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[ CAS No. 259808-63-4 ]

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Chemical Structure| 259808-63-4
Chemical Structure| 259808-63-4
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CAS No. :259808-63-4 MDL No. :MFCD09746327
Formula : C15H21BrN2O4S Boiling Point : -
Linear Structure Formula :- InChI Key :N/A
M.W :405.31 g/mol Pubchem ID :-
Synonyms :

Safety of [ 259808-63-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 259808-63-4 ]

  • Downstream synthetic route of [ 259808-63-4 ]

[ 259808-63-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 98-58-8 ]
  • [ 57260-71-6 ]
  • [ 259808-63-4 ]
YieldReaction ConditionsOperation in experiment
100% In tetrahydrofuran at 20℃;
100% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 19.5h; Inert atmosphere;
97% With N-ethyl-N,N-diisopropylamine In dichloromethane at 40℃; for 16h; General Method A General procedure: 6 (45mg, 0.10mmol), 4-tert-butylbenzenesulfonyl chloride (24mg, 0.10mmol) and DIPEA (107μL, 0.62mmol) were dissolved in DCM (2mL) and stirred at 40°C for 16h. The reaction was then concentrated in vacuo and the crude material was then purified by column chromatography eluting with 100% DCM to 5% MeOH/DCM to afford 1 as a solid (16.7mg, 40%).
96% With triethylamine In dichloromethane at 20℃; for 2h; 1.2 Preparation of tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate (4): To a solution of 4-bromobenzenesulfonyl chloride (3) (5.1 g, 20 mmol) in dry dichloromethane, N-Boc-piperazine (5.0 g, 27 mmol) and Et3N (5.5 ml, 40 mmol) were added. The mixture was stirred at room temperature for 2 h and monitored by thin layer chromatography. After the reaction is complete. It was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 4 (7.7 g, 96%) as a white solid.
96% With triethylamine In dichloromethane at 20℃; for 2h; Tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate (5). To the solution of compound 4-bromobenzenesulfonyl chloride (5.1 g, 20 mmol) in dry DCM wasadded N-Boc-piperazine (5.0 g, 27 mmol) and Et3N (5.5 mL,40 mmol). The mixturewas stirred at room temperature for 2 h andmonitored by TLC. After the reaction was complete. The mixturewas evaporated under reduced pressure and purified by silica gelcolumn chromatography to obtain compound 5 (7.7 g, 96%) as awhite solid. 1H NMR (500 MHz, CDCl3) d 7.69 (d, J 8.4 Hz, 2H), 7.61(d, J 8.5 Hz, 2H), 3.54e3.47 (m, 4H), 3.03e2.93 (m, 4H), 1.41 (s,9H).
93% With triethylamine In dichloromethane at 20℃; for 2h;
92% With triethylamine In dichloromethane at 0 - 20℃; for 3h; 105 Synthesis of 4-(4-bromo-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester Example 105 Synthesis of 4-(4-bromo-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester To a stirring, 0° C. solution of piperazine-1-carboxylic acid tert-butyl ester (1.17 g, 6.29 mmol, 1.05 equiv) and TEA (1.67 mL, 11.98 mmol, 2.0 equiv) in DCM (10 mL) was added 4-bromo-benzenesulfonyl chloride (1.53 g, 5.99 mmol, 1 equiv). The reaction was allowed to warm to ambient temperature and stir for 3 h. The reaction solvents were evaporated and the resulting solids were dried, washed with water and filtered, yielding a white powder (2.24 g, 92% yield). MS (ESI+): m/z=306.9, LC retention time: 3.17 min. Rf=0.56 (30% EtOAc/hexanes).
92% Stage #1: 1-t-Butoxycarbonylpiperazine With triethylamine In tetrahydrofuran at 0 - 20℃; Stage #2: 4-bromobenzenesulfonyl chloride In tetrahydrofuran for 2h; 3-1 Triethylamine (0.94 ml_, 6.71 mmol) was added to a stirred reaction mixture of N-tert- butoxycarbonyl piperazine (0.50 g, 2.68 mmol) in tetrahydrofuran (6 ml_) at 0 °C, then the reaction mixture was stirred at room temperature for 15 minutes. A solution of 4-bromo-benzenesulfonyl chloride (0.686 g, 2.68 mmol) in tetrahydrofuran (4 ml_) was added to the reaction mixture and stirring continued for another 2 hours. Tetrahydrofuran was evaporated off under reduced pressure, then the reaction mixture was diluted with ethyl acetate (20 ml_). The inorganic materials were filtered off through a celite bed. The filtrate was washed with 2 N aqueous HCI (5 ml_), dried over anhydrous sodium sulfate and concentrated in vacuo to yield 1.00 g (92%) of 4- (4-bromo-benzenesulfonyl)-piperazine-1 -carboxylic acid terf-butyl ester as a white solid, which was used in the next step without further purification. MS cald. for Ci5H2IBrN2O4S [(M+NH4)+] 422, obsd. 422.1.
91% With triethylamine In 1,4-dioxane at 20℃; for 1h; To a solution of tert-butyl 1-piperazine-carboxylate (932 mg, 5 mmol) and triethyl amine (836(J,L, 6 mmol) in dioxane (10 mL) was added 4-bromo-benzenesulfonyl chloride (1.28 g, 5 mmol).A white precipitate begins to form almost immediately. The reaction mixture was stirred for 1hour at room temperature and the filtered. The filtrate was concentrated in vacua to yield theproduct as a shiny white solid (1.85 g, 91%). *H NMR (CDC13) 5 1.44 (s, 9H), 3.01 (t, 4H, J =5.1 Hz), 3.53 (t, 4H, J= 5.1 Hz), 7.64 (dt, 2H, /= 2.1, 8.7 Hz), 7.70 (dt, 2H, J = 2.1, 8.7).
83% Stage #1: 1-t-Butoxycarbonylpiperazine With triethylamine In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 4-bromobenzenesulfonyl chloride In tetrahydrofuran at 20℃; for 0.833333h; 1 Step 1-Tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate To a solution of tert-butyl piperazine-1-carboxylate (20.1 g, 108 mmol) in THF (250 mL) was added TEA (19.8 g, 196 mmol) at 0° C. The mixture was stirred at 0° C. for 10 minutes, then 4-bromobenzene sulfonylchloride (25.0 g, 97.8 mmol) was added to the reaction mixture. The reaction mixture was then allowed to warm to rt and stirred for 50 minutes. On completion, the reaction mixture was filtered and concentrated in vacuo. The residue was washed with water (100 mL) and 10% HCl (50 mL), and then extracted with DCM (2×50 mL). The organic layer was washed with NaHCO3 (50 mL) until the pH=8. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a residue. The residue was purified by column chromatography (petroleum ether/ethyl acetate=0:1) to give the title compound (33 g, 83% yield)) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.72-7.70 (m, 2H), 7.64-7.62 (m, 2H), 3.54 (t, J=4.8 Hz, 4H), 3.00 (t, J=4.8 Hz, 4H), 1.43 (s, 9H).
83% Stage #1: 1-t-Butoxycarbonylpiperazine With triethylamine In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 4-bromobenzenesulfonyl chloride In tetrahydrofuran at 25℃; for 0.833333h; 22.1 Step 1: tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate (3): To a solution of tert-butyl piperazine-1-carboxylate (20.1 g, 108 mmol) in THF (250 mL) was added TEA (19.8 g, 196 mmol). The mixture was stirred at 0 °C for 10 minutes. Then 4- bromobenzene sulfonylchloride (25.0 g, 97.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 25 °C for 50 minutes. On completion, the reaction mixture was filtered and concentrated in vacuo. The residue was washed with water (100 mL) and 10 % HCl (50 mL), and then extracted with DCM (2 X 50 mL). The organic layer was washed with NaHCO3 (50 mL) to pH = 8. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a residue. The residue was purified by column chromatography (petroleum ether/ethyl acetate = 0:1) to give the title compound (33 g, 83% yield)) as a white solid. 1H NMR (400MHz, CDCl3) d 7.72 - 7.70 (m, 2H), 7.64 - 7.62 (m, 2H), 3.54 (t, J = 4.8 Hz, 4H), 3.00 (t, J = 4.8 Hz, 4H), 1.43 (s, 9H)
74% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 15h; 33.33(a) Example 33{a) l-(tert-Butoxycarbonyl)-4-(4-bromo-benzenesulfonyl)-piperazine20 JV-boc-Piperazine (0.5 g, 2.68 mmol) and diisopropyethylamine (0.69 g, 5.36 mmol) were dissolved in CH2Cl2 (50 mL) and cooled to O0C. 4-Bromo-phenylsulphonyl chloride (0.68 g, 2.68 mmol) in CH2Cl2 (10 mL) was added dropwise under vigorous stirring. After stirring for 15h at r.t. the reaction mixture was washed with saturated aqueous NaHCO3 EPO (2x20 mL), brine, then dried (Na2SO4) and concentrated to dryness. The solid residue was recrystallized from heptane/EtOAc mixture (2:1), filtered and washed with cold heptane. The title compound was obtained (0.8 g, 74%) as a white solid. 1H NMR (CDCl3, 300 MHz) δ 7.68 (d, J= 8.4 Hz, 2 H), 7.61 (d, J= 8.4 Hz, 2 H), 3.54-3.47 (m, 4 H), 3.01-2.94 (m, 4 H), 1.41 (s, 9 H).
53% With pyridine; dmap at 60℃; for 18h; 6.a a) 4-Bromo-1 -[((4-terf-butoxycarbonyl)piperazin-1 -yl)sulfonyl]benzeneTo a solution of 4-bromobenzenesulfonyl chloride (10 g, 39.13 mmol) in pyridine (120 ml_), DMAP (1 mg) and 1 -te/t-butoxycarbonylpiperazine (7.20 g, 39.13 mmol) were added. The mixture was stirred at 60 0C for 18 h. It was cooled until room temperature and evaporated. The residue was washed with a saturated aqueous solution of NaHCO3 and extrated thrice with EtOAc. The organic phase was dried over Na2SO4 and concentrated to dryness. The crude product obtained was chromatographed over silica gel using Hexane/EtOAc mixtures of increasing polarity as eluent, to afford 8.50 g of the desired compound (53% yield).
With N-ethyl-N,N-diisopropylamine In dichloromethane [Referential Example 276] 1-(4-Bromophenylsulfonyl)-4-(tert-butoxycarbonyl)piperazine [Referential Example 276] 1-(4-Bromophenylsulfonyl)-4-(tert-butoxycarbonyl)piperazine Diisopropylethylamine (4.00 ml) was added to a solution of 4-bromobenzenesulfonyl chloride (3.00 g) and 1-(tert-butoxycarbonyl)piperazine (2.40 g) in methylene chloride (50 ml) at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was concentrated under reduced pressure. The residue thus obtained was purified by chromatography on a silica gel column (hexane: ethyl acetate = 4:1 → 1:1), followed by reprecipitation in a hexane - methylene chloride system, whereby the title compound (4.47 g) was obtained as a colorless solid. 1H-NMR (CDCl3) δ: 1.41(9H,s), 2.97(4H,t,J=5.1Hz), 3.51(4H,t,J=5.1Hz), 7.61(2H,d,J=8.8Hz), 7.69(2H,d,J=8.8Hz). MS (FAB) m/z: 405 [(M+H)+, Br79], 407 [(M+H)+, Br81], 349 [(M+H-isobutene)+, Br79], 351 [(M+H-isobutene)+, Br81], 305 [(M+H-isobutene-CO2)+, Br79], 307 [(M+H-isobutene-CO2)+, Br81].
With triethylamine In dichloromethane at 20℃; for 2.5h; 108 Example 108. 4-(4-Bromo-benzenesuIfonyl)-piperazine-l-carboxylic acid tert-butyl ester (58); [0284] To a solution of 4-bromo-benzenesulfonyl chloride (1.0 g, 3.9 mmol) and piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 5.4 mmol) in dry DCM (15 mL) was added triethylamine (1.6 mL, 11 mmol). The reaction mixture was stirred at room temperature for 2.5 h and then diluted with EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over MgSθ4 and filtered. The filtrate was concentrated to afford the title compound, which was used in the next step without purification.
With triethylamine In dichloromethane at 20℃; for 48h;
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; 3 4-(4-Bromo-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester (L-31′) To a solution of 4-bromobenzenesulfonyl chloride L-31′ (1.000 g; 3.914 mmol) in DCM (10.0 mL), piperazine-1-carboxylic acid tert-butyl ester (0.729 g; 3.914 mmol) and DIPEA (1.347 mL; 7.827 mmol) are added and stirred at RT overnight. The reaction mixture is quenched with water and extracted with DCM (3×50.0 mL). The combined organic layers are dried over Na2SO4, filtered and concentrated under reduced pressure to give the expected product. (0896) HPLC-MS: (M+H-BOC)+=305;307; tRet=0.77 min; method M2
With triethylamine In dichloromethane

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  • 2
  • [ 3073-77-6 ]
  • [ 259808-63-4 ]
  • [ 910907-48-1 ]
YieldReaction ConditionsOperation in experiment
30% With potassium tert-butylate;palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; for 16h;Heating / reflux; Example 109. 4-f4-(5-Nitro-pyrimidin-2-ylaininoVbenzenesulfonvIl-piperazine-l- carboxylic acid tert-bntyl ester (59); [0285] A mixture of <strong>[3073-77-6]5-nitro-pyrimidin-2-ylamine</strong> (0.25 g, 1.8 mmol), compound 58 described in Example 108 (1.0 g, 2.5 mmol), Pd(OAc)2 (20 mg, 0.09 mmol), Xantphos (0.1 g, 0.17 mmol) and potassium tert-butoxide (0.40 g, 3.6 mmol) were suspended in dioxane (15 mL) and heated at reflux under the argon atmosphere for 16 h. The mixture was allowed to cool to room temperature, filtered and washed with DCM. The filtrate was concentrated and the residue triturated in DCM-Et2O (1 :5 v/v) and the solid filtered. The solid was washed with Et2O to afford the title compound (0.25 g, 30%) as an orange solid. The crude title compound was used in the next step without purification. MS (ES+): m/z 365 (M+H-Boc)+.
  • 3
  • [ 259808-63-4 ]
  • [ 73183-34-3 ]
  • [ 1042917-53-2 ]
YieldReaction ConditionsOperation in experiment
90% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 20℃; Inert atmosphere; 2 Step 2: tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzenesulfonyl]piperazine-1-carboxylate: To a solution of tert-butyl 4-(4-bromobenzenesulfonyl)piperazine-1-carboxylate (18 g, 44.41 mmol) in 1,4-dioxane (200 mL) were added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (34 g, 133.23 mmol), Pd(dppf)Cl2·CH2Cl2 (3.63 g, 4.44 mmol) and KOAc (8.72 g, 88.82 mmol) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for an additional 3 h at 90 oC. The resulting mixture was cooled down to room temperature, diluted with water (200 mL) and extracted with DCM (3 x 200 mL). The combined organic layers was washed with brine (200 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with 20%-50% ethyl acetate in petroleum ether to afford tert- butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonyl]piperazine-1- carboxylate (18 g, 90%) as a light pink solid. 1H NMR (400 MHz, CDCl3) d 7.98 (d, J = 7.7 Hz, 2H), 7.74 (d, J = 7.7 Hz, 2H), 3.51 (t, J = 5.1 Hz, 4H), 2.98 (t, J = 4.9 Hz, 4H), 1.42 (s, 9H), 1.27 (s, 12H). LC/MS (ESI, m/z): [(M + 23)]+ = 475.30.
64% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
63% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 80℃; for 3h; 2 Step 2-Tert-butyl 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl) piperazine-1-carboxylate To a solution of tert-butyl 4-(4-bromophenyl)sulfonylpiperazine-1-carboxylate (10.0 g, 24.7 mmol) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (18.8 g, 74.0 mmol) in dioxane (100 mL) was added Pd(dppf)Cl2 (1.81 g, 2.47 mmol) and KOAc (4.84 g, 49.4 mmol). The reaction mixture was stirred at 80° C. for 3 hours. On completion, the mixture was filtered, and the filter was concentrated in vacuo to give a residue. The residue was purified by flash silica gel chromatography (Ethyl acetate: Petroleum ether=1/1) to give the title compound (8.00 g, 63% yield) as a gray solid. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.0 Hz, 2H), 3.52 (t, J=4.8 Hz, 4H), 2.98 (t, J=4.8 Hz, 4H), 1.42 (s, 9H), 1.37 (s, 12H), LC-MS (ESI+) m/z 397.0 (M+H-56)+.
  • 4
  • [ 259808-63-4 ]
  • [ 5419-55-6 ]
  • [ 486422-54-2 ]
YieldReaction ConditionsOperation in experiment
70% With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 18h; Inert atmosphere; 1.3 Preparation of (4-((4-(tert-butoxycarbonyl)piperazin-1-yl)sulfonyl)phenyl)boronic acid (5): Under -78°C and nitrogen protection, triisopropyl borate (3.5mL, 15mmol) was added to the solution of compound 4 (2.1g, 5mmol) in anhydrous THF (50mL), and then n-butyllithium was added dropwise (10 mL, 16 mmol, 1.6M). The resulting mixture was stirred for 2 hours and then allowed to warm to room temperature and stirred for an additional 16 hours. Water (5mL) was added, and then stirred for 2h. The solvent was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 5 (1.3 g, 70%) as a white solid.
70% With n-butyllithium In tetrahydrofuran; water at -78 - 20℃; for 20h; Inert atmosphere; (4-((4-(Tert-butoxycarbonyl)piperazin-1-yl)sulfonyl)phenyl)boronic acid (6). Triisopropylborate (3.5 mL, 15 mmol) was addedto a solution of compound 5 (2.1 g, 5 mmol) in anhydrous THF(50 mL) at 78 C under an atmosphere of nitrogen followed by dropwise addition of n-butyllithium (10 mL, 16 mmol, 1.6 M). Theresulting mixture was stirred for 2 h and then allowed to reachroom temperature for another 16 h H2O (5 mL) was added followedby stirred for 2 h. The solvent was evaporated purified by silica gelcolumn chromatography to obtain compound 6 (1.3 g, 70%) as awhite solid. 1H NMR (500 MHz, CDCl3) d 7.95 (d, J 7.8 Hz, 2H), 7.71(d, J 7.7 Hz, 2H), 5.53 (s, 1H), 3.49 (s, 4H), 2.95 (s, 4H), 1.40 (s, 9H).
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