg, 0.08 mmol) at room temperature for 2 days. Filtration and concentration under reduced pressure gave 4-(pyridin-3-yl)-benzene-1,2-diamine (621 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 4h; | 5-Bromo-furan-2-carboxylic acid ((S)-cyclohexyl-methylcarbamoyl-methyl)-amide (0.50 g, 1.46 mmol), <strong>[833486-94-5]4-amino-3-nitrophenylboronic acid pinacol ester</strong> (0.54 g, 2.04 mmol) and tetrakis(triphenylphosphine)palladium (0.17g, 0.15 mmol) are dissolved in DME (50 mL). A 2M sodium carbonate solution (2.9 mL, 5.83 mmol) is added and the resulting solution is degassed with Argon during 5 min. The solution is heated to reflux (100 0C) for 4h under Argon. Upon cooling the resulting mixture is diluted with EtOAc/H2O and the aqueous phase is extracted with EtOAc. The yellow product is precipitating out of the organic layer and is filtered off. The product is washed with EtOAc and dried in vacuum. 493 mg, 85% LC/MS ESI m/z (M+H)+ = 401.42. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;palladium diacetate; CyJohnPhos; In 1,2-dimethoxyethane; water; at 130℃;Inert atmosphere; microwave irradiation; | 4-Bromo-Lambda/-methyl-2-nitroaniline (100mg, 0.43mmol), 2-nitro-4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)aniline (115mg, 0.43mmol), biphenyl-2-yldicyclohexylphosphine (30mg, 20mol%) and K3PO4 (275mg, 1.3mmol) were suspended in DME-H2O (4:1 , 5ml_). the mixture was purged with nitrogen then degassed by sonication. Pd(OAc)2 (5mg, 5mol%) was added, and the mixture heated to 13O0C for 10min under microwave irradiation. The cooled mixture was diluted with EtOAc and H2O. The organics were separated and the aqueous layer extracted with EtOAc (3x50ml_). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give the crude product as a dark brown solid (210mg). The crude material was taken on without further purification.1H NMR (DMSO): 8.29-8.14 (3 H, m), 7.90 (1 H, dd, J 9.1 and 2.3), 7.77 (1 H, td, J 8.5 and 2.3), 7.54 (2 H, br s), 7.15-7.05 (2 H, m) and 3.00 (3 H, d, J 5.0). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 130℃;Inert atmosphere; microwave irradiation; | 4-Bromo-2-fluoro-1 -nitrobenzene (500mg, 2.27mmol), 2-nitro-4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)aniline (660mg, 2.50mmol) and K2CO2 (940mg, 6.81 mmol) were suspended in DME-H2O (4:1 , 15mL) and purged with nitrogen. The solution was degassed by sonication before Pd(dppf)CI2 (185mg, 10mol%) was added. The mixture was heated to 130C for 10min under microwave irradiation. The cooled mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (2x50mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated. The resulting black solid was absorbed onto silica and purified by column chromatography (4:1 to 1 :1 petrol-EtOAc) to give the product as an orange solid (285mg, 45%).1H NMR (DMSO): 8.43 (1 H, d, J 2.3), 8.19 (1 H, t, J 8.5), 7.96 (1 H, dd, J 4.8 and 2.1), 7.92 (1 H, d, J 2.0), 7.79-7.73 (3 H, m) and 7.15 (1 H, d, J 8.8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | b. 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-amine (VII) A flask was charged with <strong>[833486-94-5]2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (17.3 g, 65.5 mmol) and palladium on carbon catalyst in MeOH (360 mL). Hydrogenation was carried out at 1 atm of hydrogen for 5 hrs. The mixture was filtered through celite, which was washed with MeOH. The solution was used for the next step without further purification. To the above solution, cyanogen bromide (8.4 g, 79.2 mmol) was added at room temperature. The mixture was stirred at room temperature for 1.5 hrs and then concentrated. Sat. NaHCO3 was poured to the residue and the precipitated solid was collected by filtration, washed with EtOAc, and dried under vacuum to give the title compound (12.05 g, 71%). 1H-NMR (400 MHz, d6-DMSO) delta 8.27 (s, 1H), 7.70 (s, 2H), 7.55 (d, 1H), 6.97 (d, 1H) and 1.27 (s, 12H); MS (ESI) (M+H)+ 260. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 16h;Inert atmosphere; | A mixture of 2-nitro-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)- phenylamine (264 mg, 1 .00 mmol, as prepared in Example 17, step A) and 2- bromo-1-fluoro-3-trifluoromethyl-benzene (243 mg, 1.00 mmol) in DME (5 mL) and 2 M aqueous Na2CO3 (4 mL, 8 mmol) was degassed via sonication, placed under argon and treated with Pd (PPh3)4 (1 15 mg, 0.100 mmol). The resulting mixture was heated at 800C for 16 h and allowed to cool to room temperature. The resulting mixture was diluted with EtOAc (10 mL) and washed twice with water (10 mL). The aqueous layer was extracted with additional EtOAc (10 mL), and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified on silica (EtOAc/hexanes, 0:100 to 50:50, v/v) to yield 6'-fluoro-3-nitro-2'-thfluoromethyl-biphenyl-4-yl- amine. 1H-NMR (CDCI3) delta: 8.1 1 (d, J = 2.0 Hz, 1 H), 7.56 - 7.60 (m, 1 H), 7.49 (td, J = 7.9, 5.4 Hz, 1 H), 7.28 - 7.39 (m, 2H), 6.88 (d, J = 8.6 Hz, 1 H), 6.20 (br. s., 2H) | |
With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; at 90℃; for 24h;Inert atmosphere; | To a mixture of 1-bromo-2-fluoro-6-trifluoromethylbenzene (0.850 mL, 6.09 mmol), <strong>[833486-94-5]4-amino-3-nitrophenylboronic acid pinacol ester</strong> (2.09 g, 7.92 mmol), and (dppf)PdCl2.DCM (249 mg, 0.300 mmol) under Ar was added DME (24 mL) and 2 M aqueous Na2CO3 (8.00 mL, 16.0 mmol). The resulting mixture was stirred at 90 C. for 24 h, cooled to room temperature, diluted with EtOAc (25 mL), and washed sequentially with water (10 mL) and brine (10 mL). The resulting solution was dried over MgSO4 and filtered. The solvent was removed under reduced pressure, and the resulting residue was chromatographed using a 80-g SiO2 pre-packed column eluting with 0:1 to 2:3 EtOAc-hexanes to yield a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 8.10 (s, 1H), 7.53-7.61 (m, 1H), 7.43-7.53 (m, 1H), 7.35 (t, J=8.5 Hz, 1H), 7.30 (d, J=7.3 Hz, 1H), 6.89 (d, J=8.3 Hz, 1H), 5.47 (br. s., 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90℃; for 12h; | 7-Bromo-4-[4-(difluoromethyl)piperidin-l-yl]carbonyl}-2,3,4,5- tetrahydro-l,4-benzoxazepine (356 mg, 0.91 mmol) and 2-mtro-4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)aniline (240 mg, 0.91 mmol) were taken into dioxane (10 mL) and water (1 mL) followed by addition of dichloro[ 1,1 -bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (74 mg, 0.09 mmol) and cesium carbonate (1.5 g, 4.55 mmol). The mixture was then heated to 9O0C over 12h then cooled to room temperature and diluted with ethyl acetate. The aqueous phase was extracted once with with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate then filtered and concentrated. The residue was purified by silica gel chromatography using 10% ethyl acetate in hexanes to 100% ethyl acetate as eluent to give 4-(4-[4-(difluoromethyl)piperidin-l-yl]carbonyl}-2,3,4,5- tetrahydro-l,4-benzoxazepin-7-yl)-2-nitroaniline (350 mg, 86%). 1H NMR (400 MHz, CDCl3): 8.30 (d, IH), 7.59 (dd, IH), 7.40-7.38 (m, 2H), 7.08 (d, IH), 6.89 (d, IH), 6.13 (br s, 2H), 5.64 (d tr, CHF2, IH), 4.44 (s, 2H), 4.19 (m, 2H), 3.78 (d, 2H), 3.71 (m, 2H), 2.80 (tr, 2H), 2.02-1.93 (m, IH), 1.80 (d, 2H), 1.50 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With potassium phosphate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; sealed tube; | To a solution of l-[(7-bromo-2,3-dihydro-l,4-benzoxazepin-4(5H)- yl)carbonyl]-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol (0.688 g, 1.38 mmol) and 2-nitro-4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline (0.365 g, 1.38 mmol) in dioxane (24 mL) and water (3.00 ml) was added tribasic potassium phosphate (0.413 g, 1.79 mmol). The solution was sparged with N2(g) for ten minutes before the addition of dichloro[l,l-bis- (diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.023 g, 10 mol %). The resulting suspension was heated at 90 0C for 2 hours in a sealed tube vessel. On cooling to room temperature the mixture was diluted with ethyl acetate (50 mL), washed with water (50 mL) and then dried over anhydrous sodium sulfate. Filtration and concentration afforded a crude orange oil that was purified by silica gel chromatography (7:3 hexanes/ethyl acetate) to provide l-[7-(4-amino-3-nitrophenyl)-2,3-dihydro-l,4-benzoxazepin-4(5H)-yl]carbonyl}- 4-[3-(trifluoromethyl)phenyl]piperidin-4-ol (0.200 g, 26% yield) as an orange oil. MS (EI) for C28H27F3N4O5: 557 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.83% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane;Reflux; | 4- 5-Methoxy-4-mo holin-4-yl-pyrimidin-2-yl')-2-nitro-phenylamine[0087] A mixture of 4-(2-chloro-5-methoxy-pyrimidin-4-yl)-morpholine (1.0 g, 1 eq.), 2-nitro-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenylamine (1.26 g, 1.1 eq.), dioxane (20 ml), Pd(PPh3)4 (0.05 g, 0.1 eq.) and 2M sodium carbonate (6.53ml, 3.0eq.) was heated to reflux overnight. The solvent was removed in vacuo, the residue extracted with EA, and the organic layer washed with brine and dried. The crude was purified by chromatography to give a brown solid (2.08 g, 47.83%). 'H NMR (500 MHZ, CDCl3-di): 69.06(s, 1 H), 8.32-8.34(d, 1 H), 7.98(s, 1 H), 6.84-6.86(d, 1 H), 6.20(s, 2H), 3.86(s, 3H), 3.84(s, 8H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With sodium dithionite; In ethanol; water; at 160℃; for 0.166667h;Microwave irradiation; | Example 1 : Preparation of compounds of general formula f I) ^pyridi ^-y -S^ASjS^etramethyl-I.S^^ioxaborolan^- ^-IH^enzoIdJimidaaoIe (Intermediate A)To a stirred solution of 2-nitro-4-(4>4.5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)aniline {1.58 g, 6.0 mmol) and 4-pyridinecarboxaldehyde (0.622 mL» 6.6 mmol) in ethanol (7.5 mL) and H20 (7.5 mL), was added sodium dithionite (2.09 g, 12.0 mmol). The suspension was heated to 160 C for 10 minutes in the CEM microwave. The resulting dark coloured suspension was absorbed onto silica and purified by flash chromatography eluting with (0:100 EtOAc-Hexane to 100:0 (EtOAc-Hexane) to yield title compound as a yellow solid (0.82 g, 2.5 mmol, 42%).LCMS RT=1.79 min, MH* 322.1; 1H NMR (CDCI3): 8.68-8 58 (2 H, m), 8.13 (1 H, s), 8.07- 8.00 (2 H, m), 7.78-7.66 (2 H, m) and 1.30 (12 H, s). |
42% | With sodium dithionite; In ethanol; water; at 160℃; for 0.166667h;Microwave irradiation; | Example 1: Preparation of compounds of general formula (I)2Kpyridln^-yl)-5^4,4,5l5-te amethyl-1,3,2-dioxaborolan-2-yl)-1 H-benzo[d]imidazole (Intermediate A)To a stirred solution of 2-nitro-4-(4,4,5,5-tetramethyl-1 ,3l2-dioxaborolan-2-yl)aniline (1.58 g, 6.0 mmol) and 4-pyridinecarboxaldehyde (0.622 mL, 6.6 mmol) in ethanol (7.5 mL) and H20 (7.5 mL), was added sodium dithionite (2.09 g, 12.0 mmol). The suspension was heated to 160 C for 10 minutes in the CEM microwave. The resulting dark coloured suspension was absorbed onto silica and purified by flash chromatography eluting with (0:1 EtOAc-Hexane to 1:0 (EtOAc-Hexane) to yield title compound as a yellow solid (0.82 g, 2.5 mmol, 42%).LCMS RT=1.79 min, MhT 322.1 ; H NMR (CDCI3): 8.68-8.58 (2 H, m), 8.13 (1 H, s), 8.07- 8.00 (2 H, m), 7.78-7.66 (2 H, m) and 1.30 (12 H, s). |
Tags: 833486-94-5 synthesis path| 833486-94-5 SDS| 833486-94-5 COA| 833486-94-5 purity| 833486-94-5 application| 833486-94-5 NMR| 833486-94-5 COA| 833486-94-5 structure
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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.
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