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[ CAS No. 169590-42-5 ] {[proInfo.proName]}

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Chemical Structure| 169590-42-5
Chemical Structure| 169590-42-5
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Product Details of [ 169590-42-5 ]

CAS No. :169590-42-5 MDL No. :MFCD00941298
Formula : C17H14F3N3O2S Boiling Point : -
Linear Structure Formula :- InChI Key :RZEKVGVHFLEQIL-UHFFFAOYSA-N
M.W : 381.37 Pubchem ID :2662
Synonyms :
SC-58635
Chemical Name :4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide

Calculated chemistry of [ 169590-42-5 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 26
Num. arom. heavy atoms : 17
Fraction Csp3 : 0.12
Num. rotatable bonds : 4
Num. H-bond acceptors : 7.0
Num. H-bond donors : 1.0
Molar Refractivity : 89.96
TPSA : 86.36 ?2

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.21 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.56
Log Po/w (XLOGP3) : 3.4
Log Po/w (WLOGP) : 5.75
Log Po/w (MLOGP) : 2.65
Log Po/w (SILICOS-IT) : 2.63
Consensus Log Po/w : 3.4

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.57
Solubility : 0.0104 mg/ml ; 0.0000271 mol/l
Class : Moderately soluble
Log S (Ali) : -4.89
Solubility : 0.00488 mg/ml ; 0.0000128 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -6.22
Solubility : 0.000229 mg/ml ; 0.000000601 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.74

Safety of [ 169590-42-5 ]

Signal Word:Danger Class:9
Precautionary Statements:P201-P202-P260-P273-P280-P308+P313-P391-P405-P501 UN#:3077
Hazard Statements:H360-H373-H401-H410 Packing Group:Ⅲ
GHS Pictogram:

Application In Synthesis of [ 169590-42-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 169590-42-5 ]

[ 169590-42-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 720-94-5 ]
  • [ 17852-52-7 ]
  • [ 169590-42-5 ]
YieldReaction ConditionsOperation in experiment
99% at 90℃; General procedure: 4,4,4-Trifluoro-l-(4-methyl-phenyl)-butane-l,3-dione 5 stock solution (7 mL) and (4-Sulfamoylphenyl)hydrazine hydrochloride 6 stock solution (7 mL) were each pumped at a flow rate of 0.125 mL.min 1 into the 2 mL glass mixing chip at room temperature and through the 14 mL PTFE coil heated to 90C. The output of the reactor was collected until no further product was eluted and the solvent removed in vacuo. The solid obtained was suspended in ethyl acetate (30 mL) followed by vacuum filtration. The filtrate was concentrated to obtain a pale yellow solid (0.393 g, 1.0 mmol, 99%). Rf= 0.33 (20% methanol/dichloromethane).
90% In ethanol;Reflux; C01 (23.55 g, 102.3 mmol) was refluxed with 4-sulphonamidophenyl hydrazine HCl (23.95 g, 127.9 mmol) in 700 mL ethanol overnight. The reaction was evaporated, dissolved in 700 mL ethyl acetate, washed with water and brine, dried over magnesium sulfate and evaporated to -100 mL ethyl acetate. The product was crystalized by the addition of ~ 400 mL isooctane. After 15 minutes, the white crystalline solid was broken up, washed with isooctane and dried under vacuum (35.15 g, 90% yield). 1H NMR (400 MHz, CDC13) delta 7.94-7.91 (m, 2H), 7.51-7.49 (m, 2H), 7.21-7.20 (m, 2H), 7.15-7.13 (m, 2H), 6.77 (s, 1H), 2.41 (s, 3H). LC tr=4.27 minutes (C-18 column, 5 to 95% acetonitrile/water over 6 minutes at 1.7 mL/min with detection 254 nm, at 23 C). ES(neg)MS m/z 380 (M-H calcd for C17H14F3N302S requires 380).
80% In ethanol; for 20h;Reflux; A suspension of 2.21 g (9.61 mmol) 3 and 2.36 g (10.57 mmol) 4-hydrazinylbenzensulfonamidehydrochloride, 5, in 25 mL abs. EtOHwas refluxed for 20 h. The resulting solution was concentrated in vaccum. Theresidue was dissolved in 50 mL ethyl acetate, washed with water (2 x 50 mL) andbrine (50 mL). The organic phase was dried over Na2SO4, filtrated andconcentrated in vacuum. The crude product was purified by column chromatographyeluting with n-hexane and ethyl acetate (2:1) to afford 2.91 g (80%) Celecoxib. Modified ADDIN EN.CITEPenning1997111117ThomasD. PenningJohn J.TalleyStephen R.BertenshawJeffery S.CarterPaul W. CollinsStephenDocterMatthew J.GranetoLen F.LeeJames W.MalechaJulie M.MiyashiroRoland S.RogersD. J.RogierStella S. YuGaryD. AndersonEarl G.BurtonJ. NitaCogburnSusan A.GregoryCarol M.KoboldtWilliam E.PerkinsKarenSeibertAmy W. VeenhuizenYanY. ZhangPeter C.IsaksonSynthesisand Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2Inhibitors: Identification of4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide(SC-58635, Celecoxib)J. Med.Chem.J.Med.Chem.1347-13654091997[2] 1H-NMR(250 MHz, CDCl3): delta = 7.89 (d, 2H, J = 8.9 Hz, 2H,6H-Ph),7.46 (d, 2H, J = 8.9 Hz, 3H,5H-Ph), 7.14 (pq, 4H, J1 = 8.0 Hz, J2 = 8.3 Hz, Tolyl), 6.74 (s,1H, Pyr), 5.03 (s, 2H, SO2-NH2),2.37 (s, 3H, -CH3). Mp = 159.6 C, m/z = 382.2 [M+H]+
46% In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4. 14 g, 18. 0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157 -159 C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4. 14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature PC26183 46 and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3. 11 g (8. 2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3. 70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17;H, 3.81; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide. To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamido-phenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159 C.; and a calculated composition of C17H14N3O2SF3; C, 53.54; H, 3.70; N, 11.02. The composition that was found by analysis was: C, 53.17; H, 3.81; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; Step 2: Preparation of 4- [5- (4-methylphenyl)-3- (trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide. [000203] To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8. 2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C
46% In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene CHLORIDE/HEXANE to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 02 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4.14 g, 18.0 MMOL) in 75 mL absolute ethanol, 4.26 g (19.0 MMOL) 4-SULPHONAMIDOPHENYLHYDRAZINE hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was RECRYSTALLIZED from methylene chloride/hexane to give 3.11 g (8.2 MMOL, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 HR4 N3 02 SF3 ; C, 53. 54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
46% In ethanol; for 24h;Heating / reflux; To the digne from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point (mp) of 157-159C ; and a calculated composition of C17 H14 N3 2 SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3.81 ; N, 10.90.
To a 100 mL Morton flask was charged [1G 4-SAPH-HCI] and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 4.5 mL [NAOH] [(1 M] in [H20)] to pH 11.2. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 0.9 with [TRIFLUOROACETIC] acid. At room temperature, 105 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC on a 4.6 mm, 5 micron Supelco [SUPELCOSILE] LC-DP column. HPLC analysis in all of the following examples was done by the same method. Results are given in table 1 a below.
A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
A 50 mL [3-NECK] Morton flask was fitted with a thermometer, a reflux condenser and a nitrogen inlet. To this reactor was charged 25 mL isopropanol and [1G] (4.5 [MMOL)] [4-SAPH-HCI,] followed by the addition of 0.5 g triethylamine (4.4 [MMOL)] to free base the 4-SAPH. The reaction mixture was allowed to stir for 15 minutes at room temperature. To the resultant slurry was added 0.87g (9.2 [MMOL)] chloroacetic acid. The mixture was allowed to stir at room temperature for 15 minutes. After this time period, [1 G] (4.3 [MMOL)] diketone was added and the reaction mixture was heated to 60 [C] and held at this temperature for 2.5 hr. An aliquot was taken and analyzed via HPLC. The reaction was repeated with each of the following acids: acetic, [DICHLOROACETIC,] trichoroacetic, and [TRIFLUOROACETIC.] Comparative results are given in table 2 below.
A 100 mL 3-neck Morton flask was fitted with a reflux condenser, a nitrogen inlet, a thermometer and a glass stopper. This setup was purged with nitrogen for 15 min after which time 1 g (4.47 [MMOL)] [4-SAPH-HCI] and 25 mL anhydrous methyl alcohol was charged to the flask. To the slurry was added 0.5 g (4.95 [MMOL)] triethylamine at room temperature. After 15 minutes, 1 g (8.77 [MMOL)] [TRIFLUOROACETIC] acid was added at room temperature. After 15 minutes at room temperature, the reaction mixture was heated to 55 [C,] 1 g solid diketone (4.3 [MMOL)] was added all at once followed by 5 mL methyl alcohol to wash the addition funnel. Aliquots from the reaction mixture were taken and analyzed by HPLC. Results in mole% by-product formed based on celecoxib at reaction completion are show in table 3 below. The reaction was repeated for the following solvents: Ethyl alcohol, n- Propyl alcohol, i-Propyl alcohol, Trifluoroethanol, and t-Butyl alcohol.
To a 100 mL Morton flask was charged 1.03g 4-SAPH and 20 mL THF. To this slurry, under nitrogen at room temperature, was added 1g NaOMe (25 wt% in [MEOH)] to pH 10.4. The solution turned homogeneous. After 30 minutes the pH of the solution was adjusted to 1.1 with [TRIFLUOROACETIC] acid. At room temperature, 104 mg diketone, in 10 mL THF, was added. Aliquots were taken periodically as the reaction proceeded and analyzed by HPLC. Results are given in table [1B] below.
In ethanol; for 20h;Inert atmosphere; Reflux; General procedure: 4-Hydrazinylbenzenesulfonamide hydrochloride (3?HCl) (982 mg, 4.4 mmol) was added to the stirred solution of diketone 2 (4.0 mmol) in EtOH (60 mL). If free base 3 was used to replace 3?HCl, additional HCl (3 N, 2.0 mL) is needed. The mixture was heated to reflux for 20 h. Then the reaction mixture was concentrated in vacuo. The residue was added EtOAc, washed with water, dried, filtered, and concentrated. The crude product was purified by column chromatography on silica gel (12% MeOH/CH2Cl2) to give a white solid 4 in 85 +/- 5% (n = 3) yield, Rf = 0.78-0.82 (10% MeOH/CH2Cl2).
24.06g With trifluoroacetic acid; In water; isopropyl alcohol; at 55 - 65℃; for 1h; Take another 500 mL three-necked glass vial, add 50 mL of isopropanol, to a solution of hydrazinobenzenesulfonamide hydrochloride (17.4 g, 0.078, 1101) and trifluoroacetic acid (0.428, 0.0037111001), and the temperature was raised to 55 (after adding reaction solution 3, reaction 111, adding50mL water, the temperature rose to 65 C full solution, cooling 10 C per hour, down to 15 C, pumping, 45 C under reduced pressure drying to get celecoxib eight crystal 24.068, the yield of 85% Ie ^: detection purity of 99.7%.
In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.
In ethanol; for 24h;Heating / reflux; To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol, 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride was added. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid, having a melting point of 157-159C ; and a calculated composition of C17Hl4N302SF3 ; C, 53.54 ; H, 3.70 ; N, 11.02. The composition that was found by analysis was: C, 53.17 ; H, 3. 81 ; N, 10.90.

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  • 2
  • [ 720-94-5 ]
  • [ 169590-42-5 ]
YieldReaction ConditionsOperation in experiment
In water; isopropyl alcohol; Step b 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide 1-(4-Methylphenyl)-4,4,4-trifluorobutane-1,3-dione (4.14 g) from step a was stirred in isopropanol (75 ml). 4-sulphonamidophenylhydrazine hydrochloride (4.25 g) was added. The reaction mixture was refluxed under nitrogen atmosphere for 24 hours, cooled to room temperature and filtered, The filtrate was treated with activated carbon at 40-45 C. The product was crystallized by adding water (150 ml). The product was recrystallized from isopropanol and water.
3.11 g (8.2 mmol, 46%) In ethanol; Step 2 Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol was added 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid: mp 157-159 C.; Anal. calc'd for C17 H14 N3 O2 SF3: C, 53.54; H, 3.70; N, 11.02. Found: C, 53.17; H, 3.81; N, 10.90.
3.11 g (8.2 mmol, 46%) In ethanol; Step 2: Preparation of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide To the dione from Step 1 (4.14 g, 18.0 mmol) in 75 mL absolute ethanol was added 4.26 g (19.0 mmol) 4-sulphonamidophenylhydrazine hydrochloride. The reaction was refluxed under argon for 24 hours. After cooling to room temperature and filtering, the reaction mixture was concentrated to afford 6.13 g of an orange solid. The solid was recrystallized from methylene chloride/hexane to give 3.11 g (8.2 mmol, 46%) of the product as a pale yellow solid: mp 157-159 C.; Anal. calc'd for C17 H14 N3 O2 SF3: C, 53.54; H, 3.70; N, 11.02. Found: C, 53.17; H, 3.81; N, 10.90.
In water; ethyl acetate; at 0 - 80℃; for 6h;Product distribution / selectivity; A mixture of 4-Sulphonamidophenylhydrazine hydrochloride (10.5 g), 4,4,4-trifluoro-1-[4-(methyl)phenyl]butane-1,3-dione (10.5 g), ethyl acetate (50 ml) and water (50 ml) was heated at 75-80 C. and stirred for 5 hours. The reaction mixture was cooled to 0-5 C. and stirred for 1 hour. The separated solid was filtered, washed with water (150 ml) and dried (Yield: 27 g).
In methanol; at 65℃; for 10h;Product distribution / selectivity; A mixture of 4-sulphonamidophenylhydrazine hydrochloride (42.2 g), 4,4,4-trifluoro-1-[4-(methyl)phenyl]butane-1,3-dione (40 g) and methanol (860 ml) was heated to 65 C. and stirred for 10 hours. The reaction mixture was cooled to 25-30 C. and the solvent was completely removed under vacuum. The residue was taken in a mixture of ethyl acetate (332 ml) and water (80 ml) and stirred for 10 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×52 ml). The organic layers were combined and washed with water (2×80 ml). The combined organic layer was treated with activated carbon at 60 C. The carbon was removed by filtration and the solvent was distilled off to a volume of about 100-115 ml and n-hexane (320 ml) was added. The reaction mixture was stirred at 30 C. for 30 minutes. The separated solid was filtered and washed with n-hexane (20 ml) (Yield: 55 g, purity 94.3%).

  • 3
  • [ 720-94-5 ]
  • [ 4392-54-5 ]
  • [ 169590-42-5 ]
YieldReaction ConditionsOperation in experiment
Into a 100 mL Morton flask fitted with a reflux condenser, a nitrogen inlet and a thermometer was weighed 67 mg 4-SAPH (free base, 0.36 [MMOL).] To the 4-SAPH was added 15 mL isopropyl alcohol followed by 5 mL of a 0.36M TFA stock solution (in isopropyl alcohol). The mixture was heated to [40C] with an oil bath giving a homogeneous solution. At [40C] a 10 ml aliquot of a 0.036M 1,1, 1- [TRIFLUORO-4- (4APOS;-METHYLPHENYL)-2,] 4-butanedione (in isopropyl alcohol) diketone stock solution, preheated to [40C,] was added all at once to the 4-SAPH mixture. Aliquots were taken periodically [(200] [UL),] quenched in 0.2M [NAOH] (in 55: 45 acetonitrile : water), and cooled in ice. Analysis was carried out by HPLC and area percent values were converted to molar concentrations using standards. The results using four different concentrations of 4-SAPH are given in table 4 below for the initial rate of [CELECOXIB] and Hydroxyregioisomer formation. The diketone concentration for all four trials was 12 mmolar.
With hydrogenchloride; In water; at 98 - 100℃; Stage-2:Preparation of 4-[5-(4-methylphenyl)-3-(trifluorornethyl)-lh-pyrazol-l- yljbenzenesulfonamide (Celecoxib) (I) l-(4-Methylphenyl)-4,4,4-trifluorobutane-l,3-dione (IV) (80 g, 0.348 mol), 4- hydrazinophenylsulfonamide (V) (77.74 g, 0.348 mol) and concentrated hydrochloric acid (18.6 g) were added to DM water (500 ml) and heated to 98-1000C. The mass was stirred for 4 hr to complete the reaction. The reaction mass was cooled to 70-75 C and a mixture of toluene (600 ml) and methanol (10 ml) was added to the reaction mass. After 1 hr stirring at 70-750C, the reaction mass was cooled to 20-250C, the product was filtered and lambdavashed with toluene (100 ml) followed by DM water (200 ml). The product obtained was dried at 55-600C under reduced pressure to produce 1 15 g of Celecoxib crude. Chromatographic purity: 99percent(by PTPLC, by area normalization)
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