Structure of 874219-45-1
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CAS No. : | 874219-45-1 |
Formula : | C8H8BClO4 |
M.W : | 214.41 |
SMILES Code : | ClC1=C(C=C(C=C1)B(O)O)C(=O)OC |
MDL No. : | MFCD06801690 |
InChI Key : | YEPWHDGFBVDINZ-UHFFFAOYSA-N |
Pubchem ID : | 23005334 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.56 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.76 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.2 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.11 |
Solubility | 1.65 mg/ml ; 0.0077 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 1.04 mg/ml ; 0.00487 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.99 |
Solubility | 2.2 mg/ml ; 0.0103 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 |
-6.68 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 |
0.0 |
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 |
1.0 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) |
1.99 |
* 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 |
---|---|---|
61.0% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 100.0℃; for 6.0h;Microwave irradiation; | Intermediate 112 : methyl 2-chloro-5-(3-nitropyridin-2-yl)benzoate; 2-Bromo-3-nitropyridine (1.25 g, 6.16 mmol), 4-chloro-3- (methoxycarbonyl)phenylboronic acid (1.32 g, 6.16 mmol), tetrakis(triphenylphosphine)palladium(0) (0.36 g, 0.310 mmol) and sodium carbonate (0.653 g, 6.16 mmol) were suspended in toluene (15 mL) and ethanol (15.0 mL) and sealed into a microwave tube. The reaction was heated to 100 0C for 5 hours in the microwave reactor and cooled to RT. The reaction was incomplete and further 2-bromo-3- nitropyridine (0.625 g, 3.08 mmol) was added and the mixture was heated to 100 0C for a further 1 hour. The reaction mixture was filtered through celite, rinsed through with ethyl acetate (25 mL) and washed with water (1 x 50 mL) then brine (1 x 50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-chloro-5-(3- nitropyridin-2-yl)benzoate (1.100 g, 61.0 %) as a yellow solid, m/z (ESI+) (M+H)+ = 293.25; HPLC tR = 2.31 min. 1H NMR (400 MHz, CDCl3) delta 3.94 (3H, s), 7.48 - 7.52 (IH, m), 7.54 - 7.56 (IH, m), 7.57 - 7.60 (IH, m), 8.10 - 8.11 (IH, m), 8.21 - 8.23 (IH, m), 8.87 - 8.89 (IH, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | palladium diacetate; triphenylphosphine; In tetrahydrofuran; at 65.0℃; | Intermediate 5: Methyl 2-chloro-5-(pyrimidin-2-yl)benzoate; A mixture of 2-bromopyrimidine (2.8 g, 17.63 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (4.2 g, 19.59 mmol), palladium acetate (0.22 g, 0.98 mmol) and triphenylphosphine (1.028 g, 3.92 mmol) in THF (80 mL) was heated at 65 0C overnight, then the reaction mixture was cooled, filtered through Celite and concentrated in vacuo. The residue was partitioned between EtOAc (200 mL) and saturated brine (200 mL) and the organic phase was dried, concentrated in vacuo, and then the residue was purified by chromatography on silica gel eluting with EtOAc/isohexane (0 - 50%) to give the title compound as a white solid (2.0 g, 42%): MS 249. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | Step A: 5-{7-amino-4-M -(piperidin-4-yl V 1 H-pyrazol-4-yllfuror2.3-clpyridin-2-yl)-2- chlorobenzoic acid hydrochlorideA suspension of 1-{4-[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1 H-pyrazol-1 - yl]piperidin-1-yl}ethanone (125 mg, 0.347 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (89.4 mg, 0.417 mmol), and Pd(PPh3)4 (40.1 mg, 0.0347 mmol) in 1.0 M aqueous sodium carbonate (1 .74 mL, 1.74 mmol) and 1 ,4-dioxane (1.63 mL) was heated to 120 C in a microwave for 30 min. The reaction mixture was then diluted with ethyl acetate (10 mL) and acidified with aqueous 1 N hydrochloric acid (5 mL), causing formation of a precipitate. The precipitate was collected by vacuum filtration and then triturated from DMSO and methanol (10 mL, -1 :10) to afford 55 mg (29%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.45 (d, J = 1.5 Hz, 1 H), 8.29 (s, 1 H), 8.22 (dd, J = 1.8, 8.3 Hz, 1 H), 8.00 (d, J = 8.1 Hz, 2H), 7.91 (s, 1 H), 7.75 (d, J = 8.6 Hz, 1 H), 6.56 (br s, 2H), 4.61 - 4.30 (m, 2H), 3.94 (br s, 1 H), 3.24 (br s, 1 H), 2.74 (br s, 1 H), 2.26 - 1.63 (m, 7H); MS (ESI): 480.10 [M+H]+; HPLC tR = 2.35 min (ZQ3, polar_4min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 150.0℃; for 0.5h;Microwave irradiation; | 00242] Step 2: A microwave vessel was charged with 2-(4-bromo-3-pyridin-4-yl- pyrazol-l-yl)-ethanol (180 mg, 0.669 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (172 mg, 0.803 mmol), PdCl2(PPh3)2 (27.3 mg, 0.033 mmol) under a nitrogen atmosphere. 1 ,4-Dioxane (3.5 mL) and saturated aqueous sodium bicarbonate (1.5 mL) were added. The vessel was capped and microwaved at 150C for 30 min. in a Biotage Initiator microwave instrument. The mixture was extracted with ethylacetate, dried over MgS04 and adsorbed onto silica gel. The methyl ester product was purfied bychromatography using a gradient of 50-100% Hexanes/ethylacetate to afford 54 mg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | [00223] Step 2: 2-Chloro-5-(2-phenyl-4-(2-methoxypyridin-4-yl)-lH-imidazol-5- yl)benzoic acid. A microwave vessel was charged with 2-phenyl-4-bromo-5-(2- methoxypyridin-4-yl)-lH-imidazole (55 mg, 0.167 mmol), 4-chloro-3- methoxycarbonylphenylboronic acid (39 mg, 0.183 mmol), PdCl2(PPh3)2 (6 mg, 0.008 mmol), and potassium carbonate (138 mg, 1 mmol) under nitrogen atmosphere. Degassed DME (1.6 mL) and water (0.4 mL) were added. The vessel was capped and microwaved at 150C for 30 min. in a Biotage Initiator microwave instrument. A IN aqueous solution of KOH (3 mL) was added and the mixture was further stirred overnight. The reaction mixture was filtered through celite and the filtrate was extracted with EtOAc (3x). The aqueous layer was isolated and acidified to pH 4.5 with concentrated HCl. The resulting precipitate was filtered, washed with water, and dried in vacuo to give 30 mg of the title compound as a light green solid (44% yield, two imidazole tautomers): main tautomer 1H NMR (DMSO- d6, ppm) delta 3.86 (s, 3H), 6.94 (broad s, 1H), 7.12 (d, 1H), 7.45 (t, 1H), 7.51-7.66 (m, 4H), 7.97-8.22 (m, 4H), 13.0 (broad s, 1H), 13.5 (broad s, 1H); [M+H+] m/z 406. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100.0℃; for 2.0h; | To a degassed solution of <strong>[874219-45-1](4-chloro-3-(methoxycarbonyl)phenyl)boronic acid</strong> (1.67 g, 7.79 mmol), 6-chloro-3-fluoropyridin-2-amine (1.51 g, 8.18 mmol), potassium carbonate (3.25 g, 23.4 mmol) and water (20 mL) in dioxane (95 mL) was added [1 ,1 - bis(diphenylphosphino)ferrocene] dichloropalladium(ll) (615 mg, 0.779 mmol). The reaction was stirred at 100C for 2 hours. The reaction was cooled and diluted with water (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (2 x 80mL), and the combined organic layers were washed with brine (100 mL), dried over MgS04 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 20% ethyl acetate in heptanes to afford the title compound (875 mg, 40%). 1 H NMR (400MHz, CDCI3): delta ppm 3.96 (s, 3H), 4.68 (br s, 2H), 7.06 (dd, 1 H), 7.28 (m, 1 H), 7.49 (d, 1 H), 7.95 (dd, 1 H), 8.36 (d, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrakis(triphenylphosphine) palladium(0); tripotassium phosphate; In tetrahydrofuran; water; at 85.0℃; for 1.5h;Inert atmosphere; Sonication; | Intermediate Ni, 7-bromo-5 -(1 -(tetrahydro-2H-pyran-4-yl)- 1H-pyrazol-5- yl)pyrrolo[2,1-J][1,2,4]triazin-4-amine, (0.325 g, 0.895 mmol), (4-chloro-3- (methoxycarbonyl)phenyl)boronic acid (0.326 g, 1.52 mmol) and K3P04 (0.76 mg, 3.58mmol) were combined in a 20 mL vial fitted with a septum and dissolved in a mixture of THF (6.51 mL) and water (0.65 mL). Argon was bubbled through the mixture while the vial was sonicated. Tetrakistriphenylphosphine palladium (0.1 g, 0.09 mmol) was added and the mixture was heated at 85 C. After 1.5 h, the reaction mixture was diluted with ethyl acetate (20 mL) and water (5 mL) and the layers were mixed and then separated (3times). The organic layers were mixed, dried over and concentrated. The residue was triturated with DCM, to obtain a white solid as the pure desired product (120 mg). Thefiltrate was concentrated and submitted for purification by silica gel column to obtain methyl 5-(4-amino-5-( 1 -(tetrahydro-2H-pyran-4-yl)- 1H-pyrazol-5-yl)pyrrolo [2,1 -J] [1,2,4]triazin-7-yl)-2-chlorobenzoate (323 mg, 0.7 13 mmol, 80% yield) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11099] 1.5 g (4.293 mmol) 1 -[2,6-dimethyl-4-[1 ,2,2,2-tet- rafluoro-1 -(trifluoromethyl)ethyl]phenyl]-pyrrole were dissolved in 60 ml of n-hexane, and 966 mg (4.3 mmol) of N-iodosuccinimide were added. Subsequently, the mixture was allowed to come to room temperature and stirred at room temperature for 6 days. Then a thrther 242 mg (1.1 mmol) of N-iodosuccinimide were added and the mixture was stirred at room temperature overnight. Subsequently, excess aqueous sodium hydrogen-sulphite solution and a little ethyl acetate were added. The organic phase was removed and first washed twice with aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. For purification, chromatography was effected using a cartridge containing 120 g of silica gel and a gradient proceeding from pure cyclohexane to 95:5 cyclohexane/ethyl acetate (v/v). 453 mg of a mixture of 80% 1-[2,6-dimethyl-4-[1,2,2,2- tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]-3-iodopyrrole and 16% 1 -[2,6-dimethyl-4-[1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]-2-iodopyrrole were obtained; jllOO] 998 mg (1.696 mmol) of a mixture of 80% 1-[2, 6-dimethyl-4-[1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl] phenyl]-3-iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ 1,2,2,2- tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]-2-iodopyrroleand 364 mg (1.7 mmol) of 4-chloro-3-(methoxy-carbonyl)phenylboronic acid were initially charged in 10 ml of 2-propanol. Thereafter, the air was displaced by argon, and5.2 ml of 1 molar aqueous sodium hydrogencarbonatesolution and 98 mg (0.085 mmol) of tetrakis(triphenylphosphine)palladium(0) were added under argon. Subsequently, the mixture was heated to reflux for 3 hours. For workup, the mixture was cooled a little, then concentrated on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and watet The organic phase was removed, washed with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 1.57 g of crude methyl 2-chloro-5-[1-[2,6-dim- ethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrrol-3-yl]benzoate were obtained. | ||
1.5 g (4.293 mmol) l-[2,6-dimethyl-4-[i,2,2,2-tetrafluoro-l -(trifl^ dissolved in 60 ml of n-hexane, and 966 mg (4.3 mmol) of N-iodosuccinimide were added. Subsequently, the mixture was allowed to come to room temperature and stirred at room temperature for 6 days. Then a further 242 mg (1.1 mmol) of N-iodosuccinimide were added and the mixture was stirred at room temperature overnight. Subsequently, excess aqueous sodium hydrogen-sulphite solution and a little ethyl acetate were added. The organic phase was removed and first washed twice with aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. For purification, chromatography was effected using a cartridge containing 120 g of silica gel and a gradient proceeding from pure cyclohexane to 95:5 eye lohexane/ ethyl acetate (v/v). 453 mg of a mixture of 80% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl] -3 -iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl]-2-iodopyrroie were obtained. 998 mg (1.696 mmol) of a mixture of 80% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl] -3 -iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ i ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl]-2-iodopyrrole and 364 mg (1.7 mmol) of 4-chloro-3-(methoxy- c arbony l)pheny lboronic acid were initially charged in 10 ml of 2-propanol. Thereafter, the air was displaced by argon, and 5.2 ml of 1 molar aqueous sodium hydrogencarbonate solution and 98 mg (0.085 mmol) of tetrakis(triphenylphosphine)palladium(0) were added under argon. Subsequently, the mixture was heated to reflux for 3 hours. For workup, the mixture was cooled a little, then concentrated on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was removed, washed with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 1.57 g of crude methyl 2-chloro-5-[l-[2,6- dimethyl-4-[l, 2,2,2 -tetrafluoro-l -(trifluoromethyl)ethyl]phenyl]pyrrol-3-yl]benzoate were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
628 mg | With pyridine; copper diacetate; In dichloromethane; at 20.0℃; for 20.0h;Molecular sieve; | 10967] 23 ml of dichloromethane, 353 mg (4.46 mmol) of pyridine, 609mg (3.35 mmol) of copper(II) acetate, 958mg (4.46 mmol) of 3-carboxymethyl-4-chlorophenylboronic acid and 760 mg (2.23 mmol) of (3-[2,6-dimethyl-4-[1,2,2, 2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] -1 H-pyrazolewere initially charged and then 1.1 g of freshly ground 3 A molecular sieve were added. The mixture was then stirred at room temperature for 20 hours. For workup, the mixture was filtered through a layer of kieselguhr and washed through with dichloromethane. The filtrate was concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected first using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 95:5 to 75:25 (v/v). The product-containing fractions were concentrated and chromatographed using a second cartridge containing 40 g of silica gel with toluene as eluent. After concentration, 628 mg of methyl 2-chloro-5- [3-[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro-1 -(trifluoromethyl) ethyl]phenyl]pyrazol-1 -yl]benzoate were obtained. |
628 mg | With pyridine; copper diacetate; In dichloromethane; at 20.0℃; for 20.0h;Molecular sieve; | 23 ml of dichloromethane, 353 mg (4.46 mmol) of pyridine, 609 mg (3.35 mmol) of copper(II) acetate, 958 mg (4.46 mmol) of 3-carboxymethyl-4-chlorophenylboronic acid and 760 mg (2.23 mmol) of (3- [2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] - 1 H-pyrazole were initially charged and then 1.1 g of freshly ground 3 A molecular sieve were added. The mixture was then stirred at room temperature for 20 hours. For workup, the mixture was filtered through a layer of kieselguhr and washed through with di chloromethane . The filtrate was concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected first using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ ethyl acetate of 95:5 to 75:25 (v/v). The product-containing fractions were concentrated and chromatographed using a second cartridge containing 40 g of silica gel with toluene as eluent. After concentration, 628 mg of methyl 2 -chloro-5-[3-[2,6-dimethyl-4-[ 1,2,2,2- tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrazol-l -yljbenzoate were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
151 mg | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In isopropyl alcohol;Reflux; | 10980] A 100 ml flask was initially charged with 280 mg (0.6 mmol) of 1 -[2,6-dimethyl-4-[1 ,2,2,2-tetrafluoro-1 -(tnfluoromethyl)ethyl]phenyl]-4-iodopyrazole and 0.129 g (0.60 mmol) of [4-chloro-3-(methoxycarbonyl)phenyl]bo- ronic acid in 21 ml of isopropanol, and lastly 1.84 ml (1.84 mmol) of degassed 1 molar sodium hydrogencarbonate solution were added. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. Then the mixture was heated to reflux. For workup, the mixture was concentrated on a rotary evaporator, and the residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. The residue was purified by chromatography with silica gel by means of a gradient from 90:10 to 70:30 (v/v) in cyclohexane/ethyl acetate, and gave 151 mg of methyl 2-chloro-5-[ 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrazol-4-yl]benzoate. |
151 mg | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In isopropyl alcohol;Reflux; | A 100 ml flask was initially charged with 280 mg (0.6 mmol) of 1 -[2,6-dimethyl-4-[ 1 ,2,2,2 -tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] -4-iodopyrazole and 0.129 g (0.60 mmol) of [4-chloro-3- (methoxycarbonyl)phenyl]boronic acid in 21 ml of isopropanol, and lastly 1.84 ml (1.84 mmol) of degassed 1 molar sodium hydrogenc arbonate solution were added. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. Then the mixture was heated to reflux. For workup, the mixture was concentrated on a rotary evaporator, and the residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. The residue was purified by chromatography with silica gel by means of a gradient from 90: 10 to 70:30 (v/'v) in eye lohexane/ethy 1 acetate, and gave 151 mg of methyl 2-chloro-5-[ 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro-l - (trifluoromethyl)ethyl]phenyl]pyrazol-4-yl]benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; cesium fluoride; In 1,4-dioxane; at 120.0℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation; | A microwave tube was charged with 5-(4-bromopyrazol-1-yl)-4-(difluoromethoxy)-1-methyl-3-[1 , 2,2,2- tetrafluoro-1-(trifluoromethyl)ethyl]pyrazole (0.130 g), (4-chloro-3-methoxycarbonyl-phenyl)boronic acid (0.067 g), Pd(dppf)2Cl2 (4.2 mg), anhydrous cesium fluoride (0.094 g) and anhydrous dioxane (1 mL). The tube was purched with argon, sealed up and heated in a microwave reacter to 120 C for 30 min. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was consecutively washed with water and brine, dried over magnesium sulfate and evaporated. The crude product was purified by flash chromatography (silica, cyclohexane / gradient of ethyl acetate from 0 to10%). LC-MS (Method A): tR = 1.22 min, m/z = 549 [M-1], 551 [M+1]. |
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Similarity: 0.83
A429740 [874219-46-2]
(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid
Similarity: 0.97
A203645 [603122-80-1]
(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.89
A206583 [603122-82-3]
(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.87
A105916 [913835-75-3]
2-Chloro-5-carboxyphenylboronic acid
Similarity: 0.83
A429740 [874219-46-2]
(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid
Similarity: 0.97
A203645 [603122-80-1]
(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.89
A206583 [603122-82-3]
(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.87
A105916 [913835-75-3]
2-Chloro-5-carboxyphenylboronic acid
Similarity: 0.83
A429740 [874219-46-2]
(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid
Similarity: 0.97
A203645 [603122-80-1]
(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.89
A206583 [603122-82-3]
(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid
Similarity: 0.87
A225713 [99769-19-4]
3-(Methoxycarbonyl)phenylboronic acid
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A256707 [177735-55-6]
(3,5-Bis(methoxycarbonyl)phenyl)boronic acid
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