Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 18931-60-7 | MDL No. : | MFCD00511276 |
Formula : | C10H6ClF3O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LJHFYVKVIIMXQM-UHFFFAOYSA-N |
M.W : | 250.60 | Pubchem ID : | 2773832 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.2 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 51.65 |
TPSA : | 34.14 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.56 cm/s |
Log Po/w (iLOGP) : | 1.62 |
Log Po/w (XLOGP3) : | 3.2 |
Log Po/w (WLOGP) : | 4.3 |
Log Po/w (MLOGP) : | 2.36 |
Log Po/w (SILICOS-IT) : | 3.64 |
Consensus Log Po/w : | 3.03 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.42 |
Solubility : | 0.0946 mg/ml ; 0.000377 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.59 |
Solubility : | 0.0646 mg/ml ; 0.000258 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.21 |
Solubility : | 0.0156 mg/ml ; 0.0000621 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.46 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
55% | With potassium fluoride; hexafluoropropene-diethylamine adduct In acetonitrile for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With calcium sulfate; 4-methyl-3-nitrobenzenesulfanyl azide In dichloromethane for 24h; | |
31% | With aluminum oxide; potassium fluoride; 4-toluenesulfonyl azide In pentane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: ethyl trifluoroacetate, With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: para-chloroacetophenone In tetrahydrofuran for 2h; Reflux; | |
86% | Stage #1: ethyl trifluoroacetate,; para-chloroacetophenone With sodium methylate In methanol; tert-butyl methyl ether for 16h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; tert-butyl methyl ether; water | 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-carboxyamide The title compound was synthesized via a two-step synthesis. Step a. The preparation of 4,4,4-trifluoro-1-(4-chlorophenyl)butane-1,3-dione was carried out as follows. To a solution of ethyl trifluoroacetate (1.08 g, 7.61 mmol) in 5 mL of methyl tert-butyl ether (MTBE) was added 25% sodium methoxide in methanol (1.8 mL)2 min. A solution of 4'-chloroacetophenone (1 g, 6.46 mmol) in 2 mL MTBE was added to the mixture dropwise5 min. After stirring for 16 h, 3 N HCl (3.4 mL) was added. The organic layer was collected, washed with brine, driedmagnesium sulfate, and concentrated to give a yellow-orange solid. Recrystallization from hexane yielded the dione (1.18 g, 86%). Step b. (4-Carbamoylphenyl)hydrazine hydrochloride (228 mg, 1.21 mmol) was added to a stirred solution of the aforementioned dione (300 mg, 1.21 mmol) in 20 mL of ethanol. The mixture was stirred under reflux for 24 h, cooled to room temperature, and concentrated to dryness. The residue was dissolved in ethyl acetate, washed with brine, driedmagnesium sulfate, and concentrated to give a light brown solid. Recrystallization from ethyl acetate and hexane gave the title compound (350 mg, 80%): 1H NMR (CDCl3) δ {tilde()}s, 1H), 7.16 (d, J=8.5 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 7.83 (d, J=8.4 Hz, 2H); HRMS calc'd for M+ 365.0535, found 365.0522. Anal. (C17H11ClF3N3O)C, H, N. |
86% | With sodium methylate In ethanol at 20℃; for 3h; | General procedure for the synthesis of substituted diketones 3bd(3d as example): General procedure: 40-chloroacetophenone (0.50 mL, 3.86 mmol)was added to a solution of ethyl trifluoroacetate (0.5 mL,4.20 mmol) containing 5.4M sodium methoxide (0.8 mL,4.60 mmol) in ethanol (8.0 mL). The reaction mixture was stirred atroom temperature for 3 h, after which the mixturewas diluted withcold water and 2 N HCl (5.0 mL). The resulting mixture was left tostand overnight to obtain a precipitate. The precipitatewas filtered,washed with cold water and air dried to give the pure compound. |
85% | With sodium methylate In methanol for 15.75h; | |
85% | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1 Step 1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). 4'-Chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL) and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a yellow-orange solid. The solid was recrystallized from isooctane to give the dione (31.96 g, 85%): mp 66-67° C. |
85% | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1: Step 1: Preparation of 4.4.4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). 4'-Chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL) and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a yellow-orange solid. The solid was recrystallized from isooctane to give the dione (31.96 g, 85%): mp 66-67° C. |
85% | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide Step 1: Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione. Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). 4'-Chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL) and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a yellow-orange solid. The solid was recrystallized from isooctane to give the dione (31.96 g, 85%): mp 66-67° C. |
85% | With sodium methylate In tert-butyl methyl ether for 15.75h; | 1.1 Step 1: Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione. Step 1: Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione. ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 ML).. To the stirred solution was added 25 weight % sodium methoxide (40 ML, 177 mmol).. Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 ML), and added to the reaction dropwise.. After stirring overnight (15.75 hours), 3N HCl (70 ML) was added.. The organic layer was collected, washed with brine (75 ML), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid.. The solid was recrystallized from isooctane to give 31.96 g (85%) of the dione: mp 66-67 ° C. |
85% | With sodium methylate In tert-butyl methyl ether for 15.75h; | 1 Ethyl trifluoroacetate (23.52 g, 166 mmol) was placed in a 500 mL three-necked round bottom flask, and dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol) via an addition funnel over a 2 minute period. Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise over 5 minutes. After stirring overnight (15.75 hours), 3N HCI (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from iso-octane to give 31.96 g, 85% of the dione mp 660-67° C. |
83% | With potassium <i>tert</i>-butylate In benzene for 15h; Ambient temperature; | |
75% | Stage #1: para-chloroacetophenone With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at 0 - 25℃; for 12h; | |
Stage #1: para-chloroacetophenone With sodium hydride In N,N-dimethyl-formamide at -5 - 0℃; for 0.5h; Stage #2: ethyl trifluoroacetate, In N,N-dimethyl-formamide at 20℃; for 5h; | ||
With sodium methylate In 1,2-dimethoxyethane at 20℃; | ||
31.96 g (85%) | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid Step 1: Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione. Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from isooctane to give 31.96 g (85%) of the dione: mp 66-67° C. |
31.96 g (85%) | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1 Step 1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from isooctane to give 31.96 g (85%) of the dione: mp 66-67° C. |
With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1 Step 1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was placed in a 500 mL three-necked round bottom flask, and dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol) via an addition funnel over a 2 minute period. Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise over 5 minutes. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from iso-octane to give 31.96 g, 85% of the dione, mp 66°-67° C. | |
With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Step 1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25 weight % sodium methoxide (40 mL, 177 mmol). Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from isooctane to give 31.96 g, 85% of the dione, mp 66°-67° C. | |
31.96 g (85%) | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1 Step 1 Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was placed in a 500 mL three-necked round bottom flask, and dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25% sodium methoxide (40 mL, 177 mmol) via an addition funnel over a 2 minute period. Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise over 5 minutes. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from iso-octane to give 31.96 g (85%) of the dione: mp 66°-67° C. |
31.96 g (85%) | With hydrogenchloride; sodium methylate In tert-butyl methyl ether | 1.1 Step 1: Step 1: Preparation of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione Ethyl trifluoroacetate (23.52 g, 166 mmol) was placed in a 500 mL three-necked round bottom flask, and dissolved in methyl tert-butyl ether (75 mL). To the stirred solution was added 25% sodium methoxide (40 mL, 177 mmol) via an addition funnel over a 2 minute period. Next 4'-chloroacetophenone (23.21 g, 150 mmol) was dissolved in methyl tert-butyl ether (20 mL), and added to the reaction dropwise over 5 minutes. After stirring overnight (15.75 hours), 3N HCl (70 mL) was added. The organic layer was collected, washed with brine (75 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a 35.09 g of yellow-orange solid. The solid was recrystallized from iso-octane to give 31.96 g (85%) of the dione: mp66°-67° C. |
With sodium hydride | ||
With sodium methylate In methanol at 20℃; for 19h; | I.1; A.1.1 Step 1: To a stirred solution of compound of formula (I) (either commercially available or prepared as described hereinafter) in an organic solvent (e.g. tert-butyl-methyl-ether) is added at room temperature a solution of sodium methanolate in methanol followed by a solution of a compound of formula (II) in an organic solvent (e.g. tert-butyl-methyl-ether). The reaction mixture is stirred at room temperature for about 19 h, cooled, acidified and extracted (e.g. with diethyl ether). The combined organic layers are washed and dried (e.g. MgSO4) and evaporated to give crude the compound of formula (III) which can be used without further purification.; EXAMPLE A.12-Chloro-4-(4-chloro-phenyl)-6-trifluoromethyl-pyrimidine1) 4-(4-Chloro-phenyl)-6-trifluoromethyl-1H-pyrimidin-2-one: The compound was prepared from commercially available ethyl trifluoroacetate, commercially available 4-chloro-acetophenone and urea according to the general procedure I. Obtained as a light yellow solid (60%). MS (EI) 274.1 [(M)+]; mp 200° C. | |
Stage #1: ethyl trifluoroacetate, With potassium <i>tert</i>-butylate In diethyl ether at 20℃; for 0.75h; Stage #2: para-chloroacetophenone In diethyl ether | ||
With sodium hydride | ||
With sodium methylate In methanol for 2h; Reflux; | General Synthetic Procedure for 4,4,4-Trifluoro-1-phenylbutane-1,3-dione Compounds II General procedure: Referring to Scheme 1, to the appropriate acetophenone derivative (0.05 mol) and ethyltrifluoroacetate (0.075 mol) in methanol (20 mL), sodium methoxide solution (0.1 mol of Na + 15 mL ofCH3OH) was added dropwise at room temperature, and the mixture was refluxed for 2 h. After themethanol was evaporated under vacuum, the residue was dissolved in ethyl acetate (50 mL), washedwith 5% HCl (25 mL) and water (25 mL), and dried over sodium sulfate. After the solvent wasevaporated under vacuum, the corresponding compound II was obtained. | |
With sodium ethanolate In benzene | ||
Stage #1: para-chloroacetophenone With sodium hydride In tetrahydrofuran Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at 0 - 20℃; for 24h; | ||
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In ethanol for 20h; Heating; | |
In ethanol for 20h; Heating / reflux; | 2 4-Sulphonamidophenyl hydrazine hydrochloride (982 mg, 4.4 mmol 1.1 equivalent) was added to a stirred solution of 4,4,4-trifluoro-1-[4-(chloro)phenyl]-butane-1,3-dione (1.00 g, 4.0 mmol) in ethanol (50 mL). The reaction was heated to reflux and stirred for 20 hours. (HPLC area percent showed a 96:3 ratio of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide to its regioisomer (4-[3-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide). After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was taken up in ethyl acetate and washed with water and brine and dried over MgSO4, filtered, and concentrated in vacuo to give a light brown solid which was recrystallized from ethyl acetate and iso-octane to give the pyrazole 2, 1.28 g, 80% yield, mp 143°-145° C. HPLC showed that the purified material was a 99.5:0.5 mixture of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide to its regioisomer. 1H NMR (CDCl3/CD3OD 10/1) d 5.2 (s, 2H), 6.8 (s, 1H), 7.16 (d, j=8.5 Hz, 2H), 7.35 (d, j=8.5 Hz, 2H), 7.44 (d, j=8.66, 2H), 7.91 (d, j=8.66, 2H); 13C NMR (CDCl3/CD3OD 10/1) d 106.42 (d, j=0.03 Hz), 121.0 (q, j=276 Hz), 125.5, 1.26.9, 127.3, 129.2, 130.1, 135.7, 141.5, 143.0,143.9 (q, j=37 Hz), 144.0; 19F NMR (CDCl3/CD3OD 10/1) d-62.9. El GC-MS M+=401. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With ammonium acetate In Triethylene glycol dimethyl ether for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium fluoride In isopropyl alcohol for 10h; Heating; | |
82% | With piperidine at 20℃; for 16 - 24h; Heating / reflux; | I.a.1.a; A.16.1 Step 1 protocol a (R1 is CF3): To a mixture of a 1,3-diketo-compound of formula III (wherein R1 is CF3; prepared as described under general procedure I step 1) and cyanoacetamide in a protic solvent (e.g. ethanol) is added at room temperature a catalytic amount (ca. 0.1 eq.) of piperidine and the mixture stirred at reflux temperature for 16 to 24 h. The reaction mixture is concentrated in vacuum, then treated with ice-water and acidified with 1M aqueous hydrochloric acid to achieve pH 1, the precipitate is filtered off, washed with water and dried in air at 60 to 70° C. to give the crude compounds of formula XVI, which can be used without further purification (according to Org. Prep. Proced. Int. 1993, 25(1), 116-117).; EXAMPLE A.162-Chloro-6-(4-chloro-phenyl)-4-trifluoromethyl-pyridine1) 6-(4-Chloro-phenyl)-2-oxo-4-trifluoromethyl-1,2-dihydro-pyridine-3-carbonitrile: The compound was prepared from commercially available ethyl trifluoroacetate, commercially available 4-chloro-acetophenone and commercially available cyanoacetamide according to the general procedure I step 1 and Ia step 1. Obtained as a yellow solid (82%). MS (ISP) 299.1 [(M+H)+] and 301 [(M+2+H)+]; mp 287° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In various solvent(s) at 20℃; for 0.75h; | |
72% | In ethanol for 3h; Heating; | |
With sulfuric acid In ethanol regioselective reaction; |
With sulfuric acid In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride for 40h; Heating / reflux; | I.2; A.1.1 Step 2: To a stirred solution of a compound of formula III (1 eq) and urea (2 eq) in an organic solvent (e.g. MeOH) is added conc. HCl (e.g. MeOH/HCl 10:1). The reaction mixture is heated under reflux conditions for about 40 h, water is added and the mixture is stirred at 0° C. for 1 h. The precipitate is collected by filtration, washed with water and recrystallized (e.g. diethyl ether/hexane) to yield the compound of formulae IVa.; EXAMPLE A.12-Chloro-4-(4-chloro-phenyl)-6-trifluoromethyl-pyrimidine1) 4-(4-Chloro-phenyl)-6-trifluoromethyl-1H-pyrimidin-2-one: The compound was prepared from commercially available ethyl trifluoroacetate, commercially available 4-chloro-acetophenone and urea according to the general procedure I. Obtained as a light yellow solid (60%). MS (EI) 274.1 [(M)+]; mp 200° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With hydrogenchloride; sodium nitrile; sodium acetate In ethanol cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With hydroxylamine hydrochloride; sodium acetate In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In methanol at 20 - 25℃; | |
49% | In isopropyl alcohol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 80 percent / ethanol / 20 h / Heating 2: 75 percent / Cl2, AcOH / 1.25 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In ethanol for 24h; Heating / reflux; | 30b 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-carboxyamide (30b) The title compound was synthesized via a two-step synthesis. Step a. The preparation of 4,4,4-trifluoro-1-(4-chlorophenyl)butane-1,3-dione was carried out as follows. To a solution of ethyl trifluoroacetate (1.08 g, 7.61 mmol) in 5 mL of methyl tert-butyl ether (MTBE) was added 25% sodium methoxide in methanol (1.8 mL)2 min. A solution of 4'-chloroacetophenone (1 g, 6.46 mmol) in 2 mL MTBE was added to the mixture dropwise5 min. After stirring for 16 h, 3 N HCl (3.4 mL) was added. The organic layer was collected, washed with brine, driedmagnesium sulfate, and concentrated to give a yellow-orange solid. Recrystallization from hexane yielded the dione (1.18 g, 86%). Step b. (4-Carbamoylphenyl)hydrazine hydrochloride (228 mg, 1.21 mmol) was added to a stirred solution of the aforementioned dione (300 mg, 1.21 mmol) in 20 mL of ethanol. The mixture was stirred under reflux for 24 h, cooled to room temperature, and concentrated to dryness. The residue was dissolved in ethyl acetate, washed with brine, driedmagnesium sulfate, and concentrated to give a light brown solid. Recrystallization from ethyl acetate and hexane gave the title compound (350 mg, 80%): 1H NMR (CDCl3) δ {tilde()}s, 1H), 7.16 (d, J=8.5 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 7.83 (d, J=8.4 Hz, 2H); HRMS calc'd for M+ 365.0535, found 365.0522. Anal. (C17H11ClF3N3O)C, H, N. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In acetic acid for 3.5h; Heating / reflux; | 4.1 Example 4: Preparation of 5-phenyl-3-pyridinyl-7-trifluoromethyl-pyrazolo [1, 5- a] pyrimidines (General Procedure B); A stirred mixture of a 3-amino-4-pyridinyl-pyrazole (1 eq. ) and a 1-phenyl-4, 4,4- trifluoro-butane-1, 3-dione (1 eq. ), prepared according to general procedure A, in acetic acid was heated under reflux conditions for 3.5 h. The reaction mixture was evaporated and the product was isolated by column chromatography (heptane/ethyl acetate) and further purified by crystallization. If the product precipitates during the reaction it can be isolated by filtration and further purified by crystallization; Example 4.1; 5- (4-Chloro-phenyl)-3-pyridin-3-yl-7-trifluoromethyl-pyrazolo [1,5-a] pyrimidine; Reaction of 1- (4-chloro-phenyl)-4, 4, 4-trifluoro-butane-1, 3-dione (251 mg, 1.0 mmol), prepared from commercially available 4-chloro-acetophenone according to general procedure A, and 3-amino-4- (3-pyridinyl)-pyrazole [CAS No. 40545-68-2; prepared from 3-cyanomethyl-pyridine as described in Bioorg. Med. Chem. Lett. 12 (2002) 3537- 3541] (160 mg, 1.0 mmol) according to general procedure B yielded the title compound as a yellow solid (306 mg, 82%). MS (ISP) 375.3 [(M+H) +] ; mp 188°C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuryl dichloride In chloroform | 6 2-Chloro-1-(4'-chlorophenyl)-4,4,4-trifluorobuta-1,3-dione 2-Chloro-1-(4'-chlorophenyl)-4,4,4-trifluorobuta-1,3-dione 0.86 ml of sulfuryl chloride was added to 2.5 g of 1-(4'-chlorophenyl)-4,4,4-trifluorobuta-1,3-dione in 15 ml of trichloromethane. The reaction mixture was stirred for 3 hours and then concentrated under reduced pressure. Yield: 2.8 g; oil. | |
With N-chloro-succinimide Inert atmosphere; Milling; | 1-Aryl-2-chloro-2,4,4,4-tetrafluoro-3,3-dihydroxybutanones; General Procedure General procedure: The corresponding 1-aryl-4,4,4-trifluorobutane-1,3-dione (1.0 equiv) and NCS (1.2 equiv) were triturated together in a mortar under an inert atmosphere. The reaction was monitored by 19F NMR spectroscopy and trituration was continued until full conversion was achieved. The crude reaction mixture was then dissolved in anhyd MeCN and stirred together with Selectfluor (1.5 equiv) at r.t. After full conversion was achieved based on 19F NMR analysis, the solvent was removed and replaced with CH2Cl2. The insoluble Selectfluor was filtered from the reaction mixture and the organic filtrate was washed with H2O. The organic layer was dried (Na2SO4) and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel using with hexanes/EtOAc (90:10) as the mobile phase. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium methylate In methanol; diethyl ether | 6 1-(4'-Chlorophenyl)-4,4,4-trifluorobuta-1,3-dione 1-(4'-Chlorophenyl)-4,4,4-trifluorobuta-1,3-dione At 5° C., 107.8 g of a 30% strength by weight solution of sodium methoxide in methanol were added dropwise to a mixture of 92 g of 4-chloroacetophenone, 800 ml of diethyl ether and 77 g of methyl trifluoroacetate. The reaction mixture was stirred at about 20° C. for 17 hours and the pH was then adjusted to 3 by the addition of 10% strength hydrochloric acid. The organic phase was subsequently separated off, dried over sodium sulfate and finally concentrated under reduced pressure. The crude product was purified by stirring with petroleum ether and filtering off the undissolved fraction. Yield: 105 g; m.p.: 56-57° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With NaCH3COO In methanol byproducts: CH3COOH, NaCl; solns. mixed dropwise at room temp.; filtered, evapd. (vac.), dried (vac., 38°C) for 2 h, crystd. (CH2Cl2/hexane); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | Stage #1: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With phosphorus pentachloride In tetrachloromethane at 30 - 35℃; for 24h; Stage #2: sodium diethylmalonate In ethanol; dichloromethane at -50 - 0℃; for 1h; | |
29% | Stage #1: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With phosphorus pentachloride In tetrachloromethane at 25 - 35℃; for 24h; Stage #2: sodium diethylmalonate In ethanol; dichloromethane at -50 - 0℃; | General procedure for the synthesis of compounds (6a-g) General procedure: A mixture of the corresponding 1-aryl-4,4,4-trifluorobutane-1,3-dione 8 (0.16mol), PCl5 (37.1g, 0.18mol)and CCl4 (10mL) was stirred at 25-35°C for several hours. After complete conversion as indicated by 19F NMR, volatile components were removed under reduced pressure. The residue was diluted with dry CH2Cl2 (100mL), cooled to -50°C and quenched with a cooled to -50°C suspension of sodium diethyl malonate (0.72mol) in absolute ethanol (450mL). After achieving 0°C, the reaction was left under stirring for 1h at this temperature. The dark red reaction mixture was quenched with 10% H2SO4 (1.5L) and the organic layer was washed once with water, distilled under reduced pressure and crystallized from ethanol (cooling to -30°C) to afford pure 6. |
With phosphorus pentachloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With triethylamine In benzene for 74h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tetrachloroplatinate(II) In methanol at 40℃; for 18h; Inert atmosphere; Molecular sieve; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With triethylamine In ethanol at 78℃; for 18h; | 29 EXAMPLE 29[4-(4-Chloro-phenyl)-6-trifluoromethyl-pyrimidin-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine; A mixture of 1-(4-chloro-phenyl)-4,4,4-trifluoro-butane-1,3-dione (50 mg, 0.2 mmol), N-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-guanidine dinitrate (74 mg, 0.2 mmol), and triethylamine (0.14 mL, 1.0 mmol) in ethanol (0.5 mL) was heated to 78° C. for 18 h. The mixture was cooled, diluted with ethyl acetate (30 mL), and then washed with sat. sodium carbonate solution (5 mL) and with brine (5 mL). The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residual material was purified by column chromatography on silica gel (5 g) using ethyl acetate/0-10% ethanol as eluent to give the title compound (10 mg, 11%) as light-yellow solid. Mp 202-204° C.MS ISP (m/e): 460.0 [(M+H)+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile | 69.A Methyl 6-(4-chlorophenyl)-2-(1-methylethyl)-4-(trifluoromethyl)nicotinate EXAMPLE 69A Methyl 6-(4-chlorophenyl)-2-(1-methylethyl)-4-(trifluoromethyl)nicotinate 150 mg (0.599 mmol) of 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione [Katsuyama et al., Synthesis, 1321-1324 (1997)] and 171 mg (1.20 mmol) of methyl 3-amino-4-methylpent-2-enoate [Holz et al., J. Org. Chem. 68., 1701-1707 (2003)] in 2 ml of acetonitrile were reacted at reflux temperature overnight. The volatile components were then removed on a rotary evaporator. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 34 mg (16% of theory) of the target compound. LC-MS (method 6): Rt=1.73 min; MS (ESIpos): m/z=358 [M+H]+. 1H-NMR (400 MHz, DMSO-d6): δ [ppm]=1.31 (d, 6H), 3.11 (sept, 1H), 3.95 (s, 3H), 7.63 (d, 2H), 8.27 (s, 1H), 8.30 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate In benzene for 2h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With triethylamine In toluene at 20 - 80℃; for 1.25h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.6% | With triethylamine In toluene at 20 - 80℃; for 1.25h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 4-chloro-aniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 4-methoxy-aniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 4-nitro-aniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: o-chloroaniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 3,5-Bis-(trifluoromethyl)aniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 4-bromo-aniline With hydrogenchloride; sodium nitrite In water at 20℃; for 2.66667h; Cooling with ice; Stage #2: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With sodium acetate In ethanol; water for 0.75h; Cooling with ice; | 4.1.1. General method for synthesis of 1-(4-chlorophenyl)-2-(2-arylhydrazone)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A cooled sodium nitrite solution (1.5 g in 10 mL of water) was added dropwise during 10 min to an ice-cold solution of the appropriate aniline in concentrated hydrochloric acid (3 mL). The reaction mixture was stirred for 30 min at the same temperature and for 2 h at room temperature to give the corresponding diazonium salt. The solution of diazonium salt was added dropwise with stirring to an ice-cold mixture of trifluoromethyl-1,3-diketone 1 (2.5 g, 0.01 mol) in sodium acetate (4.19 g, 0.05 mol) and ethanol (50 mL) over 15 min. The stirring was continued for 30 min and the solid obtained was collected and crystallized from ethanol to give the corresponding hydrazones 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 52% 2: 24% | In ethanol for 6h; Reflux; regioselective reaction; | 5.2. General procedure for the preparation of 5-hydroxy-5-trifluoromethyl-3-aryl-4,5-dihydropyrazol-1-thiocarboxamides 3c-d and 3-trifluoromethyl-5-arylpyrazol-1-thiocarboxamides 4c-d An ethanolic solution (30 ml) of thiosemicarbazide 1 (0.9 g, 10 mmol) and trifluoromethyl-β-diketones 2c-d (10 mmol) was refluxed for 6 h. The progress of reaction was monitored with the help of TLC. When the reaction was complete, solvent was distilled off under vacuum. The 1H NMR spectra and TLC of reaction mixture showed the presence of two products in the ratio given in refPreviewPlaceHolderTable 1. Column chromatographic separation using silica gel (100-200 mesh) with petroleum ether:ethyl acetate (99:1) afforded 4, further elution of column with petroleum ether:ethyl acetate (97:3) afforded 3. |
With sulfuric acid In ethanol for 6h; Reflux; | 5.3. General procedure for the reaction between thiosemicarbazide 1 and trifluoromethyl-β-diketones 2 in acidic conditions To an ethanolic solution (30 ml) of thiosemicarbazide 1 (0.9 g, 10 mmol) 4-5 drops of H2SO4 were added followed by trifluoromethyl-β-diketones 2c-d (10 mmol) and was refluxed for 6 h. The progress of reaction was monitored with the help of TLC. When the reaction was complete, solvent was distilled off under vacuum. Reaction mixture thus obtained by neutralized by aq. NaOH and was extracted by ethyl acetate (3 × 20 ml). The combined organic extracts were dried over anhyd. sodium sulphate, filtered and concentrated. The 1H NMR spectra and TLC of reaction mixture showed the presence of two products in the ratio given in refPreviewPlaceHolderTable 2. Data of compounds 3 and 4 has already been given above. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: sodium acetylide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione In tetrahydrofuran; 5,5-dimethyl-1,3-cyclohexadiene at -10 - 90℃; for 4h; Inert atmosphere; Stage #2: With sulfuric acid In tetrahydrofuran; 5,5-dimethyl-1,3-cyclohexadiene; hexane; water at 0℃; for 0.5h; Inert atmosphere; regioselective reaction; | 3,6-Bis(trifluoromethyl)-3,6-dihydroxy-1,8-diphenyloct-4-yne-1,8-dione (2a): General procedure: The reaction was conducted under an argon atmosphere. A solution of 4,4,4-trifluoro-1-phenylbutane-1,3-dione (1a) (11.3 g, 52.3 mmol) in dry THF (15 mL) was added gradually to a cooled (-10 °C) mixture of sodium acetylide suspension 18 wt% slurry in xylene (60 mL) and dry THF (50 mL). The mixture was stirred at ambient temperature for 2 h, at 70 °C for 30 min, and at 90 °C for 1.5 h (the low-boiling solvent THF partially distilled off during heating the reaction mixture in the range 70-90 °C). The mixture was cooled to ambient temperature and quenched with cold (0 °C) 10% aqueous H2SO4 (200 mL). Hexane (250 mL) was added, and the resulting mixture stirred at 0 °C for 30 min. The residue was filtered, washed with H2O and hexane, and dried. The dry residue was dissolved in a minimum volume of a hot mixture of hexane-toluene (1:1), the hot solution was passed through a layer of silica gel (5 cm3), and the layer washed with a hot mixture of hexane-toluene (1:1) (20 mL). The resulting residue was filtered, washed with hexane (5 mL) and dried to give compound 2a as a white solid. Yield 8.52 g (71%), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
With sodium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
With sodium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydroxide In ethanol for 2h; Reflux; | 4.2. General method for synthesis of 2-(2-arylidene)-1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione (2a-f) (Scheme 1) General procedure: A mixture of compound 1 (2.50 g, 10 mmol) and the appropriate aldehyde (10 mmol) in ethanolic sodium hydroxide solution (5%, 40 mL) was refluxed for 2 h. The reaction mixture was poured onto ice/cold water and the formed precipitate was filtered off and recrystallized from ethanol to give compounds 2a-f. |
With sodium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With iron(III) chloride In dichloromethane for 3h; Reflux; | 4.4. General method for synthesis of 2-benzyl-1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione (4) (Scheme 1) To a stirred solution of compound 1 (0.25 g, 1 mmol) and benzyl alcohol (0.10 g, 1 mmol) in dry dichloromethane (4 mL) was added anhydrous ferric chloride (0.16 g, 0.1 mmol). The mixture was refluxed for 3 h. The reaction mixture was evaporated under reduced pressure and the residue was crystallized from isopropanol to give compound 4. Yield, 40%; mp 90-91 °C; 1H NMR (CDCl3); δ 7.81-7.40 (m, 9H, Ar-H), 3.8 (t, 1H, CH), δ 3.2 (d, 2H, CH2,J = 7.5 Hz). Anal. Calcd for C17H12ClF3O2: C, 59.93; H, 3.55. Found: C, 60.10; H, 3.83. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With aq. ammonia In water; acetonitrile mixt. of Ag2O, 4,4'-bipy and trifluoroacetonate deriv. stirred in MeCN/H2O; then aq. ammonia poured into mixt.; allowed to evaporate slowly in dark at room temp. for several d; washed with cold MeCN and Et2O; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sulfuric acid In water at 50℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 2-hydrazinobenzothiazole-6-sulfonic acid amide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 3h; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide at 90℃; for 6h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium methylate In methanol; dichloromethane for 4h; Reflux; | |
With sodium methylate In methanol; dichloromethane for 4h; Reflux; | ||
With sodium methylate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In ethanol for 7h; Reflux; | 1 4.2 General procedure for the synthesis of pyrazoles (2a-2i) in ethanol General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-β-diketone 5a-5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20-25°C and the solid thus obtained was filtered to obtain 2a-2i (85-93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30%; 54% | In ethanol; for 7.0h;Reflux; | General procedure: An equimolar mixture of <strong>[23906-13-0]2-hydrazino-4,6-dimethylpyrimidine</strong> 1(0.27 g, 2 mmol) and aryltrifluoromethyl-b-diketones 2d-h (2 mmol) was refluxed in ethanol (25 mL) for 7 h. The reaction wasmonitored by tlc. On completion of the reaction, solvent was evaporated in vacuo. The tlc and 1H NMR of the reaction mixture showed the formation of two products in the ratio given in Table 1. Column chromatography separation using silica gel (100-200 mesh) with petroleum ether : ethyl acetate (99:1) as an eluent afforded 3 and further elution of column with petroleum ether :ethyl acetate (99:2) furnished the second product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With cesium fluoride In acetonitrile for 6h; Reflux; | Reaction of 4,4,4-trifluoro-1-phenylbutan-1,3-dione with triflate 1a in refluxing acetonitrile General procedure: To a solution of 4,4,4-trifluoro-1-phenylbutan-1,3-dione (108 mg, 0.50 mmol) and CsF (228 mg, 1.50 mmol) in acetonitrile (7 mL) was added triflate 1a (253 mg, 0.85 mmol) in acetonitrile (3 mL). After refluxing for 6h, the reaction mixture was washed with water, dried over MgSO4,filtered, and evaporated to give pale yellow oil, which was chromatographed over silica gel by elution with hexane-dichloromethane (1:1) to afford 3-phenylisocoumarin 3b (71.1 mg, 0.32 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Selectfluor In water; acetonitrile at -20℃; for 12h; Inert atmosphere; | ||
With Selectfluor In water; acetonitrile at -20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In acetonitrile for 0.333333h; | 2.2 Preparation of the complexes General procedure: The complexes were synthesized following the same general procedure. For instance, [Cu(BTA)(Phen)NO3] was prepared by the reaction of Cu(NO3)2·3H2O (0.0603981g, 0.25mmol) with 0.25mmol of the organic compound 4,4,4-trifluoro-1-phenyl-1,3-butanedione (HBTA) in acetonitrile (5mL). The mixture was stirred for 20min, followed by the addition of 1,10-phenanthroline (0.25mmol). After some days at room temperature, green crystals were filtered, washed with water and dried under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In acetonitrile for 0.333333h; | 2.2 Preparation of the complexes General procedure: The complexes were synthesized following the same general procedure. For instance, [Cu(BTA)(Phen)NO3] was prepared by the reaction of Cu(NO3)2·3H2O (0.0603981g, 0.25mmol) with 0.25mmol of the organic compound 4,4,4-trifluoro-1-phenyl-1,3-butanedione (HBTA) in acetonitrile (5mL). The mixture was stirred for 20min, followed by the addition of 1,10-phenanthroline (0.25mmol). After some days at room temperature, green crystals were filtered, washed with water and dried under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In methanol at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With Selectfluor In acetonitrile at 90℃; for 3h; Inert atmosphere; Stage #2: With water In acetonitrile for 0.25h; Inert atmosphere; Reflux; Stage #3: With triethylamine In acetonitrile at 20℃; for 16h; Inert atmosphere; regioselective reaction; | |
Stage #1: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With Selectfluor In acetonitrile for 3h; Inert atmosphere; Reflux; Stage #2: With water In acetonitrile for 0.25h; Inert atmosphere; Reflux; Stage #3: With triethylamine In acetonitrile at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With formic acid; C35H47N3O2RuS; triethylamine In chlorobenzene at 60℃; for 20h; Inert atmosphere; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With sodium methylate In methanol for 6h; Reflux; | General Procedure for the Preparation of Title Compounds III General procedure: Compounds III were synthesized according to the method given in [16]. To the solution of sodiummethoxide (0.09 mol of Na + 10 mL of CH3OH), guanidine carbonate (0.08 mol) was added, and themixture was refluxed for 30 min. The appropriate compound II (0.01 mol) was added, then reacted for6 h. Acetic acid was added dropwise to the solution till pH = 4-5 at 0-5 C. The reaction solution wasfiltered, and the filter cake was washed with water (15 mL 2). The crude product was recrystallized from methanol to give pure compound III-1 to III-22. The nuclear magnetic resonance (NMR), infrared(IR), and mass spectrum (MS) data were as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8% | With N-chloro-N-methoxybenzenesulfonamide; potassium carbonate In acetonitrile at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium <i>tert</i>-butylate In neat (no solvent) at 80℃; for 2h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With piperidine In dimethyl sulfoxide at 70℃; | 4.3. Synthesis of 4-[4-aroyl-5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide (8a-8j) General procedure: General procedure: 4-Azidobenzenesulfonamide (4.04 mmol) was dissolved in DMSO (4 mL) in a 50mL round bottom flask.Thereafter, the appropriate aryl 1,3-diketones (4.04 mmol) andorganic base, piperidine (5 mol %) were added to the reactionmixture. After addition, the reaction mixture was stirred at 70 °C insilicon oil bath for 4-6 h and progress of reaction was monitoredthrough thin layer chromatography. After completion, reactionmixture was poured into water after cooling to afford desiredproduct (8a-8j) which was filtered and recrystalized with ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | In isopropyl alcohol at 90℃; | 1 3.1.26. 1-(3-(4-Chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethan-1-one (29) General procedure: A mixture of 2-phenylacetohydrazide (1) (0.10 g, 0.67 mmol) and 1,1,1-trifluoro-5-phenylpentane-2,4-dione (3a) (0.14 g, 0.67 mmol) in a solution of i-PrOH (5 mL) was heated at 90 °C for 48 h. After cooling to room temperature, EtOAc and water were added. The EtOAc extract was washed with water, brine and dried (Na2SO4). Flash chromatography (petroleum ether/EtOAc; 100:0 to 93:7) followed by recrystallization from Et2O/petroleum ether gave 4 (0.17 g, 71%), mp 122-123 °C (Et2O/petroleum ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With sodium hydride In neat (no solvent) for 0.05h; Microwave irradiation; Green chemistry; | Synthesis of 1-[2-(4-chlorophenyl)-1,8-naphthyridin-3-yl]-2,2,2-trifluoroethanone (3d): To a mixture of 2-aminonicotinaldehyde (0.01 mol), active methylene compound like 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione and NaH (0.01 mol) were mixed together without solvent in a 100 mL conical flask covered with a glass funnel and placed in a microwave oven operating at 500 W for 3 min (Table-1). The completion of the reaction was checked by TLC and poured in 50 mL cool water and normal run with dilute hydrochloric acid (dil. HCl). The light yellow solid particle was separated, filtered, dried and recrystallized from acetonitrile afforded. Light yellow solid, m.p. 335-337 °C, yield 74 %. IR (KBr, νmax, cm-1): 3140, 3091 (Ar C-H str), 2996, 2900 (cyclic C-H str), 1672 (C=O str), 1596, 1511 (C=C str), 1462, 1414 (C=N), 1370, 1335 (C-C str), 1281, 1269 (C-N str), 869, 833 (C-F, halogen substituted C str). 1H NMR (DMSO-H2O): δ 9.084-9.104 (1H, d), 8.139 (1H, s), 7.521-7.543 (1H d), 7.260-7.287 (2H, d), 7.087-7.139 (1H, dd), 6.903-7.055 (2H, d). 13C NMR (DMSO-H2O): δ 144.668, 118.778, 122.288, 128.526, 134.808, 136.298, 139.305, 142.037, 145.084, 151.640, 156.397, 164.967 and 169.933. CG-MS: m/z = 336 M+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With triethylamine In methanol at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With triethylamine In 1,4-dioxane; methanol at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 4-[4-(hydrazinocarbonyl)-5-methyl-1H-1,2,3-triazol-1-yl]benzenesulphonamide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 5h; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide at 90℃; | 3 4.2. General procedure for the synthesis of 4-(4-(5-hydroxy-3-aryl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)-5-alkyl/aryl-1H-1,2,3-triazol-1-yl)benzenesulfonamide (9-12) and 4-(5-alkyl/aryl-4-(2-(1,1,1-trifluoro-4-oxo-4-(thiophen-2-yl)butan-2-ylidene)hydrazine-1-carbonyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (13) General procedure: To a solution of Carboxylic acid hydrazides of 1,2,3-triazole bearingbenzenesulfonamide 18 (1.1 mmol) and substituted 1,3-diketones 19(1.1 mmol) in DMF (15 ml), added conc. HCl (1 ml) and then stirred at50 °C for 5 hrs. Thereafter, few drops of conc. H2SO4 were added andthe reaction mixture was further stirred at 90 °C in silicon oil bath for9-12 hrs. The reaction was monitored through TLC and after completion,the reaction mixture was allowed to cool and poured into ice coldwater to obtain a solid which was filtered and dried to afford crudesolid. Crude product thus obtained was recrystallized in appropriatesolvent. It is pertinent to mention here that under the same reactionconditions thienyl substituted 1,3-diketones 19 on reacting withCarboxylic acid hydrazides of 1,2,3-triazole bearing benzenesulfonamide18 afforded corresponding hydrazone-carbonyl-1,2,3-triazoles 13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 4-[4-(hydrazinocarbonyl)-5-phenyl-1H-1,2,3-triazol-1-yl]benzenesulphonamide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 5h; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide at 90℃; | 9 4.2. General procedure for the synthesis of 4-(4-(5-hydroxy-3-aryl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)-5-alkyl/aryl-1H-1,2,3-triazol-1-yl)benzenesulfonamide (9-12) and 4-(5-alkyl/aryl-4-(2-(1,1,1-trifluoro-4-oxo-4-(thiophen-2-yl)butan-2-ylidene)hydrazine-1-carbonyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (13) General procedure: To a solution of Carboxylic acid hydrazides of 1,2,3-triazole bearingbenzenesulfonamide 18 (1.1 mmol) and substituted 1,3-diketones 19(1.1 mmol) in DMF (15 ml), added conc. HCl (1 ml) and then stirred at50 °C for 5 hrs. Thereafter, few drops of conc. H2SO4 were added andthe reaction mixture was further stirred at 90 °C in silicon oil bath for9-12 hrs. The reaction was monitored through TLC and after completion,the reaction mixture was allowed to cool and poured into ice coldwater to obtain a solid which was filtered and dried to afford crudesolid. Crude product thus obtained was recrystallized in appropriatesolvent. It is pertinent to mention here that under the same reactionconditions thienyl substituted 1,3-diketones 19 on reacting withCarboxylic acid hydrazides of 1,2,3-triazole bearing benzenesulfonamide18 afforded corresponding hydrazone-carbonyl-1,2,3-triazoles 13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: 4-[4-(hydrazinocarbonyl)-5-(p-tolyl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 5h; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide at 90℃; | 15 4.2. General procedure for the synthesis of 4-(4-(5-hydroxy-3-aryl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)-5-alkyl/aryl-1H-1,2,3-triazol-1-yl)benzenesulfonamide (9-12) and 4-(5-alkyl/aryl-4-(2-(1,1,1-trifluoro-4-oxo-4-(thiophen-2-yl)butan-2-ylidene)hydrazine-1-carbonyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (13) General procedure: To a solution of Carboxylic acid hydrazides of 1,2,3-triazole bearingbenzenesulfonamide 18 (1.1 mmol) and substituted 1,3-diketones 19(1.1 mmol) in DMF (15 ml), added conc. HCl (1 ml) and then stirred at50 °C for 5 hrs. Thereafter, few drops of conc. H2SO4 were added andthe reaction mixture was further stirred at 90 °C in silicon oil bath for9-12 hrs. The reaction was monitored through TLC and after completion,the reaction mixture was allowed to cool and poured into ice coldwater to obtain a solid which was filtered and dried to afford crudesolid. Crude product thus obtained was recrystallized in appropriatesolvent. It is pertinent to mention here that under the same reactionconditions thienyl substituted 1,3-diketones 19 on reacting withCarboxylic acid hydrazides of 1,2,3-triazole bearing benzenesulfonamide18 afforded corresponding hydrazone-carbonyl-1,2,3-triazoles 13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: 4-[4-(hydrazinocarbonyl)-5-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 5h; Stage #2: With sulfuric acid In water; N,N-dimethyl-formamide at 90℃; | 21 4.2. General procedure for the synthesis of 4-(4-(5-hydroxy-3-aryl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)-5-alkyl/aryl-1H-1,2,3-triazol-1-yl)benzenesulfonamide (9-12) and 4-(5-alkyl/aryl-4-(2-(1,1,1-trifluoro-4-oxo-4-(thiophen-2-yl)butan-2-ylidene)hydrazine-1-carbonyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (13) General procedure: To a solution of Carboxylic acid hydrazides of 1,2,3-triazole bearingbenzenesulfonamide 18 (1.1 mmol) and substituted 1,3-diketones 19(1.1 mmol) in DMF (15 ml), added conc. HCl (1 ml) and then stirred at50 °C for 5 hrs. Thereafter, few drops of conc. H2SO4 were added andthe reaction mixture was further stirred at 90 °C in silicon oil bath for9-12 hrs. The reaction was monitored through TLC and after completion,the reaction mixture was allowed to cool and poured into ice coldwater to obtain a solid which was filtered and dried to afford crudesolid. Crude product thus obtained was recrystallized in appropriatesolvent. It is pertinent to mention here that under the same reactionconditions thienyl substituted 1,3-diketones 19 on reacting withCarboxylic acid hydrazides of 1,2,3-triazole bearing benzenesulfonamide18 afforded corresponding hydrazone-carbonyl-1,2,3-triazoles 13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: ethanol / 18 h / Reflux 2: [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium carbonate / 1,4-dioxane / 20 - 100 °C / Sealed tube; Inert atmosphere; Glovebox | ||
Multi-step reaction with 3 steps 1.1: ethanol / 18 h / Reflux 2.1: potassium acetate; XPhos; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / ethanol / 80 °C 2.2: 20 °C 3.1: potassium <i>tert</i>-butylate; C21H30ClNPPd / tert-Amyl alcohol / 18 h / 65 °C / Sealed tube; Inert atmosphere; Glovebox |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium acetate at 20℃; for 24h; | General procedure for the synthesis of compounds 3-5 General procedure: To a solution of CF3-diketone 2 (1.0 mmol) and NaOAc (0.12 g, 1.5 mmol) in EtOH (5.0 mL) was added nitroalkene 1 (1.0 mmol), and the resulting mixture stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure, washed with H2O (3×3 mL), and the solid that formed was recrystallized from CH2Cl2-hexane (1:2) to give compounds 3a-e or 5a-e as colorless needles. Liquid products 3f-j and 4a were chromatographed on silica gel (eluting with CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium acetate at 20℃; for 24h; | General procedure for the synthesis of compounds 3-5 General procedure: To a solution of CF3-diketone 2 (1.0 mmol) and NaOAc (0.12 g, 1.5 mmol) in EtOH (5.0 mL) was added nitroalkene 1 (1.0 mmol), and the resulting mixture stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure, washed with H2O (3×3 mL), and the solid that formed was recrystallized from CH2Cl2-hexane (1:2) to give compounds 3a-e or 5a-e as colorless needles. Liquid products 3f-j and 4a were chromatographed on silica gel (eluting with CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium acetate at 20℃; for 24h; | General procedure for the synthesis of compounds 3-5 General procedure: To a solution of CF3-diketone 2 (1.0 mmol) and NaOAc (0.12 g, 1.5 mmol) in EtOH (5.0 mL) was added nitroalkene 1 (1.0 mmol), and the resulting mixture stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure, washed with H2O (3×3 mL), and the solid that formed was recrystallized from CH2Cl2-hexane (1:2) to give compounds 3a-e or 5a-e as colorless needles. Liquid products 3f-j and 4a were chromatographed on silica gel (eluting with CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione With iodosylbenzene In dichloromethane at 0 - 5℃; for 0.0025h; Stage #2: benzylamine With Eosin Y; copper(I) bromide In dichloromethane at 20℃; for 3h; Sealed tube; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With Bis(p-nitrophenyl) phosphate; phenylsilane; C28H21P*C19H22NO4PS In toluene at 40℃; for 40h; Inert atmosphere; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With cerium(III) chloride heptahydrate In ethanol at 65℃; for 3h; | General procedure for the synthesis of trifluorotetrahydropyrimidinones/thiones (7a-l) (7i as example): General procedure: 1-(40-Chlorophenyl)-4,4,4-trifluorobutane-1,3-dione (150.0 mg,0.60 mmol), 40-methoxybenzaldehyde (73.0 mL, 0.60 mmol) andurea (108.0 mg, 1.80 mmol) were added to ethanol (2.0 mL), followedby the addition of CeCl37H2O (25 mol%). The reactionmixture was refluxed at 65 C for 3 h. The mixture was allowed tocool to room temperature and poured into crushed ice, stirred for10 min, filtered, washed with cold water and air dried. The solidobtained was recrystallized from hot ethanol to obtain the pureproduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With cerium(III) chloride heptahydrate In ethanol at 65℃; for 3h; | General procedure for the synthesis of trifluorotetrahydropyrimidinones/thiones (7a-l) (7i as example): General procedure: 1-(40-Chlorophenyl)-4,4,4-trifluorobutane-1,3-dione (150.0 mg,0.60 mmol), 40-methoxybenzaldehyde (73.0 mL, 0.60 mmol) andurea (108.0 mg, 1.80 mmol) were added to ethanol (2.0 mL), followedby the addition of CeCl37H2O (25 mol%). The reactionmixture was refluxed at 65 C for 3 h. The mixture was allowed tocool to room temperature and poured into crushed ice, stirred for10 min, filtered, washed with cold water and air dried. The solidobtained was recrystallized from hot ethanol to obtain the pureproduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With cerium(III) chloride heptahydrate In ethanol at 65℃; for 3h; | General procedure for the synthesis of trifluorotetrahydropyrimidinones/thiones (7a-l) (7i as example): General procedure: 1-(40-Chlorophenyl)-4,4,4-trifluorobutane-1,3-dione (150.0 mg,0.60 mmol), 40-methoxybenzaldehyde (73.0 mL, 0.60 mmol) andurea (108.0 mg, 1.80 mmol) were added to ethanol (2.0 mL), followedby the addition of CeCl37H2O (25 mol%). The reactionmixture was refluxed at 65 C for 3 h. The mixture was allowed tocool to room temperature and poured into crushed ice, stirred for10 min, filtered, washed with cold water and air dried. The solidobtained was recrystallized from hot ethanol to obtain the pureproduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With cerium(III) chloride heptahydrate In ethanol at 65℃; for 3h; | General procedure for the synthesis of trifluorotetrahydropyrimidinones/thiones (7a-l) (7i as example): General procedure: 1-(40-Chlorophenyl)-4,4,4-trifluorobutane-1,3-dione (150.0 mg,0.60 mmol), 40-methoxybenzaldehyde (73.0 mL, 0.60 mmol) andurea (108.0 mg, 1.80 mmol) were added to ethanol (2.0 mL), followedby the addition of CeCl37H2O (25 mol%). The reactionmixture was refluxed at 65 C for 3 h. The mixture was allowed tocool to room temperature and poured into crushed ice, stirred for10 min, filtered, washed with cold water and air dried. The solidobtained was recrystallized from hot ethanol to obtain the pureproduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iron(III) trifluoromethanesulfonate In toluene at 100℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: nickel(II) nitrate hexahydrate; 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione In acetonitrile at 20℃; for 0.5h; Stage #2: 1,10-Phenanthroline In acetonitrile for 24h; | 2.2.1. Complex I - [Ni(η2-NO3)(bta)(phen)] General procedure: 0.5 mmol (0.1425 g) of 4,4,4-trifluoro-1-phenyl-1,3-butanedione(Hbta) dissolved in 1 mL of acetonitrile was added to 0.5 mmol(0.1454 g) of Ni(NO3)2·6H2O previously solubilized in 1 mL of acetonitrile.The mixture was kept under magnetic stirring for 30 min atroom temperature. Next, 0.5 mmol (0.0901 g) of 1,10-phenanthroline(phen) dissolved in 1 mL of acetonitrile was added dropwise. After 24 h,a precipitate was isolated by filtration, washed with acetonitrile anddried under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: Selectfluor / acetonitrile; water / 12 h / -20 °C 2.1: C34H37N3O4; potassium dihydrogenphosphate; tetrabutylammonium perchlorate / 1,2-dichloro-ethane / 70 °C / Inert atmosphere; Electrochemical reaction 2.2: 3 h / 70 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: Selectfluor / acetonitrile; water / 12 h / -20 °C 2: tert-butylammonium hexafluorophosphate(V); N-ethyl-N,N-diisopropylamine / 1,2-dichloro-ethane / 3 h / 70 °C / Electrochemical reaction; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid at 50℃; | 4.2.2 Preparation of tert-butyl 7,8-dihydropyrido[4′,3′:3,4]pyrazolo [1,5-a] pyrimidine-9(10H)-carboxylate (3a) General procedure: Propanedial (432mg, 1.2 equiv.) was added to solution 2 (1.19g, 1.0 equiv.) in AcOH (8mL) at room temperature. The mixture was then stirred at 50°C. The reaction was monitored by LC-MS. The mixture was then cooled to room temperature, diluted with water, extracted with ethyl acetate. Combined organic layers were dried over anhydrous Na2SO4, filtered, and evaporated in vacuo. The crude product was purified by silica gel chromatography to get product 3a (534mg, 39%) as a light color solid. | |
With acetic acid at 50℃; | 4.2.2 Preparation of tert-butyl 7,8-dihydropyrido[4′,3′:3,4]pyrazolo [1,5-a] pyrimidine-9(10H)-carboxylate (3a) General procedure: Propanedial (432mg, 1.2 equiv.) was added to solution 2 (1.19g, 1.0 equiv.) in AcOH (8mL) at room temperature. The mixture was then stirred at 50°C. The reaction was monitored by LC-MS. The mixture was then cooled to room temperature, diluted with water, extracted with ethyl acetate. Combined organic layers were dried over anhydrous Na2SO4, filtered, and evaporated in vacuo. The crude product was purified by silica gel chromatography to get product 3a (534mg, 39%) as a light color solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With 1,4-diaza-bicyclo[2.2.2]octane In ethanol for 3h; Reflux; |
Tags: 18931-60-7 synthesis path| 18931-60-7 SDS| 18931-60-7 COA| 18931-60-7 purity| 18931-60-7 application| 18931-60-7 NMR| 18931-60-7 COA| 18931-60-7 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :