Structure of 5932-27-4
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 5932-27-4 |
Formula : | C6H8N2O2 |
M.W : | 140.14 |
SMILES Code : | O=C(C1=NNC=C1)OCC |
MDL No. : | MFCD00159643 |
InChI Key : | MSPOSRHJXMILNK-UHFFFAOYSA-N |
Pubchem ID : | 7147518 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 34.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.98 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.07 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.77 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.02 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.37 |
Solubility | 6.03 mg/ml ; 0.0431 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.5 |
Solubility | 4.38 mg/ml ; 0.0313 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.69 |
Solubility | 2.87 mg/ml ; 0.0205 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.61 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.72 |
* 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 |
---|---|---|
96% | With sulfuric acid; at 80℃; for 2h; | To solution of ethanol (50 mL) and 3-pyrazolecarboxylicacid (1.112 g 10 mmol) at 80 °C was added concentratedsulfuric acid (2 mL), and after 2 h of stirring theethyl 1H-pyrazole-3-carboxylate was obtained (1.350 g,9.6 mmol, 96 percent). |
93% | With sulfuric acid; at 100℃; for 4h;Inert atmosphere; | Ethyl 1H-pyrazole-3-carboxylate (6) A 100 mL Schlenk tube was dried under vacuum, filled with nitrogen and charged with 0.5 g (4.461 mmol, 1.0 eq) 1H-pyrazol-3-carboxylic acid which was dissolved in 20 mL EtOH. After adding 1.31 g (0.72 mL, 13.382 mmol, 3.0 eq) conc. H2SO4 the colorless reaction mixture was heated to reflux (100° C.) and stirred at this temperature for 4 h. TLC analysis (DCM/MeOH 95:5) indicated full conversion of the starting material. After cooling to rt the mixture was transferred to a flask to remove the solvent at a rotary evaporator. The colorless residue was diluted in 20 mL water and neutralized with 17 mL saturated aqueous NaHCO3 solution. Thereby a white solid precipitated. The aqueous layer was extracted with EtOAc (4*50 mL), dried over MgSO4 and the solvent was evaporated under reduced pressure to yield the pure title compound. yield: 582.5 mg (93percent); colorless solid; M.p.: 158-161° C.; Rf (DCM/MeOH 95:5): 0.42; 1H-NMR (300 MHz, CDCl3): delta (ppm)=10.69 (bs, 1H, NH), 7.84 (d, 4J=2.1 Hz, 1H, Ar-H), 6.86 (d, 4J=2.1 Hz, 1H, Ar-H), 4.43 (q, 3J=7.2 Hz, 2H, CH2), 1.41 (t, 3J=7.2 Hz, 3H, CH3); 13C-NMR (75.5 MHz, CDCl3): delta (ppm)=161.8 (C=O), 141.6 (Cq), 132.3 (CHAr), 107.8 (CHAr), 61.1 (CH2), 14.3 (CH3); GC-MS (NM-50_S2): tR=4.655 min (m/z=140.1, 98.0percent M+, BP: 95.0). |
92% | With sulfuric acid;Reflux; | 1H-pyrazol-3-formic acid (7.25 g, 64.7 mmol) was dissolved in absolute ethanol (100 mL), and concentrated sulfuric acid (0.7 mL) was added. The reaction liquid was heated and refluxed overnight. The reaction liquid was concentrated in vacuo, and the residue was diluted with ethyl acetate, washed with saturated sodium bicarbonate, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give ethyl 1H-pyrazol-3-formate (8.35g, 92percent yield), as a off-white solid. 1H NMR (400MHz, CDCl3) delta 12.4 (brs, 1H), 7.74 (d, J = 2.4 Hz, 1H), 6.86 (d, J = 2.4 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H). |
80% | With sulfuric acid;Heating / reflux; | 1 H-Pyrazole-3-carboxylic acid (2.0 g, 17.84 mmol) was dissolved in ethanol (20 ml_), sulfonic acid (1 ml_) was added and the reaction mixture was heated to reflux overnight. Evaporation in vacuo followed by addition of water and aqueous sodium carbonate gave a white precipitate. Filtration followed by wash with water gave 1 H- pyrazole-3-carboxylic acid ethyl ester (2.0 g, 80percent) as white crystals. |
72% | With sulfuric acid; for 24h;Reflux; | General procedure: To a suspension of 4-methoxy-3,5-dimethylbenzoic acid (4 g, 22.2 mmol) in MeOH (60 mL) sulphuric acid was added (1 mL) and mixture stirred at reflux for 1 day. Water was added and it was extracted with AcOEt, organic layers were put together and dried over sodium sulphate and concentrated. The oil thus obtained was purified by normal phase chromatography with 5percent MeOH/DCM to yield the title compound as a colorless oil (99percent yield). LRMS: m/z 195 (M+1)+ Retention time: 6.17 min (Method B) 1H NMR (250 MHz, DMSO-d6) delta ppm 2.30 (s, 6 H) 3.74 (s, 3 H) 3.87 (s, 3 H) 7.71 (s,2H).; Obtained (72percent) from 1H-pyrazole-3-carboxylic acid following the procedure described in Preparation 117, using ethanol as solvent. LRMS: m/z 139 (M-1)+ Retention time: 2.13 min (Method A) |
72% | With sulfuric acid; for 12h;Reflux; | Example 14A1 lH-Pyrazole-3-carboxylic acid ethyl ester To a solution of lH-pyrazole-3-carboxylic acid (2.0 g, 17.8 mmol) in anhydrous ethanol (20 mL) was added concentrated H2SO4 (1 mL) at room temperature. The mixture was refluxed for 12 hours. TLC (neat EtOAc) indicated that the reaction was completed. The mixture was concentrated, the residue was washed with aqueous NaHC03 (20 mL), extracted with dichloromethane (50 mL x 3). The organic layer was dried over Na2S04, filtered, and concentrated in vacuum to give Example 14A1 (1.8 g, yield 72percent) as a white solid. |
Description 1; Ethyl 1H-pyrazole-3-carboxylate (D1); 1 H-pyrazole-3-carboxylic acid (1.Og, 8.9 mmol), was dissolved in ethanol (~12ml) and sulphuric acid added (1.5ml). the solution was heated at reflux overnight. The reaction mixture was concentrated in vacuo and water (-2OmI) added, the solution was neutralised with sodium bicarbonate. Ethylacetate (~70ml) was added and the layers partitioned, the aq was extracted with ethylacetate (~70ml) and the combined organics were dried (MgSO4) and concentrated in vacuo to yield the title compound as a white solid (1.21g, 8.64 mmol). deltaH (CDCI3, 400 MHz): 7.77 (1 H, d), 6.86 (1 H, d),4.43 (2H, quart), 1.42 (3H, t). | ||
With sulfuric acid; for 20h;Heating / reflux; | 1 - ( [2-(trimethylsilyl)ethoxy]methyl) - lH-pyrazole-3 -carbaldehyde was prepared as follows: 3-Methyl pyrazole (50 g, 0.61 mol) was placed in a 5 L round-bottom flask equipped with mechanical stirrer. 3 L of water was added and heated to 80 C. KMn04 (211.90 g, 1.34 mol) was added portion wise and refluxed for 4.5 h. After stirring at rt overnight, solid was filtered and washed with water. The water was removed in vacuo and 100 mL of water was kept in the flask which was acidified with 1 N HCl to pH 4. It was extracted with EtOAc (2x 1L), washed with brine (2x150 mL), dried over MgS04, filtered and removed in vacuo to yield 1H-pyrazole-3-carboxylic acid (38 g, 56percent) as a white solid. 38 g (0.34 mol) of IH-pyrazole-3-carboxylic acid was refluxed in anhydrous ethanol (1 L) and conc. sulfuric acid (60 mL) for 20 h under nitrogen. Ethanol was removed and crude was basified to pH 8. Precipitated solid was filtered. The filtrate was extracted with THF/CHC13 (2: 3, 3x 1 L), dried over MgS04, filtered and removed in vacuo to yield ethyl 1H-pyrazole-3- carboxylate (39 g, 82percent) as a white solid. To a suspension of ethyl 1H-pyrazole-3-carboxylate (4.42 g, 31.57 mmol) in 1,4-dioxane (140 mL) under N2 atmosphere at 0 C was added NaH (0.91 g, 37.88 mmol) and stirred for 15 min. Neat SEM-Cl (5.79 g, 34.73 mmol) was added drop wise to reaction mixture and stirred overnight at rt. It was quenched with water (30 mL) and excess 1,4-dioxane was removed in vacuo. The residue was extracted with EtOAc (2x250 mL), washed with water (1x50 mL), dried over MgS04, filtered and removed in vacuo to give crude ethyl 1 - [2- (trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carboxylate (8.84 g) as a yellow oil. The crude material was used in next step without purification. To a suspension of LiAlH4 in THF (100 mL) at 0 C under N2 atmosphere was added a solution of ethyl 1- f [2-(trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carboxylate (8.88 g, 32.88 mmol) slowly. After addition was completed the cooling bath was removed and reaction mixture was stirred overnight. It was quenched with water (10 mL) carefully at 0 C. THF was removed and residue was diluted with DCM (250 mL) and organic layer was separated, dried over MgS04 and removed in vacuo. The crude material was plugged thru a pad of silica gel with EtOAc/hexanes (from 10percent to 100percent) to yield (1-[2- (trimethylsilyl)ethoxy]methyl) -lH-pyrazol-3-yl)methanol (5.80 g, 77percent) as an yellow oil. 53.75 g (0.24 mol) of (1- f [2-(trirnethylsilyl)ethoxy]methyl}-1H pyrazol-3-yl)methanol was dissolved in THF and 122.97 g (1.41 mol) of Mn02 was added. The resulting mixture was refluxed for 60 h. Solid material was filtered through a pad of celite and washed with hot THF. The filtrate was removed in vacuo to give crude product. The crude was plugged thru a pad of silica gel and eluted with EtOAc/hexanes (from 20percent to 50percent) to yield 1-[2- (trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carbaldehyde (50.88 g, 86.5percent) as a red oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(a) 4-Fluoro<strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong>The sub-title compound was prepared from <strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong> in accordance with a literature procedure (R. Storer, et ah, Nucleosides Nucleotides 18, 203 (1999). A mixture (-2:1) of sub-title compound and unreacted starting material was obtained and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of ethyl-3-pyrazole carboxylate (3.53 g, 25.2 mmol) in DMF (40 mL) at 0° C. was added sodium hydride (60percent, 1.21 g, 30.2 mmol). The resulting mixture was stirred at room temperature for 40 min followed by the addition of 5-nitro-2-bromopyridine (5.1 g, 25.2 mmol). After being stirred for 20 min, the reaction mixture was partitioned between dichloromethane (1000 mL) and water (500 mL), the organic phase was washed with water (3.x.500 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography using 80percent DCM/hexane to give the desired product. To this nitro intermediate (6.77 g, 25.8 mmol) in acetic acid (220 mL) was added zinc powder (16.77 g, 258 mmol). The resulting mixture was heated at 60° C. for 30 min before it was filtered. The filtrate was concentrated in vacuum. To the residue was added DCM (1000 mL) and saturated sodium bicarbonate (1000 mL), and the resulting mixture was stirred at room temperature overnight. The organic phase was then washed with saturated sodium bicarbonate, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography using 5percent methanol in DCM (containing 0.1percent triethylamine) to give the desired product as a yellow solid. To this amine intermediate (5.96 g, 25.7 mmol) in tetrafluoroboric acid (48percent, 130 mL) at 0° C. was added a solution of sodium nitrite (1.95 g, 28.3 mmol) in water (20 mL) dropwise. The resulting solution was stirred at 0° C. for 1 h before filtration. The solid was washed with water and diethyl ether to give the desired product as a yellow solid. A mixture of this diazo intermediate (6.66 g) in acetic anhydride (250 mL) was heated at 70° C. overnight before it was concentrated in vacuo. The residue was purified by flash chromatography eluting with DCM to give the desired product as a white solid. A solution of this acetate intermediate (3.5 g, 12.7 mmol) in ethanol (400 mL) in the presence of 4 drops of sulfuric acid was heated under reflux overnight. After being concentrated in vacuo, the residue was partitioned between DCM (300 mL) and water (200 mL). The pH of the resulting mixture was adjusted to pH=5 by saturated sodium bicarbonate solution. The DCM phase was dried with sodium sulfate and concentrated in vacuo to give the product as a solid. To a solution of this hydroxyl intermediate (2.86 g, 12.3 mmol) in DMF (40 mL) at 0° C. was added sodium hydride (60percent, 589 mg, 14.73 mmol). The resulting mixture was stirred at room temperature for 40 min followed by adding 4-methoxybenzyl alcohol (2.31 g, 14.73 mmol) and sodium iodide (10 mg). The resulting mixture was heated at 80° C. for 0.5 h. After being cooled to room temperature, the reaction mixture was partitioned between DCM (500 mL) and brine (500 mL). The DCM phase was washed with brine (3.x.500 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was treated with 20percent EtOAc/hexane (50 mL) and the mixture was filtered to give the desired product. The filtrate was concentrated and the resulting residue was purified by flash chromatography using 20percent EtOAc/hexane to give additional product as a white solid. A suspension of this ethyl ester intermediate (4.13 g, 11.9 mmol) and lithium borohydride (384 mg, 17.6 mmol) in THF (300 mL) was heated under reflux overnight before it was cooled to 0° C. and quenched by 1N HCl until pH=6. The resulting mixture was diluted in EtOAc (400 mL) and washed with saturated sodium bicarbonate (2.x.400 mL), dried over sodium sulfate and concentrated in vacuo to give the desired product as a white solid. To a solution of this alcohol (3.7 g, 11.88 mmol) in DCM (200 mL) at 0° C. was added pyridine (1.13 g, 14.27 mmol), triphenylphosphine (8.73 g, 33.29 mmol) and NBS (6.34 g, 35.66 mmol). The resulting solution was stirred at 0° C. for 1.5 h. The DCM phase was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography eluting with DCM to give the product as a white solid. To a solution of dimethylmalonate (6.0 g, 45.6 mmol) in DMF (100 mL) at 0° C. was added sodium hydride (2.0 g, 50.15 mmol, 60percent). The mixture was stirred at 0° C. for 40 min before addition of the bromide intermediate (3.41 g, 9.12 mmol) as one portion. The resulting mixture was stirred at room temperature for 40 min before it was partitioned between ethyl acetate (500 mL) and saturated ammonium chloride (300 mL). The EtOAc phase was washed with brine (3.x.500 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography eluting with 20percent EtOAc/hexane to give the product as a white solid. To a solution of this diester (3.8 g, 8.9 mmol) in a mixture solvents of THF/MeOH/H2O (3:1:1, 300 mL) was added lithium hydroxide (1N, 150 mL) dropwise at room temperature. The solution was stirred for 40 min before it was concentrated in vacuo to remove ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; | <strong>[5932-27-4]1H-<strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong></strong> (13.0g, 93 mmol) was dissolved in dimethylformamide (200ml). Potassium carbonate (32g, 232 mmol) was added to the solution, followed by 4-chloro-2- (bromomethyl) phenyl phenylmethyl ether (29g, 93 mmol) and the reaction mixture stirred overnight at room temperature under argon. Water and ethyl acetate were added and the layers separated. The aqueous phase was re-extracted with ethyl acetate. The organic phases were combined and washed with water followed by brine. The extracts were dried (Na2SO4) and evaporated. The residue was purified by on a biotage (15-25percent ethyl acetate: hexane) to yield the title compounds. 1- ( {5-chloro-2- [ (phenylmethyl) oxy] phenyl} methyl)-<strong>[5932-27-4]1H-<strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong></strong>: (13. 90g, 40percent). t = 3.40, no ion observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; lithium iodide; In 1-methyl-pyrrolidin-2-one; at 80℃; for 24h; | Preparation 18 2-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazole-3-carboxylic acid ETHVL ester Ethyl-pyrazole-3-carboxylate (980mg, 7. 0MMOL), 2- (2-bromoethoxy)-tetrahydro- 2H-pyran (1.57g, 7. 5MMOL), potassium carbonate (1. 01G, 7. 3MMOL) and lithium iodide (46. 8mg, 0. 35MMOL) were dissolved in 1-METHYL-2-PYRROLIDINONE (1 OML) and the reaction mixture heated to 80°C for 24 hours. The reaction mixture was allowed to cool for 17 hours and then diluted with a mixture of ethyl acetate: water 1: 1 (500mL). The organic layer was washed with water (3X250ML), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with cyclohexane : ethyl acetate 90: 10 to 80 : 20 to 75: 25 to 50: 50. The appropriate fractions were combined and concentrated in vacuo to yield the title product. HNMR (CDCI3, 400MHZ) : 1.40 (t, 3H), 1.42-1. 80 (m, 6H), 3.43 (m, 1H), 3.60 (m, 1H), 3. 78 (m, 1H), 4.04 (m, 1H), 4.35 (q, 2H), 4.55 (m, 1H), 4.82 (m, 2H), 6.81 (m, 1 H), 7. 48 (m, 1 H). MS ES+ m/z 291 [MNa] + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(b) 4-Fluoropyrazole-3-carboxylic acidSodium hydroxide (aq., 2M, 18 mmol; 9 mL) was added to a solution of a mixture (-2:1) of 4-fluoro<strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong> and <strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong> (1.2 g, ~8 mmol; see step (a) above) in dioxane (9 mL) at rt and was stirred for 16 h. A second portion of aqueous sodium hydroxide (2M, 18 mmol, 9 mL) was added and the mixture was stirred for another 4 h. The mixture was acidified with HCl (aq., 2M, 20 mL), concentrated, stirred with MeOH (30 mL) and filtered. The filtrate was concentrated and the residue crystallised from HCl (aq., 0.01M)<to give a mixture (-3:1) of the sub-title compound and pyrazole- 3-carboxylic acid as a white solid (Yield: 267 mg (-2 mmol, ~25percent)). This mixture was employed without further purification.1H-NMR (DMSO-d6): delta 13.7-13.1 (br s, 1.3H), 7.9-7.7 (m, IH), 7.73 (d, 0.3H), 6.70 (d, 0.3H). | ||
With sodium hydroxide; water; In 1,4-dioxane; at 20℃; for 20h; | 4-Fluoropyrazole-3-carboxylic acid Aqueous NaOH (2M, 18 mmol, 9 mL) was added to a solution of a mixture (~2:1) of 4-fluoro<strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong> and <strong>[5932-27-4]pyrazole-3-carboxylic acid ethyl ester</strong> (1.2 g, ~8 mmol; see step (a) above) in dioxane (9 mL) at room temperature and was stirred for 16 h. A second portion of aqueous NaOH (2M5 18 mmol, 9 mL) was added and the mixture was stirred for another 4 h. The mixture was acidified with aqueous HCl (2M, 20 mL), concentrated, stirred with MeOH (30 mL) and filtered. The filtrate was concentrated and the residue was crystallised with aqueous HCl (0.0 IM) to give a mixture (-3:1) of the sub-title compound and pyrazole-3-carboxylic acid as a white solid (Yield: 267 mg (~2 mmol, -25percent)). This mixture was employed without further purification. 1H-NMR (DMSO-d6): delta 13.7-13.1 (br s, 1.3H), 7.9-7.7 (m, IH), 7.73 (d, 0.3H), 6.70 (d, 0.3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;copper(I) oxide; (E)-2-hydroxylbenzaldehyde oxime; In acetonitrile; at 82℃; for 16h; | EXAMPLE 19; The fluoro bromopyridine (1 eq, Ig), pyrazole (4 eq, 5.023 g), ligand (0.2 eq, 0.196 g), Cu2O (0.05 eq, 51 mg) and Cs2CO3 (2 eq, 4.65 g) were mixed in CH3CN (8 mL) and heated to 82 0C in a sealed vessel for 16 h under N2. The solution was diluted with DCM and filtered through Celite, partitioned with water, and then brine. The product was evaporated in vacuo, and purified by column chromatography (SiO2) with 10 to 20percent EtOAc/hexanes to obtain the major regioisomeric product as a white solid. Then LiBELi (2 eq, 128 mg) was added to this ester intermediate (1 eq, 690 mg) in THF (30 mL) and heated to reflux for 15 h. Then 0.1 N HCl (a few drops) was added and stirred for 1 h, followed by a DCM/H2O partition, and the aqueous layer was basified with NaOH to pH = 9 and extracted with DCM. The combined organic phase was dried to obtain the alcohol as a white solid. Iodine (1.52 eq, l.O58g) in AcOEt (25 ml) was added to an AcOEt (25 mL ) solution of this alcohol (1 eq, 530 mg), followed by Ph3P (1.52 eq, 1.094 g) and imidazole (1.52eq, 0.284 g) over 10 min at RT. The solution was stirred for 1 h and washed with Na2S2O3 and brine. The product was dried in vacuo, and the solid residue was extracted with Hexanes 3 x 70 ml and filtered. The filtration was dried to obtain the iodide product as a white solid. Then KOtBu ( 1.5 eq, 250 mg) was added to N-(diphenylmethylene)- glycine ethyl ester (1.5 eq, 595 mg) in THF at RT and stirred for 10 min. To this solution was added the iodide intermediate (1 eq, 450 mg) in THF (5 mL) at -78 0C, and the mixture was slowly warmed to RT over 2 h. An additional 1 eq of KOtBu was added to the solution at RT and stirred for 50 h at RT. The mixture was quenched with NH4Cl and extracted with DCM, washed with H2O and then brine, and dried in vacuo. The residue was purified by column chromatography (hex/AcOEt - 20percent) to obtain the product. This intermediate (1 eq. 200 mg) was dissolved in saturated 7 N NH3/MeOH (7 mL) solution and heated to 60 0C for 24 h in a sealed tube. The reaction mixture was dried in vacuo and, the residue was dissolved in 5 ml THF and 1 N HCl (2 mL) at RT and heated to 60 0C for 20 min. The THF was removed in vacuo. The aqueous layer was washed with Et2O, dried in vacuo to obtain the amino carboxamide as a white solid HCl-salt. The amide intermediate (1 eq, 68 mg), triflate (1.2 eq, 82 mg), Pd2(DBA)3 (0.1 eq. ), Xantphos (0.2 eq, ) and Cs2CO3 (2.4 eq, 186 mg) were combined in dioxane (2 mL) under N2 and heated to 75 0C for 13 h. The mixture was cooled and diluted with CH2C12 (2 mL), filtered through Celite, and the CH2CI2 removed in vacuo, and Et2psi was added to the filtrate and extracted with 3 N HCl (3 x 10 mL). The combined aqueous layer was basified with Na2CO3 to pH== 9 at 0 0C and extracted with AcOEt (3 xlO mL). The combined organic layer was dried in vacuo to obtain the crude product as a light yellow oil. Lastly, LiOH (0.5 M, 3 mL) was added to this ester in THF/MeOH at 0 0C <n="51"/>and stirred for 20 h. Then AcOH was added to acidify to pH= 7 at 0 0C and HPLC purification provided the product. 1HNMR, CD3OD delta 8.48 (d, IH), 8.30 (d, IH), 7.99(dd, IH), 7.74 (m, IH), 6.43(d, IH), 4.37 (t, IH), 3.50(d, 2H), 2.88 (m, 2H), 2.29 (br, 2H), 1.62 (m, 4H); LCMS m/z 374 (M+H). | |
29 g | With copper(l) iodide; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 90℃; for 7h; | Reference Example 27: Ethyl-1-(5-fluoropyridin-2-yl)-1H-pyrazol-3-carboxylate To a solution of <strong>[5932-27-4]ethyl-1H-pyrazole-3-carboxylate</strong> (25.0 g, 178.4 mmol) and 2-bromo-5-fluoropyridine (47.1 g, 267.6 mmol) in DMF (300 mL), copper(I) iodide (8.5 g, 44.6 mmol), rac-trans-N,N'-dimethylcyclohexane-1,2-diamine (28.1 mL, 178.4 mmol) and Cs2CO3 (116.2 g, 356.8 mmol) were added, and the resulting mixture was stirred for 7 hours at 90°C. The reaction mixture was allowed to cool to room temperature, then water and EtOAc were added thereto, followed by filtration through Celite®. The organic layer was taken out from the filtrate, washed with a saturated aqueous solution of sodium chloride, dried over Na2SO4, then the drying agent was filtered off, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (HP-Sil 50 g, hexane/EtOAc = 70/30 to 0/100). The obtained solid was stirred and washed in hexane/EtOAc = 4/1 and filtered out to obtain the title compound (29.0 g) (colorless solid). MS (ESI pos.) m/z: 236 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; In N,N-dimethyl-formamide; for 0.866667h; | Description 11: 1-tert-Butoxvcarbonvlmethvl-1 H-pvrazole-4-carboxylic acid ethyl ester Potassium tert butoxide (0.045g) was added, in portions, to a stirred solution of 3- (ethoxycarbonyl) pyrazole [CAS 37622-90-5] (0.050g) in N, N- dimethylformamide (0. 5mol). The mixture was stirred for 5 min then tert- butylbromoacetate (0.078g) was added, in portions over 2 min. The mixture was stirred for 0.75h then partitioned between ethyl acetate (30moi) and 1. 0M aqueous sodium bicarbonate (20ml). The organic phase was separated, washed with water (2x20m1), dried (Na2SO4) and concentrated in vacuo to give the title compound (0.073g) as a colourless, viscous oil. LC-MS: Rt = 2.78min. Mass Spectrum m/z 255 [MH+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; In ethanol; at 60℃; for 3h; | Description 36; Ethyl 1 -[(3-chloro-4-cyanophenyl)methyl]-1 H-pyrazole-3-carboxylate (D36); A suspension of ethyl 1 H-pyrazole-3-carboxylate (D1 ) (280mg, 2.0 mmol), 4- (bromomethyl)-2-chlorobenzonitrile [WO 2007/039177] (460mg, 2 mmol) and potassium t-butoxide (246mg, 2.2 mmol), in ethanol (15ml) was heated at 6O0C for 3 hours. The reaction mixture was concentrated in vacuo and dissolved in water (~25ml) and ethylacetate (~25ml), the layers were partitioned and the aq was washed twice with ethylacetate (2x 15ml). The combined organics were passed through a phase separating cartridge to dry and concentrated in vacuo. The crude product was purified by Biotage SP4 with 25S cartridge and 10-70percent ethylacetate/hexane as eluant. The product containing fractions were combined to generate two products, one of which was the title compound as a white solid (21 1 mg, 0.73 mmol). MS (ES+): requires C14H1235CIN3O2 289; found 290 (M+H+). |
Tags: 5932-27-4 synthesis path| 5932-27-4 SDS| 5932-27-4 COA| 5932-27-4 purity| 5932-27-4 application| 5932-27-4 NMR| 5932-27-4 COA| 5932-27-4 structure
A242849 [15366-34-4]
Methyl 1H-pyrazole-3-carboxylate
Similarity: 0.96
A105679 [88529-79-7]
Ethyl 1-methyl-1H-pyrazole-3-carboxylate
Similarity: 0.92
A107942 [105434-90-0]
Ethyl 5-amino-1H-pyrazole-3-carboxylate
Similarity: 0.92
A146155 [632365-54-9]
Methyl 5-amino-1H-pyrazole-3-carboxylate
Similarity: 0.90
A569835 [6076-12-6]
Ethyl 4-methyl-1H-pyrazole-3-carboxylate
Similarity: 0.89
A242849 [15366-34-4]
Methyl 1H-pyrazole-3-carboxylate
Similarity: 0.96
A105679 [88529-79-7]
Ethyl 1-methyl-1H-pyrazole-3-carboxylate
Similarity: 0.92
A107942 [105434-90-0]
Ethyl 5-amino-1H-pyrazole-3-carboxylate
Similarity: 0.92
A146155 [632365-54-9]
Methyl 5-amino-1H-pyrazole-3-carboxylate
Similarity: 0.90
A569835 [6076-12-6]
Ethyl 4-methyl-1H-pyrazole-3-carboxylate
Similarity: 0.89
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 :
Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL