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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 93-91-4 |
Formula : | C10H10O2 |
M.W : | 162.19 |
SMILES Code : | CC(CC(C1=CC=CC=C1)=O)=O |
MDL No. : | MFCD00008786 |
InChI Key : | CVBUKMMMRLOKQR-UHFFFAOYSA-N |
Pubchem ID : | 7166 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-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 |
---|---|---|
85% | General procedure: Appropriate beta-diketone (100 mmol) was dissolved in anhydrous acetone (80 mL). Subsequently, anhydrous potassium carbonate (93 mmol) was added under inert. After stirring the solution for 5 min. at room temperature, methyl iodide (7.72 mL, 100 mmol) was added dropwise during 10 min. The reaction mixture was then refluxed for 12 h. Volatile components were distilled off, the residue was diluted with ether (100 mL) and precipitated solid was removed by suction. The filtrate was evaporated in vacuo and the residue was further purified. | |
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h; | To a mixture of the benzoylacetone (1a) (2.0 mmol) and iodomethane (2.2 mmol) in N,N-dimethylformamide (5.0 mL) was added K2CO3 (1.5 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 18 h. The reaction was then quenched with H2O (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine (30 mL), dried over MgSO4 , filtered, and concentrated (aspirator). The residue was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.7% | With hydrazine; In ethanol; water; for 16h; | Hydraxine hydrate (9.0 mL, 99 mmol, 35 wt.% in HaO; 0.64 equiv) isadded to a solution of benzoylacetone (25.00 g, 154.1 mmol, 1 equiv) in ethanol(250 mL). After stirring 14 h, more hydrazine hydrate (8.0 mL, 88 mmol, 0.57 equiv) isadded. After 2 h, the reaction solution is concentrated (95 C) to give the title compoundas a white solid (24.31 g, 99.7%). HRMS Calculated for CioHnN2: m/z 159.0922. Found:159.0917 |
98% | With carbazic acid; In neat (no solvent); at 90℃; for 3h; | 1-phenylbutane-1, 3-dione (8.11 g) at 90 C for 3 hours. The remainder was the same as in Example 1. The obtained compound was 5-methyl-3-phenyl-1H-pyrazole, the selectivity was> 99%, and the yield was 98%. |
97% | With hydrazine; In ethanol; at 80℃; for 3h; | A compound wherein a methyl group was introduced into the 5-position of the pyrazole ring of XO-TT469 was synthesized. A pyrazole, XO-TT485, was prepare by condensation reaction of 1-phenyl-1,3-butanedione and hydrazine. And a 4-phenylcarboxylic acid unit was introduced (the following scheme).; XO-TT485; 1-phenyl-1,3-butanedione (2.00g, 12.3 mmol) was dissolved in ethanol, and to the solution was added hydrazine monohydrate (1.80 mL, 37.0 mmol), and the mixture was stirred at 80C for 3 hours. After about 80% of ethanol in the reaction solution was removed under reduced pressure, water (200 mL) was added to the residue. The precipitated solid was collected by filtration and dried in vacuo at 80C to give XO-TT485 as a white solid (1.88 g, 97% yield). |
92% | With sodium acetate; hydrazine hydrate; In acetic acid; at 70℃; for 18h; | 1-Phenylbutane-1,3-dione (4.76 g, 29.4 mmol) was dissolved in 20 ml acetic acid. Hydrazine monohydrate (1.0 g, 19.6 mmol) and sodium acetate (8.0 g, 98 mmol) were added and the mixture was stirred at 70C overnight. The mixture was partitioned between ethyl acetate and water. The aqueous was extracted three times with ethyl acetate. The organic layer was washed sequentially three times with dilute potassium carbonate solution and then with brine. The organics were dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified using the SP1 Purification System (ethyl acetate-hexane gradient, 0:100 rising to 30:70) to give 5-methyl-3-phenyl-1H-pyrazole (2.86 g, 18 mmol, 92%) as a pale yellow solid. |
75% | With titanium(IV) oxide; hydrazine; In neat (no solvent); at 60℃;Green chemistry; | General procedure: A mixture of 1,3-diketone (2 mmol), hydrazine derivatives (2mmol) and nano TiO2 (20%) was heated at 60 C. The progress of the reaction was monitored by TLC. After the completion of the reaction, the mixture was washed with chloroform and filtered to recover the catalyst. The filtrate was evaporated and the crude product was recrystallized from iso-propanol to afford the purepyrazoles derivatives in 75-92 % yields. |
With hydrazine hydrate; In ethanol; at 20℃; for 0.25h; | To a solution of 1-benzoylacetone (0.20 g, 1.23 mmol) in ethanol (1.2 mL) was added dropwise hydrazine (0.08 mL, 1.5 mmol) at rt. The resulting reaction mixture was stirred to rt for 15 min(reaction monitored by TLC and UPLC-MS). 1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; hydrazine; In dichloromethane; N,N-dimethyl-formamide; acetonitrile; | Step C]: [1,1-Dimethyl-3-(5-methyl-3-phenyl-pyrazol-1-yl)-propyl]-carbamic Acid Tert-Butyl Ester 5-Methyl-3-phenyl-1H-pyrazole (320 mg, prepared from benzoylacetone and hydrazine according to Ali et al., Pak. J. Sci. Ind. Res. 1993, 36 (12), 502) was dissolved in DMF (7 ml) and cooled to 0 C. with an ice bath. Potassium-tert-butoxide (284 mg) was added in portions and the mixture was stirred for 45 min at 0 C. Then, 4,4-dimethyl-2,2-dioxo-2lambda'-[1,2,3]oxathiazinane-3-carboxylic acid tert-butyl ester (617 mg) was added in one portion and the reaction mixture was allowed to stir for 20 hours at RT. HCl (1N aqueous solution, 10 ml) was added and stirring was continued for 15 minutes. The mixture was diluted with ether, washed with water and brine (the aqueous layers were re-extracted twice with ether), dried and evaporated. The crude product was purified by flash chromatography (0 to 15% gradient of CH3CN in CH2Cl2) to give the desired product as a yellow gum. Yield: 545 mg. A regioisomer present in minor amounts was removed in the chromatographic purification step. MS (ISP): 344.5 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With copper(l) chloride; In 1,2-dichloro-ethane; at 80℃; | In order to 1-phenyl-1,3-butanedione, tert-butyl peroxybenzoate is used as a raw material, the reaction steps are as follows:In the reaction flask by adding 1-phenyl-1,3-butanedione (0.16g, 1mmol), tert-butyl peroxybenzoate (0.97g, 5mmol), CuCl (0.01g, 0 . 1mmol) and 2mL1, 2-dichloroethane, 80 C reaction;TLC until the complete end tracking of the reaction;After the reaction the crude product by column chromatography (petroleum ether: ethyl acetate = 40:1), to obtain the target product (yield 72%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With formic acid; In methanol; at 20℃; for 1h;UV-irradiation; Inert atmosphere; | General procedure: Amino-styrene 2 (0.34 mmol, 1 equiv.), corresponding diketone (1.1 equiv.), and formic acid (0.01 equiv.) were dissolved in methanol in a round bottom flask. With the previous knowledge of concentration of enaminone required for the OD of 0.2 at the irradiation wavelength, the corresponding concentration of amino-styrene and 1,3-diketone was determined. At this concentration, the mixture of styrene amine 2a (1 equiv.) and 1,3 - diketone (1.1 equiv) in methanol was stirred in Pyrex test tube at room temperature for 2 h for the formation of enaminone. The completion of reaction for the enaminone formation was confirmed from crude 1H-NMR spectroscopy. The reaction mixture was dissolved in 120 mL of methanol and was transferred to 8 Pyrex test tubes and degassed with nitrogen for 15 min. It was followed by the irradiation in a Rayonet reactor with a light source of ~350 nm. Progress of the reaction was monitored by crude 1H-NMR spectroscopy of the reaction mixture. After the completion of the reaction, solvent was removed under the reduced pressure. The crude product was purified by chromatography (Combiflash) using ethyl acetate/hexanes mixture as mobile phase. For irradiation times and yields, refer to FIG.45. [00165] As noted above, FIGS.26A-26B show the NMR spectra of photoproduct 3a. Yield = 76%. 1H-NMR (500 MHz, CDCl3, δ ppm): 7.55 - 7.48 (m, 2H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 7.30 - 7.21 (m, 3H), 7.10 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 6.73 (td, J = 7.4, 1.1 Hz, 1H), 6.57 (dd, J = 8.0, 1.1 Hz, 1H), 5.36 (t, J = 2.7 Hz, 1H), 5.18 (d, J = 2.0 Hz, 1H), 4.20 (s, 1H), 2.18 (dd, J = 12.7, 2.9 Hz, 1H), 1.99 (dt, J = 12.7, 2.4 Hz, 1H), 1.51 (s, 3H). 13C-NMR (126 MHz, CDCl3, δ ppm): 151.4, 145.4, 135.5, 131.1, 129.6, 128.4, 128.2, 125.2, 122.1, 118.2, 115.4, 104.9, 71.4, 46.5, 35.0, 27.3. HRMS-ESI (m/z) ([M + H]+): Calculated: 264.1388; Observed: 264.1396; |Δm| = 3.0 ppm. |
64% | With formic acid; In methanol; at 20℃; for 1h;UV-irradiation; Inert atmosphere; | General procedure: Amino-styrene 2 (0.34 mmol, 1 equiv.), corresponding diketone (1.1 equiv.), and formic acid (0.01 equiv.) were dissolved in methanol in a round bottom flask. With the previous knowledge of concentration of enaminone required for the OD of 0.2 at the irradiation wavelength, the corresponding concentration of amino-styrene and 1,3-diketone was determined. At this concentration, the mixture of styrene amine 2a (1 equiv.) and 1,3 - diketone (1.1 equiv) in methanol was stirred in Pyrex test tube at room temperature for 2 h for the formation of enaminone. The completion of reaction for the enaminone formation was confirmed from crude 1H-NMR spectroscopy. The reaction mixture was dissolved in 120 mL of methanol and was transferred to 8 Pyrex test tubes and degassed with nitrogen for 15 min. It was followed by the irradiation in a Rayonet reactor with a light source of ~350 nm. Progress of the reaction was monitored by crude 1H-NMR spectroscopy of the reaction mixture. After the completion of the reaction, solvent was removed under the reduced pressure. The crude product was purified by chromatography (Combiflash) using ethyl acetate/hexanes mixture as mobile phase. For irradiation times and yields, refer to FIG.45. [00165] As noted above, FIGS.26A-26B show the NMR spectra of photoproduct 3a. Yield = 76%. 1H-NMR (500 MHz, CDCl3, δ ppm): 7.55 - 7.48 (m, 2H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 7.30 - 7.21 (m, 3H), 7.10 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 6.73 (td, J = 7.4, 1.1 Hz, 1H), 6.57 (dd, J = 8.0, 1.1 Hz, 1H), 5.36 (t, J = 2.7 Hz, 1H), 5.18 (d, J = 2.0 Hz, 1H), 4.20 (s, 1H), 2.18 (dd, J = 12.7, 2.9 Hz, 1H), 1.99 (dt, J = 12.7, 2.4 Hz, 1H), 1.51 (s, 3H). 13C-NMR (126 MHz, CDCl3, δ ppm): 151.4, 145.4, 135.5, 131.1, 129.6, 128.4, 128.2, 125.2, 122.1, 118.2, 115.4, 104.9, 71.4, 46.5, 35.0, 27.3. HRMS-ESI (m/z) ([M + H]+): Calculated: 264.1388; Observed: 264.1396; |Δm| = 3.0 ppm. |