Structure of 960388-56-1
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CAS No. : | 960388-56-1 |
Formula : | C12H16BClO3 |
M.W : | 254.52 |
SMILES Code : | OC1=CC(B2OC(C)(C)C(C)(C)O2)=CC(Cl)=C1 |
MDL No. : | MFCD12546581 |
InChI Key : | MJTRKHGZBSKPKX-UHFFFAOYSA-N |
Pubchem ID : | 46739674 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P330-P363-P501 |
* 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 |
---|---|---|
28% | With water; potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 150℃; for 0.25h; | 3-Bromo-5-chlorophenol (5 g, 19.9 mmol, described in: Maleczka R. E. et. al. J. Am. Chem. Soc. 2003, 125, 7792-7793), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (6.06 g, 23.9 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (487 mg, 0.6 mmol), potassium acetate (5.86 g, 59.7 mmol), 1,2-dimethoxyethane (60 mL) and water (4 mL) were divided into four microwave vials and irradiated in a microwave at 150 C. for 15 min each. When cooled to ambient temperature the mixtures were pooled, diluted with brine and extracted with diethyl ether. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Purified by column chromatography, using a gradient with 0-5% acetonitrile in dichloromethane as the eluent, to give 1.43 g (28% yield) of the title compound: 1H NMR (DMSO-d6) δ 9.89 (s, 1H), 7.02 (s, 2H), 6.91 (s, 1H), 1.28 (s, 12H); MS (ES) m/z 253 [M-H]-. |
28% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 150℃; for 0.25h;Irradiation in a microwave; | 3-Bromo-5-chlorophenol (5 g, 19.9 mmol, described in: Maleczka R. E. et. al. J. λ(rø. Chem. Soc. 2003, 725, 7792-7793), 454,4',4',5,5,5l,5I-octamethyl-2,2'-bi-l>3,2- dioxaborolane (6.06 g, 23.9 mmol), [l,r-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (487 mg, 0.6 mmol), potassium acetate (5.86 g, 59.7 mmol), 1,2-dimethoxyethane (60 mL) and water (4 mL) were divided into four microwave vials and irradiated in a microwave at 150 C for 15 min each. When cooled to room temperature the mixtures were pooled, diluted with brine and extracted with diethyl ether. The combined organics were dried over sodium sulfate and concentrated in vacuo. Purified by column chromatography, using dichloromethane/acetonitrile (95:5) as the eluent, to give 1.43 g (28% yield) of the title compound: 1H NMR (DMSO-^6) δ 9.89 (s, 1 H) 7.02 (s, 2 H) 6.91 (s, 1 H) 1.28 (s, 12 H); MS (ESI) m/z 253 [M-H] |
28% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 150℃; for 0.25h;Microwave irradiation; | Example 5 3-Chloro-5-(4A5,5-tetramethyl-1.3.2-dioxaborolan-2-yl)phenol; 3-Bromo-5-chlorophenol (5 g, 19.9 mmol, described in: Maleczka R. E. et. al. J. Am. Chem. Soc. 2003, 125, 7792-7793), 4,4,4',4',5,5,51,51-octamethyl-2,2'-bi-l,3,2- dioxaborolane (6.06 g, 23.9 mmol), [l,r-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (487 mg, 0.6 mmol), potassium acetate (5.86 g, 59.7 mmol), 1 ,2-dimethoxyethane (60 mL) and water (4 mL) were divided into four microwave <n="50"/>vials and irradiated in a microwave at 150 C for 15 min each. When cooled to ambient temperature the mixtures were pooled, diluted with brine and extracted with diethyl ether. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Purified by column chromatography, using a gradient with 0-5% acetonitrile in dichloromethane as the eluent, to give 1.43 g (28% yield) of the title compound: 1H NMR (DMSOd6) δ 9.89 (s, 1 H), 7.02 (s, 2 H), 6.91 (s, 1 H), 1.28 (s, 12 H); MS (ES) m/z 253 [M-I]-. |
28% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 150℃; for 0.25h;Microwave irradiation; | Example 5; 3-Chloro-5-f4.4.5.5-tetramethvl-1.3.2-dioxaborolan-2-vDphenol/ cr ^ OH; 3-Bromo-5-chlorophenol (5 g, 19.9 mmol, described in: Maleczka R. E. et. al. J. Am.Chem. Soc. 2003, 125, 7792-7793), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi~l,3,2- dioxaborolane (6.06 g, 23.9 mmol), [l,r-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (487 mg, 0.6 mmol), potassium acetate (5.86 g, 59.7 mmol), 1,2-dimethoxyethane (60 mL) and water (4 mL) were divided into four microwave vials and irradiated in a microwave at 150 C for 15 min each. When cooled to ambient temperature the mixtures were pooled, diluted with brine and extracted with diethyl ether.The combined organic phases were dried over sodium sulfate and concentrated in vacuo.Purified by column chromatography, using a gradient with 0-5% acetonitrile in dichloromethane as the eluent, to give 1.43 g (28% yield) of the title compound: 1H NMR(DMSO-J6) δ 9.89 (s, 1 H), 7.02 (s, 2 H), 6.91 (s, 1 H), 1.28 (s, 12 H); MS (ES) m/z 253[M-I]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethylamine; In dichloromethane; at 0 - 20℃; for 1h; | Methanesulfonyl chloride (122 μL, 0.79 mmol) was added drop wise at 0 C. to a mixture of <strong>[960388-56-1]3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol</strong> (200 mg, 0.79 mmol) and triethylamine (0.4 mL, 3.14 mmol) in dry dichloromethane (1.5 mL). The reaction mixture was stirred for 1 h at ambient temperature, diluted with dichloromethane (10 mL), washed with water, dried over sodium sulfate and concentrated in vacuo to give 0.200 g (86% yield) of the crude title compound: 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J=1.52 Hz, 2H), 7.57 (d, J=1.77 Hz, 2H), 7.41 (t, J=2.15 Hz, 1H), 3.18 (s, 3H), 1.35 (s, 12H); MS (EI) m/z 332 [M+]. |
86% | With triethylamine; In dichloromethane; at 20℃; for 1h; | Methanesulfonyl chloride (122 μL, 0.79 mmol) was added dropwise to a cooled (0 0C) mixture of 3-chloro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenol (200 mg, 0.79 mmol) and triethylamine (0.4mL, 3.14 mmol) in anhydrous dichloromethane (1.5 mL). The <n="116"/>reaction mixture was allowed to reach room temperature and stirred for 1 h. Dichloromethane (10 mL) was added and the organic phase was washed with water, dried over sodium sulfate and concentrated in vacuo to give 200 mg (86% yield) of the crude title compound: 1H NMR (CDCl3) δ 7.75 (d, J= 1.5 Hz, 2 H), 7.57 (d, J= 1.8 Hz, 2 H)3 7.41 (t, J= 2.1 Hz, 1 H), 3.18 (s, 3 H), 1.35 (s, 12 H); GC-MS (EI) m/z 332 [M]+. |
86% | With triethylamine; In dichloromethane; at 0 - 20℃; for 1h; | Example 6 3-Chloro-5-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)phenyl methanesulfonate; Methanesulfonyl chloride (122 μL, 0.79 mmol) was added dropwise at 0 0C to a mixture of 3-chloro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenol (200 mg, 0.79 mmol) and triethylamine (0.4 mL, 3.14 mmol) in dry dichloromethane (1.5 mL). The reaction mixture was stirred for 1 h at ambient temperature, diluted with dichloromethane (10 mL), washed with water, dried over sodium sulfate and concentrated in vacuo to give 0.200 g (86% yield) of the crude title compound: 1H NMR (CDCl3) 5 7.75 (d, J= 1.52 Hz, 2 H), 7.57 (d, J= 1.77 Hz, 2 H), 7.41 (t, J= 2.15 Hz, 1 H), 3.18 (s, 3 H), 1.35 (s, 12 H); GC-MS (EI) m/z 332 [M]+. |
86% | With triethylamine; In dichloromethane; at 20℃; for 1h; | Example 6; 3 -Chloro-5 -(4,4,5,5 -tetramethyl- 1 ,3 ,2-dioxaborolan-2-vDρhenvl methanesulfonate; <n="49"/>/ Tcr Methanesulfonyl chloride (122 μL, 0.79 mmol) was added dropwise at 0 C to a mixture of 3-chloro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenol (200 mg, 0.79 mmol) and triethylamine (0.4 mL, 3.14 mmol) in dry dichloromethane (1.5 mL). The reaction mixture was stirred for 1 h at ambient temperature after which it was diluted with dichloromethane (10 mL), washed with water, dried over sodium sulfate and concentrated in vacuo to give 0.200 g (86% yield) of the crude title compound: 1H NMR (CDCl3) δ 7.75 (d, J= 1.52 Hz, 1 H), 7.57 (d, J= 1.77 Hz, 1 H), 7.41 (t, J= 2.15 Hz, 1 H), 3.18 (s, 3 H), 1.35 (s, 12 H); MS (EI) m/z 332 [M+*]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; for 0.166667h; | 3-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (200 mg, 0.79 mmol) in tetrahydrofuran (dry, 1.5 mL) was added drop wise to a slurry of sodium hydride in tetrahydrofuran (dry, 0.5 mL). The mixture was stirred for 10 min and iodomethane (147 μL, 2.36 mmol) was added. The obtained mixture was stirred overnight. Saturated aqueous ammonium chloride (1 mL) was added and the product was extracted with dichloromethane (20 mL). The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to give 0.170 g (90% yield) of the crude title compound: 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J=1.26 Hz, 1H), 7.20 (d, J=2.02 Hz, 1H), 7.02-6.98 (m, 1H), 3.83 (s, 3H), 1.35 (s, 12H); MS (EI) m/z 268 [M+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
177 mg | To a solution of 1-indan-2-yl-3-iodo-pyrazolo[3,4-d]pyrimidin-4-amine (300 mg, 0.795 mmol) and 3-chloro-5- (4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenol (304 mg,1.193 mmol) in DMF (5 mL) was added a solution of sodium carbonate (253 mg, 2.387 mmol) in water (5 mL) followed by the addition of tetrakis(triphenylphosphine)palladium(0) (92 mg, 0.0795 mmol). The reaction mixture was heated in a reagent bottle at 100 C for 2 h. The reaction was monitored by TLC. After completion of reaction, water (45 mL) was added to the reaction mixture and the product was extracted with EtOAc (2x 100 mL). The combined organic layer was again washed with water (100 mL) and finally with brine solution (2x75 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude product which was purified by reverse phase HPLC to give 3- (4-amino-i -indan-2-yl-pyrazolo [3 ,4-d]pyrimidin-3-yl)-5- chloro-phenol (175 mg) as an off-white solid, which was dissolved in 10 mL ethanolic HC1 and concentrated under reduced pressure to 3-(4-amino-i-indan-2-yl-pyrazolo[3,4- d]pyrimidin-3-yl)-5-chloro-phenol (177 mg) off-white solid. NMR (400 MHz, Methanol-d4) ö (ppm): 8.42 (s, 1H), 7.31 -7.24 (m, 2H), 7.21 (dd, I = 5.6, 3.3 Hz, 2H), 7.14 (t, I = 1.7 Hz, 1H), 6.99 (dt, I = 17.0, 2.0 Hz, 2H), 5.86 (p, I = 8.2 Hz, 1H), 3.62 (dd, I = 15.9, 7.5 Hz, 2H),3.53 (dd, I = 16.0, 8.3 Hz, 2H). LCMS: 378 (M+i). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
into a flask and washed twice with n-heptane (1 ml). Dry THF (1.00 ml)was added, followed by a solution of compound 1 (<strong>[960388-56-1]3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol</strong>) (33.5 mg, 132 mmol) in dryTHF (0.50 ml). The mixture was allowed to stir for 20 minutes at roomtemperature under a nitrogen atmosphere, at which time a solution ofC3H3I (400mCi, 6.5 mmol) in dry THF (0.5 ml) was added. The reactionmixture was stirred at room temperature for 36 hours before beingdiluted with dichloromethane (1.0 ml) and filtered through celite.The clear organic solution was concentrated to provide compound 2 (2-(3-chloro-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [5-methoxy-C3H3]), which was subsequently dissolved in 1,4-dioxane(0.2 ml). To this solution was added Cs2CO3 (11.8 mmol, 36.2 mmol),CuCl (2.68 mg, 27.1 mmol), compound 3* ((P)-1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide) (4.91 mg, 9.93 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.92 mg,2.71 mmol). The mixture was stirred at 50C for 5 hours. The reactionwas cooled to room temperature, filtered through celite and washedwith MeOH (10 ml). The filtrate was concentrated under reducedpressure, and the residuewas purified by preparative high-performanceliquid chromatography [Waters (Milford, MA) X-Bridge C18 Column;10.0 150 mm, 5 mm; mobile phase A 0.1% trifluoroacetic acid (TFA)water; mobile phase B 0.1% TFA acetonitrile; gradient: (minimum,B%)5(0, 40)→(20, 100)→(25, 100)→(25.1, 40)→(30, 40) ; 5.0ml/min,254 nm] to afford a solution of compound 4. To the derived solution wasadded saturated aqueousNaHCO3 (0.1 ml), and themixture was loadedonto a BAKERBOND SPE C18 cartridge (6 ml, 500 mg; catalog7020-06; J.T.Baker, Phillipsburg, New Jersey). The cartridge was rinsedwith water, and then the desired product was elutedwith ethanol to providecrude compound 4. This material was subsequently repurified via chiralpreparative high-performance liquid chromatography (4.6 250 mm,5 mm; mobile phase: TFA/n-heptane/EtOH 5 0.2/75/25; 1.0 ml/min;254nm; CHIRALCEL OD-H; Chiral Technologies Europe SAS, Illkirch,France). The combined fractions containing compound 4 were treatedwith saturated aqueousNaHCO3 (0.1ml). Thismixturewas loaded ontoa BAKERBOND SPE C18 Cartridge (6 ml, 500 mg; catalog 7020-06).The cartridge was rinsed with water, and then the desired productwas eluted with ethanol to provide ((P)-1-(3-chloro-2-fluoro-5,5-dimethoxy-[1,1-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide [5-methoxy-C3H3]) as a white solid [185 MBq (5.0 mCi),37 MBq (1.0 mCi) in EtOH]. Radioligand 4 corresponds to tritiatedcompound 501, and intermediate 3 corresponds to :Intermediate BN:from the study by Weiss et al. (2014) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; for 3h;Reflux; | Combine S2 (30mmol), 2-chloro-4-phenylquinazoline (60mmol), potassium carbonate (45mmol), dioxane (200mL), tetrakis (triphenylphosphine) palladium (0.3mmol), water 50mL Add to the reaction flask, heat to reflux and react for 3 hours. TLC monitors the completion of the reaction. The reaction solution is poured into water and filtered. After extraction with dichloromethane, it is concentrated and recrystallized with toluene to obtain Intermediate A. |
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