Structure of 476620-22-1
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CAS No. : | 476620-22-1 |
Formula : | C9H9BN2O2 |
M.W : | 187.99 |
SMILES Code : | OB(C1=CC=CC(N2N=CC=C2)=C1)O |
MDL No. : | MFCD05864582 |
InChI Key : | NMBKAXJHGMDYGA-UHFFFAOYSA-N |
Pubchem ID : | 16640530 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
53% | With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 150℃; for 0.166667h;Microwave irradiation; | Step c: ((3aR,4R,6R,6aR)-2>2-Dimethyl-6-{6-[3-(lH-pyrazol-l-yl)phenyll-9H-purin-9-yl)- tetrahydrofuror3,4-rfl[131dioxol-4-yl)methyl acetate; [0361] [(3aR,4JR,6R,6aR)-6-(6-Bromo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro-[3,4-d][l,3]dioxol-4-yl]methyl acetate (0.1 g, 0.242 mmol), 3-(l-H-pyrazole-l- yl)phenylboronic acid (0.137 g, 0.726 mmol), potassium phosphate (0.154 g, 0.726 mmol), and [l,l"-bis(diphenylphosphino)ferrocene]dichloropalladium(?), complex dichloromethane (1:1) (0.040 g, 0.048 mmol) were placed in an oven-dried microwave vial and degassed with argon. Anhydrous dioxane (1.5 mL) was added and the reaction was heated to 150 0C for ten minutes in the microwave. The mixture was filtered through a pad of Celite washing with dichloromethane then concentrated. The residue was taken up in dichloromethane and purified on a prep plate using 60 % ethyl acetate/hexanes as developing solvent to give the title compound as a yellow solid (0.061 g 53 %).[0362] LCMS: R.t. 1.84 min ES+ 477 (formic acid) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 4.0h;Heating / reflux; | A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)-benzyl]-4-methyl- l,3-oxazolidin-2-one (0.05 g, 0.084 mmol), 3-(lH-pyrazol-l-yl)phenyl boronic acid (0.031 g, 0.167 mmol), tetrakis(triphenylphosphine) palladium ( 5% mol) and sodium carbonate (0.019 g, 0.18 mmol) in 7 ml of water/EtOH/toluene (1:2:4) was heated to reflux for 4 h. TLC (EtOAcrhexane /1 : 1) showed that the reaction was over. The solvents were removed. Water (10 ml) was added. The organic was extracted with methylene chloride (3x 10 ml). The combined methylene chloride layers were washed with brine, and dried over sodium sulfate. The title compound was obtained after flash column using EtOAc:hexane /1:1 as the eluant. 1H NMR (CDCl3, 500 MHz): delta 8.02 (d,J=2.5 Hz, IH), 7.88 (s, IH), 7.84 (s, IH), 7.77 <n="105"/>(S7 IH), 7.76 (s, IH), 7.75 (s, 2H), 7.73 (m, IH), 7.71 (m, IH), 7.61 (t, J= 7.5 Hz, IH), 7.53 (d, J= 7.5 Hz, IH), 7.26 (m, IH), 6.54 (t, J = 2 Hz, IH), 5.55 (d, J= 7.5 Hz, IH), 5.02 (d, J= 16 Hz, IH), 4.21 (d, J = 16 Hz, IH), 3.82 (m, IH), 0.54 (d, J= 6.5 Hz, 3H). LC-MS (M+l): 614.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | With potassium carbonate; dimethyl sulfoxide; In 1,4-dioxane; water; | Example 164 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[3-(1H-pyrazol-1-yl)phenyl]-1H-indole-7-carboxamide To 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (20 mg, 0.048 mmol) was added <strong>[476620-22-1][3-(1H-pyrazol-1-yl)phenyl]boronic acid</strong> (36 mg, 0.193 mmol), dioxane (2.8 mL) and a solution of potassium carbonate (20 mg) in water (1.2 mL). To this mixture was added chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (3 mg, 0.005 mmol). The resulting mixture was reacted in a CEM microwave for 10 min at 160 C. then concentrated under a stream of nitrogen (greenhouse) at 80 C. The crude product was partitioned between water (2 mL) and CH2CL2 (2 mL). The layers were separated with a hydrophobic frit, and the aqueous layer was extracted with CH2CL2 (2*2 mL). The organic layers were pooled and concentrated under a stream of nitrogen at 80 C. Dimethyl sulfoxide (0.8 mL) was added to residue, which was sonicated for 10 sec. filtered through a cotton plug, and then filtered through a 0.2 mum filter. The crude product was purified on an Agilent MDAP using a Zorbax Eclipse XDB 610 21.2*50 mm column to afford 2.3 mg of the title compound (10%). LC/MS=m/z 478.2 [M+H] Ret. Time: 2.05 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.166667h;Microwave radiation; | 3-(3-Bromo-imidazo[1,2-a]pyridine-7-yl)-N-methyl-benzamide (Intermediate EA) (1 eq, 0.303 mmol, 100 mg) and <strong>[476620-22-1]3-(1H-pyrazolyl)-phenylboronic acid</strong> (1.3 eq, 0.394 mmol, 74 mg) are dissolved in DME (3 ml) and water (0.8 ml) and Na2COs (3 eq, 0.909 mmol, 96.3 mg) is added. PdCl2(PPh3)I (0.05 eq, 0.015 mmol, 10.6 mg) is added and the reaction mixture is heated using microwave radiation at 120C for 10 min. At the completion of this time the solvent is removed in vacuo and the reaction mixture is purified by flash column chromatography eluting with 9:1 DCM/MeOH to yield N- methyl-3-[3-(3-pyrazol-1-yl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-benzamide as a light brown solid; [M+H]+ = 395 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.166667h;Microwave radiation; | 3-Bromo-7-chloro-imidazo-[1,2-a]-pyridine (1 eq, 2.59 mmol, 600 mg) and 3-(1H- pyrazolyl)-phenylboronic acid (1.2 eq, 1.04 mmol, 195 mg) are dissolved in DME (5 ml) and water (1.5 ml) and Na2CO3 (0.65 eq, 1.68 mmol, 209 mg) is added. PdCl2(PPh3)2 (0.04 eq, 0.104 mmol, 72.8 mg) is added and the reaction mixture is heated using microwave radiation at 120C for 10 min. At the completion of this time <n="116"/>the solvent is removed in vacuo and the reaction mixture is purified by flash column chromatography eluting with 9:1 DCM/MeOH to yield 7-chloro-3-(3-pyrazol-1-yl- phenyl)-imidazo[1,2-a]pyridine as a brown solid; [M+H]+ = 295 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 1.0h;Sealed tube; Microwave irradiation; | EXAMPLE 1276-[3-(lH-Pyrazol-l-yl)phenyl]quinoxaline6-Bromoquinoxaline (100 mg, 0.48 mmol), 3-(lH-pyrazol-l-yl)phenylboronic acid (108 mg, 0.57 mmol), Na2CO3 (0.15 g, 1.44 mmol), Pd(PPh3)4 (55 mg, 0.048 mmol), water (2 mL) and DME (6 mL) were combined in a sealed tube and heated under microwave irradiation to 12O0C for 1 h. The reaction mixture was concentrated to dryness and purified by preparative EtaPLC to give the title compound (62.1 mg, 47%) as a pale yellow solid. deltaEta (CDCl3) 8.89 (IH, d, J 1.84 Hz), 8.86 (IH, d, J 1.84 Hz), 8.38 (IH, d, J2.05 Hz), 8.20 (IH, d, J8.74 Hz), 8.15-8.09 (2H, m), 8.03 (IH, d, J2.51 Hz), 7.78 (IH, d, J 1.76 Hz), 7.75 (IH, ddd, J8.00, 2.25, 1.14 Hz), 7.69-7.66 (IH, m), 7.63-7.55 (IH, m), 6.52 (IH, dd, J2.50, 1.78 Hz). LCMS (ES+) 273 (M+H)+, 15.14 minutes {Method 4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;bis(triphenylphosphine)palladium(II)-chloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.166667h;Microwave irradiation; | 4-(3-Bromo-imidazo[1,2-b]pyridazin-7-yl)-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one (1.0 eq, 0.096 mmol, 40 mg), <strong>[476620-22-1][3-(1H-pyrazol-1-yl)phenyl]boronic acid</strong> (1.50 eq, 0.144 mmol, 28.5 mg) and Na2CO3 (2.0 eq, 0.192 mmol, 20.4 mg) are dissolved in DME/H2O (3/1 ml) and PdCl2(PPh3)2 (0.1 eq, 0.0096 mmol, 6.74 mg) is added. The reaction mixture is then heated in a microwave at 120 C. for 10 min. At the completion of this time the solvent is removed in vacuo and the product is purified by flash column chromatography eluting with CH2Cl2/MeOH (80:20) to give 1-(3-piperidin-1-yl-propyl)-4-[3-(3-pyrazol-1-yl-phenyl)imidazo[1,2-b]pyridazin-7-yl]-1H-pyridin-2-one as a yellow solid; [M+H]+=480 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
249 mg | With tetrakis(triphenylphosphine) palladium(0); copper(I) thiophene-2-carboxylate; In tetrahydrofuran; at 85℃; for 1.25h;Inert atmosphere; Microwave irradiation; | A solution of the product obtained in the previous step (250 mg, 0.89 mmol), copper(l)- thiophene-2-carboxylate (252 mg, 1.3 mmol) and 3-(1 H-pyrazol-1 -yl)phenylboronic acid (318 mg, 1.3 mmol) in THF (5 ml) was purged with nitrogen gas for 10 minutes.Tetrakis(triphenylphosphine)palladium(0) (51 mg, 0.044 mmol) was added and the mixture was heated to 85 C for 75 minutes by microwave irradiation. Ethyl acetate was added and the mixture was filtered through celite. The organic phase was washed with a saturated aqueous sodium bicarbonate solution and then dried by passing through a hydrophobic frit. The solution was concentrated under reduced pressure to give a crude residue that was purified by normal phase chromatography, eluting with CH2CI2 containing an increasing amount of ethyl acetate to give ethyl 1 -(2-(3-(1 H-pyrazol-1 -yl)phenyl)pyrimidin-4-yl)piperidine-4-carboxylate, as an off white solid (249 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.05 g | With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium carbonate; In 1,4-dioxane; water; at 85℃; for 2.0h;Inert atmosphere; | The product obtained in the previous step (5.92 g, 18.1 mmol), <strong>[476620-22-1]3-pyrazolephenylboronic acid</strong> (3.41 g, 18.1 mmol), potassium carbonate (7.51 g, 54.3 mmol) and Pd(dppf)2CI2 were dissolved in dioxane:water (150 ml, 9:1 ). After purging with N2 for 15 minutes, the reaction mixture was heated to 85 C for 2 hours and then cooled to ambient temperature. The solvents were removed under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was separated and concentrated under reduced pressure giving a dark solid (9.59 g). The crude solid was purified using normal phase chromatography eluting with /'so-hexane and increasing amounts of ethyl acetate to give tert-butyl (1 -(2-(3-(1 H-pyrazol- 1 -yl)phenyl)pyrimidin-4-yl)piperidin-4-yl)methylcarbamate as a pink solid (6.05 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.333333h;Microwave irradiation; | General procedure: Method Q Parallel preparation of Examples 60-71. To a set of microwave vials containing mixtures of reactant PI (25 mg, 0.067 mmol), the appropriate boronic acid or pinocol ester (1.5 equiv.), and [1,1'- bis(diphenylphosphino)ferrocene]dichloro palladium(II)(9.82 mg, 0.013 mmol) in 1,4-dioxane (2 mL) was added potassium carbonate (27.8 mg, 0.20 mmol) in water (0.20 mL). Reactions were carried out at 120 C for 20 minutes in a microwave reactor. Water (2mL) and EtOAc (2 mL) were added, stirred for 10 minutes. The organic layers were separated, transferred to a set of vials, and concentrated. Each crude product was redissolved in 1 mL of DMSO and filtered. The crude products were purified by mass triggered HPLC (Waters XBridge CI 8 column, 5muiotaeta, 19x100 mm, using gradient ranges from 10-30% initial to 35-98% final MeCN (0.1% NH4OH) in water (0.1% NH4OH) to provide the Examples 60-71. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; potassium hydroxide; In 1,4-dioxane; water; at 95℃; for 3.0h; | A mixture of {R,E)- fe/f-butyl 4-(3-(2-(l,8-naphthyridin-2-yl)ethyl)pyrrolidin-l-yl)but-2-enoate (Intermediate 12) (333 mg, 0.906 mmol), (3-(l pyrazol-l-yl)phenyl)boronic acid (available from ABCR GmbH) (511 mg, 2.72 mmol), aq. KOH (3.8M, 0.477 mL, 1.81 mmol), chloro(l,5- cyclooctadiene)rhodium(I) dimer (44.7 mg, 0.091 mmol), (tf)-BINAP (113 mg, 0.196 mmol) in 1,4- dioxane (15 mL) was heated for 3 h at 95 C. The reaction mixture was concentrated in vacuo and partitioned between DCM (25 mL) and water (25 mL). The aqueous layer was separated and extracted with further DCM (25 mL), and the combined organic solutions were concentrated in vacuo. The residue was dissolved in DCM and purified by chromatography on a silica cartridge (50 g), eluting with 0 - 25% MeOH - DCM. The appropriate fractions were combined and evaporated in vacuo to give the title compound (128 mg, 28%) as an orange oil : LCMS (System A): RT = 1.22 min, ES+ve m/z 512 (M+H)+; Analytical Chiral HPLC Chiralpak AD (250 mm x 4.6 mm), eluting isocratically with 30% EtOH - heptane containing 0.1% isopropylamine, flow rate 1 mL/min, detecting at 235 nm : RT = 7.05 min, 95% (major isomer) and 12.2 min, 5% (minor isomer). |