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Product Details of 1-Boc-pyrazole-4-boronic acid pinacol ester

CAS No. :552846-17-0
Formula : C14H23BN2O4
M.W : 294.15
SMILES Code : C1=C(C=N[N]1C(OC(C)(C)C)=O)B2OC(C(O2)(C)C)(C)C
MDL No. :MFCD05663873
InChI Key :IPISOFJLWYBCAV-UHFFFAOYSA-N
Pubchem ID :16217654

Safety of 1-Boc-pyrazole-4-boronic acid pinacol ester

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 1-Boc-pyrazole-4-boronic acid pinacol ester

* 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.

  • Downstream synthetic route of [ 552846-17-0 ]

[ 552846-17-0 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 552846-17-0 ]
  • [ 1206800-24-9 ]
  • [ 1206800-43-2 ]
  • [ 1206800-42-1 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 1,1'-bis(di-tertbutylphosphino)ferrocene; In 1,4-dioxane; water; at 60℃;Inert atmosphere; Preparation 101 tert-Butyl 4-(5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylateTo a 12 L round bottom flask equipped with overhead agitation, a thermocouple, heating mantle, condenser, and subsurface nitrogen sparge is added 1,4-dioxane (7.44 L) and water (1.67 L). The solution is purged with N2 (inlet tube). Next <strong>[1206800-24-9]6-bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole</strong> (595 g, 1.63 mol) is added and the solution is purged with N2 again. tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (717.02 g, 2.44 mol), potassium phosphate tribasic N-hydrate (689.8 g, 3.25 mol), and 1,1'-Bis(di-tert-butylphosphino)ferrocene (7.71 g, 16.25 mmol) are added. Finally, Pd2(dba)3 (7.44 g, 8.13 mmol) is added. The solution is purged for 15 min and then heated at 60 C. for 12 hours. The reaction is not complete and more Pd2(dba)3 (7.44 g, 8.13 mmol) is added. The solution is again heated at 60 C. for 3 additional hours and the reaction is complete. 1,4-Dioxane is then removed (Buchi bath temp 60 C.) and the residue is re-dissolved in 10 volumes (6 L) of DCM. Water (3 L) is added and then the layers are separated. The organic solution is dried over Na2SO4, filtered and concentrated to a dark oil (835 g). The material is not purified and is forward processed to the next step. The material is about 60% desired product and about 40% 5-(2-fluoro-4-nitrophenoxy)-1-methyl-6-(1H-pyrazol-4-yl)-1H-indazole. The crude obtained is reprotected in the next step. It is assumed that 50% of the crude product is the 5-(2-fluoro-4-nitrophenoxy)-1-methyl-6-(1H-pyrazol-4-yl)-1H-indazole.To a 22 L round bottom flask with overhead agitation, thermocouple, 1 L addition funnel, N2 purge, and cooling bath is added a solution of crude 5-(2-fluoro-4-nitro-phenoxy)-1-methyl-6-(1H-pyrazol-4-yl)- 1H-indazole (835 g, 1. 18 mol) in DCM (6 L) of. phenoxy)-1-methyl-6-(1H-pyrazol-4-yl)-1H-indazole (835 g, 1.18 mol) in DCM (6 L) of di-tert-butyldicarbonate (283.69 g, 1.30 mol) dissolved in DCM (350 mL) of is added to an addition funnel. The solution is added dropwise over 48 min. After the reaction is complete, DCM is removed by rotary evaporation to give a dark oil. To the dark oil is added MTBE (2.5 L) and the oily solution is cooled to about 0-5 C. The solution is seeded with material obtained in Preparation 98. After seeding, crystallization is observed and the resulting slurry is stirred for 30-40 min. The pale yellow slurry is filtered over a polypropylene pad and the cake is washed with cold (0-5 C.) MTBE (1.5 L). The solids are dried in a 40 C. vacuum oven overnight to give the desired product (443 g, 60% crude yield). MS (m/z): 354.0 (M+H). The material is shown to be about 93-95% pure by HPLC and is therefore forward processed.
  • 2
  • [ 552846-17-0 ]
  • [ 1001070-33-2 ]
  • [ 1147998-27-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 1.08h; EXAMPLE 2; Compound 2-1; 3-r6-(piperidin-4-yloxy)rhoyrazin-2-yll-5-(lH-pyrazol-4-yl)-lH-pyrrolor2,3-blPvridine; )h 1 -(phenylsulfonylV5-(lH-pwazol-4-vD-lH-pyrrolor2, 3-fr|pyridine; To a degassed (sparging with argon for 5 minutes), stirred solution of 4-(4 ,4,5,5- tetramethyl-l,3,2-dioxaborolan-2yl)-pyrazole-l-carboxylic acid tert-butyl ester (1.31 g, 4.45 mmol) and 5-bromo-l-(phenylsulfonyl)-lH-pyrrolo[2,3->]pyridine (1.00 g, 2.97 mmol) in dioxane (12.0 ml) was added Pd(Ph3P)4 (0.171 g, 0.148 mmol), followed by a degassed aqueous <n="51"/>solution of sodium carbonate (4.45 ml, 8.90 mmol). The reaction mixture was stirred under nitrogen at 100 0C for 1 hour. The reaction mixture was cooled to room temperature and partitioned between EtOAc (50 mL) and saturated aqueous ammonium chloride (50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude residue. The residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford 1 - (phenylsulfonyl)-5-(l/-/-pyrazol-4-yl)-lH-pyrrolo[2, 3-£]pyridine as a yellow solid. LRMS (ESI) calculated for C16HnN4O2S [M+H]+, 325.1; found 325.0.
  • 3
  • [ 552846-17-0 ]
  • [ 62224-16-2 ]
  • [ 1239576-68-1 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; at 85℃; for 6h;Sealed flask; Example 2; Preparation of Lambda/-{(1 S)-2-amino-1-[(3,4-difluorophenyl)methyl1ethyl}-5-chloro-4-(1 /-/- pyrazol-4-yl)-2-thiophenecarboxamide; a) 1 ,1-dimethylethyl 4-{5-[(methyloxy)carbonyl]-3-thienyl}-1 H-pyrazole-1-carboxylate; To a 75 ml. sealed flask was added <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong> (1.144 g, 5.17 mmol) [prepared according to the procedure of Example 1], potassium carbonate (2.31 g, 16.71 mmol), 1 ,1-dimethylethyl 4-(4,4, 5, 5-tetramethyl-1 , 3,2- dioxaborolan-2-yl)-1 H-pyrazole-1-carboxylate (1.656 g, 5.63 mmol) and bis(tri-t- butylphosphine)palladium(O) (35.1 mg, 0.069 mmol) in 1 ,4-dioxane (20 ml.) and H2O (4 ml_). After stirring for 6 hours at 85 0C, the reaction solution was diluted with CHCI3 (75 ml.) and washed with H2O. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was adsorbed onto silica gel and eluted with [Hexanes/EtOAc, 2:1 ] to give the product [774 mg, quant.] as a yellow oil: LCMS (ES) m/z 309 (M+H)+.
  • 4
  • [ 552846-17-0 ]
  • [ 1187932-25-7 ]
  • [ 1466528-30-2 ]
YieldReaction ConditionsOperation in experiment
74.5% To a degassed solution of Intermediate 1 1A (3.00 g, 9.99 mmol), tert-butyl 4- (4,4,5, 5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole-l-carboxylate (4.410 g, 14.99 mmol) and potassium carbonate (4.14 g, 30.0 mmol) in dioxane (20 mL)/water (8 mL) was added Tetrakis (0.577 g, 0.500 mmol). The vial was purged with argon, sealed and stirred at 90 C for 16 h. Another 20% of tetrakis and boronic ester were added and the reaction mixture was degassed and heated at 90 C for 24 h. The reaction was cooled down to rt and NaOH (14.99 mL, 14.99 mmol) was added and the reaction was stirred at 50 C for 5 h. The mixture was partitioned between EtOAc and water. The organic layer was separated. The aqueous phase was extracted with EtOAc, and the combined organic layers were dried over MgS04 and concentrated in vacuo. The crude material was purified by flash chromatography over 120 g of silica gel (15 min gradient, with 0-100% ethyl acetate in hexanes) to afford Intermediate 1 IB (2.14 g, 7.45 mmol, 74.5% yield) as a white solid. LCMS = 1.86 min [M+l] = 288.2 (Method B).
  • 5
  • [ 630125-49-4 ]
  • [ 552846-17-0 ]
  • [ 1529769-65-0 ]
YieldReaction ConditionsOperation in experiment
80.9% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium acetate; In 1,4-dioxane; water; at 100℃; for 6h;Inert atmosphere; Add l-bromo-3-nitro-5-(trifluoromethyl)benzene (0.165 g, 0.61 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole-l-carboxylate (0.18 g, 0.61 mmol), sodium acetate (0.1 g, 1.2 mmol), [l,r-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (22 mg, 0.03 mmol) to 1 ,4-dioxane (15 mL) and water (2 mL). Stir the mixture at 100C under N2 for 6 hrs. TLC (EtOAc:PE=l : l) shows that the reaction is complete. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=l :1) affords the title compound (0.17 g, 80.9%). MS: (M+l): 358.2.
80.9% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium acetate; In 1,4-dioxane; water; at 100℃; for 6h;Inert atmosphere; Add <strong>[630125-49-4]1-bromo-3-nitro-5-(trifluoromethyl)benzene</strong> (0.165 g, 0.61 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate (0.18 g, 0.61 mmol), sodium acetate (0.1 g, 1.2 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (22 mg, 0.03 mmol) to 1,4-dioxane (15 mL) and water (2 mL). Stir the mixture at 100 C. under N2 for 6 hrs. TLC (EtOAc:PE=1:1) shows that the reaction is complete. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=1:1) affords the title compound (0.17 g, 80.9%). MS: (M+1): 358.2.
  • 6
  • [ 552846-17-0 ]
  • [ 1206800-24-9 ]
  • [ 1206800-42-1 ]
  • 7
  • [ 552846-17-0 ]
  • [ 1309774-03-5 ]
  • 2-chloro-7-(1H-pyrazol-4-yl)-1,5-naphthyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,4-dioxane; water; at 110℃; for 5h;Inert atmosphere; Example 0646 0646-1 A mixture of <strong>[1309774-03-5]7-bromo-2-chloro-1,5-naphthyridine</strong> (5.0 g), 1-tert-butoxycarbonyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (6.04 g), sodium carbonate (4.4 g), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (366 mg), 1,4-dioxane (24 mL), and water (2.4 mL) was stirred at 110 C. for 5 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, water was added thereto, and the solid matter was collected by filtration. The obtained solid matter was suspended by the addition of ethyl acetate, and the solid matter was collected by filtration, thereby obtaining 2-chloro-7-(1H-pyrazol-4-yl)-1,5-naphthyridine (2.6 g) as a pale brown solid. MS m/z (M+H): 231.
  • 8
  • [ 552846-17-0 ]
  • [ 808744-34-5 ]
  • 7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; N,N-dimethyl-formamide; for 10h;Inert atmosphere; Compound 8 (12.20 g, 61.93 mmol), Compound 26 (20.00 g, 68.03 mmol) was dissolved in DMF (220 mL)Stir well with H2O (100 mL), then add K2CO3 (31.80 g, 230.43 mmol), respectively.Pd(dppf)Cl2·DCM (7.60 g, 9.30 mmol), nitrogen was replaced with air three times and stirred under the protection for 10 hours.The reaction solution was concentrated and purified by silica gel column chromatography. The mobile phase was taken from dichloromethane and methanol (DCM:MeOH = 40:1 to 25:1).A brown solid 27 (8.80 g, 70%) was obtained.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 19h; 1.95 g of B, 3.0 g of C, 6.52 g of Cs2C03 (cesium carbonate) and 40 mg of Pd (dppf) Cl2 ([1,1'-bis(diphenylphosphine) ferrocene] was dissolved in 50 mL of a mixture of 1,4-dioxane and water (1,4-dioxane: water = 4: 1).After replacing the nitrogen three times, the mixture was heated to 90 C, Keep the temperature for 19 hours. After completion of the reaction, the solid residue was filtered off with celite and concentrated, and the resulting viscous solid was used directly in the next step.
  • 9
  • [ 552846-17-0 ]
  • [ 57381-43-8 ]
  • C24H28N4O6 [ No CAS ]
  • 10
  • [ 552846-17-0 ]
  • [ 121554-10-7 ]
  • C23H25N5O4 [ No CAS ]
  • 11
  • [ 552846-17-0 ]
  • [ 808744-34-5 ]
  • tert-butyl 4-imidazo[1,2-a]pyridin-7-ylpyrazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at 70℃; for 3h;Inert atmosphere; A degassed solution of fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole-l- carboxylate (CAS 552846-17-0; 1.50 g, 4.99 mmol, 1.10 eq,), potassium phosphate, K3PO4 (2.91 g, 3.0 eq.), 7-bromoimidazo[l,2-a]pyridine (CAS 808744-34-5; 920 mg, 1.0 eq.) and Pd(dppf)Cl2-DCM complex (190 mg, 0.23 mmol, 0.05 eq.) in dry THF (18 mL) is placed under argon atmosphere and stirred at 70 C for 3 h. The mixture is cooled to RT and diluted with 100 mL of EtOAc. The organic layer is then washed with 200 mL of water followed by 100 mL of brine. After drying over Na2S04 and filtration, the solvent is evaporated. The residue is purified by flash chromatography on silica gel (eluting 0 to 50% (10% MeOH in EtOAc) in EtOAc) to afford fert-butyl 4-imidazo[l,2-a]pyridin-7-ylpyrazole-l- carboxylate.LCMS: MW (calcd): 284.3; m/z MW (obsd): 285.6
 

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