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Structure of 2268-05-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 2268-05-5 |
Formula : | C6H3Cl2F |
M.W : | 164.99 |
SMILES Code : | C1=CC=C(C(=C1Cl)F)Cl |
MDL No. : | MFCD00010307 |
InChI Key : | JORVCRLRRRRLFI-UHFFFAOYSA-N |
Pubchem ID : | 137520 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H228-H315-H319-H335 |
Precautionary Statements: | P210-P261 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.57 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.42 |
Solubility | 0.0623 mg/ml ; 0.000378 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.95 |
Solubility | 0.183 mg/ml ; 0.00111 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.9 |
Solubility | 0.0208 mg/ml ; 0.000126 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
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) |
Yes |
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 |
-4.98 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 |
2.0 |
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) |
1.55 |
* 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 |
---|---|---|
94% | With sulfuric acid; nitric acid; In dichloromethane; at 40℃; under 5250.53 Torr; | <strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> was dissolved in 20% methylene chloride,Flat streamerUsed to enter the nitric acid,Set the flow rate to11.9ml/min corresponding to nitric acid 0.27ml ,Flat streamer 13 used to enter the sulfuric acid,Set the flow rate of 25.2ml, equivalent to sulfuric acid 0.46mol / min,Sulfuric acid and nitric acid in a microchannel reactor1 to complete the mix,Flat streamerC used to enter<strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> in methylene chloride at a flow rate of 38.5 ml / min,Equivalent to <strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> 0.27 mol / min,<strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> and mixed acid in the microchannel reactor 2 to start the mixing reaction,At this time, the molar ratio of 2,6 - dichlorofluorobenzene to nitric acid was 1: 1, the reaction temperature was 40 C,The reaction residence time in each microchannel reactor was 33 s and the system pressure was 0.7 MPa.After the product was withdrawn from the outlet, the conversion of <strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> was 100% after extraction, washing and washing, and the selectivity of 2,4-dichloro-3-fluoronitrobenzene was 94%. |
With sulfuric acid; nitric acid; sodium sulfate; at 50 - 70℃; for 2h; | Weigh a certain amount of <strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> in the flask,Add some concentrated sulfuric acid and a small amount of anhydrous Na2SO4 under heating and stirring, and stir to 60-70 C to dissolve completely.Then cool to 50 ~ 55 C, start slowly adding mixed acid,Reaction 2 h,After the reaction is completed, let stand for another 3 to 4 hours.The product was rinsed with 10% NaOH and cold water.The aqueous layer was extracted with anhydrous ethyl ether and dried over anhydrous sodium sulfate.The desiccant is filtered off, and the ether is recovered by atmospheric distillation.Distilling under reduced pressure to take the middle fraction,Distillation temperature 117 ~ 119 C,Obtained a pale yellow oil which is 2,6-dichloro-3-nitrofluorobenzene.The reaction temperature is controlled at 50 to 55 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 2,2,6,6-tetramethylpiperidine (20.07 ml_, 1 18 mmol) dissolved in Tetrahydrofuran (THF) (300 ml.) at 0 0C was added nBuLi (73.9 ml_, 118 mmol) dropwise. The solution was stirred at 0 0C for 10 minutes and cooled to -78 0C. 1 ,3- dichloro-2-fluorobenzene (15 g, 91 mmol, commercially available from e.g. Sigma- Aldrich, Apollo or Alfa Aesar) dissolved in Tetrahydrofuran (THF) (30 ml.) was added dropwise and the solution was stirred at -78 0C for 1 hour. The solution was poured on to dry ice (xs) that had been previously washed with tetrahydrofuran (3 x 100 ml.) and stirred to room temperature over 3 hours. Solvents were removed in vacuo to afford a white solid. The solid was combined with solid isolated from method a) and partitioned between ethyl acetate (200 ml.) and 2N Hydrochloric acid. The aqueous solution was extracted with ethyl acetate (3 x 100 ml_); the combined extracts were washed with brine (50 ml.) and concentrated to a crude solid. The crude solid was recrystalised from cyclohexane/toluene to afford the product 19.03 g. LC/MS = 207/209 (M-H)-, retention time = 0.90 minutes (2 minute method). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydrogencarbonate; potassium carbonate; In water; ethyl acetate; acetone; | EXAMPLE 20 2-[3-(2,6-Dichloro-phenoxy)4-ethyl-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide (I-20) step 1-To a solution of 12a (0.200 g; 0.960 mmol) and NMP (4 mL) was added K2CO3 (0.398 g; 2.88 mmol) and <strong>[2268-05-5]1,3-dichloro-2-fluoro-benzene</strong> (0.174 g; 1.056 mmol). The reaction was heated to 120 C. and monitored by TLC. After 8 h the reaction was cooled to RT and 10% HCl was added. The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine. The extracts were dried (Na2SO4) filtered and evaporated. The crude product was purified by SiO2 chromatography eluding with a hexane/EtOAc gradient (0 to 40% EtOAc) to afford 144. steps 2 and 3-Hydrolysis and formation of the acid chloride were carried as described in step 7and 8 of Example 1 and used without additional purification. step 4-The acid chloride from step 3 (0.14 mmol) was dissolved in acetone (2 mL) and the flask was purged with nitrogen. NaHCO3 (0.024 g; 0.28 mmol) was added followed by 4-amino-benzenesulfonamide (0.024 g; 0.14 mmol) and water (4 mL). The mixture was sonicated for 5 min and allowed to stir for 12 h at RT. The reaction mixture was filtered and the crude product was washed sequentially with water and diethyl ether to afford I-20. Compound I-23 was prepared in the same manner except 4-amino-benzenesulfonamide was replaced by 2-chloro-phenylamine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.5% | n a 250 ml four-necked flask, 64 g of 98% concentrated sulfuric acid was charged(0.606 mol) of <strong>[2268-05-5]2,6-dichlorofluorobenzene</strong> was added dropwise to a stirred solution of 33 g of 98% concentrated sulfuric acid at 20 to 25 CMixed with 39 g of 98% concentrated nitric acid, 2.5 hThe addition is complete.After warming up to 40 ~ 45 C and heat 1.5 hours. After the end of the washing, to neutral, organic subtractionPressure dehydration after use.In a 250 ml four-necked flask285gSulfolane and87g (1.5mol) KF, after dehydration by adding the last step nitration products,In 195 ± 5 C heat 5h, vacuum distillation of the solvent and then distillation 2,3,4-trifluoronitrobenzene 91. 7g,The content was 99.8% and the yield was 85.5% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 120℃; for 8h; | To a solution of 12a (0.200 g; 0.960 mmol) and NMP (4 mL) was added K2CO3 (0.398 g; 2.88 mmol) and <strong>[2268-05-5]1,3-dichloro-2-fluoro-benzene</strong> (0.174 g; 1.056 mmol). The reaction was heated to 120 C. and monitored by TLC. After 8 h the reaction was cooled to RT and 10% HCl was added. The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine. The extracts were dried (Na2SO4) filtered and evaporated. The crude product was purified by SiO2 chromatography eluting with a hexane/EtOAc gradient (0 to 40% EtOAc) to afford 144. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 120℃; | To a solution of 19 (3.0 g, 14.0 mmol) in NMP (20 mL) was added K2CO3 (5.80 g, 41.9 mmol) and <strong>[2268-05-5]1,3-dichloro-2-fluoro-benzene</strong> (26, 2.31 g, 14.0 mmol). The reaction was heated to 120 C. overnight. The reaction mixture was cooled to RT, diluted with H2O and extracted 3 times with EtOAc. The combined extracts were washed with H2O and brine, dried (Na2SO4), filtered and evaporated in vacuo to afford 27 which was used in subsequent steps without further purifications. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.5% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 2-(((2,6-diisopropylphenyl)imino)methyl)pyridine; In n-heptane; for 18h;Reflux; | Step 1: Preparation of 2-(3,5-dichloro-4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 4,4,4',4',5,5,5',5'-Octamethyl[2,2'-bi-1,3,2-dioxaborolane] (2.0 g, 7.88 mmol), 2,6-bis(1-methylethyl)-N-(2-pyridinylmethylene)benzenamine (0.080 g, 0.30 mmol), and bis(1,5-cyclooctadiene)diiridium dichloride (0.132 g, 0.20 mmol) were added to a solution of <strong>[2268-05-5]1,3-dichloro-2-fluorobenzene</strong> (2.0 g, 12.12 mmol) in heptane (40 mL). The reaction mixture turned from yellow to forest green to brick red within the first minute. The reaction mixture was refluxed for 18 h. The mixture was then partitioned between EA and water, and the aqueous extract was washed twice with EA. The organic extracts were combined, dried over Na2SO4, and concentrated under reduced pressure. The solid residue was purified by chromatography on silica gel eluted with PE-EA (10:1) to give 2-(3,5-dichloro-4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.56 g, yield 72.5%) as a white solid. 1H NMR (500 MHz, CDCl3): delta 7.646 (d, J=6.5 Hz, 2H), 1.266 (s, 12H) ppm. |
With 2-(((2,6-diisopropylphenyl)imino)methyl)pyridine;bis(1,5-cyclooctadiene)diiridium(I) dichloride; In n-heptane; for 18h;Heating / reflux; | 4,4,4>,4>,5,5,5',5'-Octamethyl[2,2'-bi-1,3,2-dioxaborolane] (10.0 g, 39.4 mmol), 2,6- bis(l-methylethyl)-N-(2-pyridinylmethylene)benzenamine (0.40 g, 1.5 mmol), and i-mu- chlorobis[(1,2,5,6- eta)-1,5-cyclooctadiene]diiridium (0.50 g, 1.0 mmol) were added to a solution of <strong>[2268-05-5]1,3-dichloro-2-fluorobenzene</strong> (10.0 g, 60.6 mmol) in heptane (200 mL). The reaction mixture turned from yellow to forest green to brick red within the first minute. The reaction mixture was heated to reflux for 18 h. The mixture was then partitioned between ethyl acetate and water, and the aqueous extract was washed twice with ethyl acetate. The organic extracts were combined, dried over MgSOphi and concentrated under reduced pressure. The solid residue was purified by chromatography on silica gel by elution with ethyl acetate/hexane to afford the title compound as a solid (11.0 g). 1H NMR (CDCl3) delta 7.72 (d, 2H), 1.33 (s, 12H). | |
With 2-(((2,6-diisopropylphenyl)imino)methyl)pyridine;bis(1,5-cyclooctadiene)diiridium(I) dichloride; In n-heptane; for 18h;Heating / reflux; | Step B: Preparation of 2-(3,5-dichloro-4-fluorophenyl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane; M^'^'^^^'^'-Octamethyip^'-bi-l^^-dioxaborolane] (10.0 g, 39.4 mmol), 2,6- bis(l-methylethyl)-iV-(2-pyridinylmethylene)benzenamine (0.40 g, 1.5 mmol), and di-mu- chlorobis[(l,2,5,6-?7)-l,5-cyclooctadiene]diiridium (0.50 g, 1.0 mmol) were added to a solution of l,3-dichloro-2-fluorobenzene (10.0 g, 60.6 mmol) in heptane (200 mL). The reaction mixture turned from yellow to forest green to brick red within the first minute. The reaction mixture was heated to reflux for 18 h. The mixture was then partitioned between ethyl acetate and water, and the aqueous extract was washed twice with ethyl acetate. The <n="13"/>organic extracts were combined, dried over MgSC«4, and concentrated under reduced pressure. The solid residue was purified by chromatography on silica gel by elution with ethyl acetate/hexane to afford the title compound as a solid (11.0 g). 1H NMR (CDCl3) delta 7.72 (d, 2H), 1.33 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11%; 3.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 20h; | Step 3 :4-Chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridineA mixture of 4-chloro-lH-pyrazolo[4,3-c]pyridine (150 mg, 0.990 mmol), l,6-dichloro-2-fluorobenzene (300 mg, 1.80 mmol) and potassium carbonate (450 mg, 3.26 mmol) in dry DMF (3.0 mL) was heated at 85 °C for 20 h. The reaction was quenched with water (30 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic extracts were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified on silica gel (ethyl acetate : petroleum ether = 1 : 10) to give 4-chloro-2- (2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine as a white solid (10 mg, 3.5percent yield) and 4-chloro-l-(2,6- dichlorophenyl)-lH-pyrazolo[4,3-c]pyridine as a white solid (30 mg, 11percent yield).4-Chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine: 3/4-NMR (CDC13): delta 8.31 (d, J = 0.5 Hz, 1H), 8.13 (d, J= 6.0 Hz, 1H), 7.64-7.56 (m, 3H), 7.49 (m, 1H). LCMS(ESI) m/z: 298.0 [M+H+]. 4-Chloro-l-(2,6-dichlorophenyl)-lH-pyrazolo[4,3-c]pyridine, 3/4-NMR (CDC13): delta 8.44 (d, J = 0.5 Hz, 1H), 8.24 (d, J= 6.0 Hz, 1H), 7.57-7.47 (m, 3H), 7.00 (d, J = 6.0 Hz, 1H). LCMS(ESI) m/z: 298.0 [M+H+]. |
11%; 3.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 20h; | A mixture of 4-chloro-1H-pyrazolo[4,3-c]pyridine (150 mg, 0.990mmol), 1,6-dichloro-2-fluorobenzene (300mg, 1.80mmol) andpotassium carbonate(450 mg, 3.26mmol) in dry DMF(3.0 mL)was heated at 85 °C for 20 h.The reaction was quenched with water (30 mL) and extracted withethyl acetate (3 x 20 mL).The combined organic extracts were washed with brine, dried over Na2SO4andconcentrated under reduced pressure.The residue was purified on silica gel(ethylacetate :petroleum ether = 1 : 10)to givethe desired productas a white solid(10 mg, 3.5percent yield)anditsregio-isomeras awhitesolid(30 mg, 11percent yield).4-Chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine:1H-NMR(CDCl3):delta8.31 (d,J= 0.5 Hz,1H), 8.13 (d,J= 6.0 Hz,1H), 7.64-7.56(m, 3H), 7.49 (m, 1H).LCMS(ESI) m/z: 298.0[M+H+].4-Chloro-1-(2,6-dichlorophenyl)-1H-pyrazolo[4,3-c]pyridine,1H-NMR(CDCl3):delta8.44(d,J= 0.5 Hz,1H), 8.24(d,J= 6.0 Hz,1H), 7.57 -7.47(m, 3H), 7.00(d,J= 6.0 Hz,1H).LCMS(ESI) m/z: 298.0[M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | Example 41 Preparation of 2-(2,4-dichloro-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To a 200 mL flask charged with THF (20 mL) was added <strong>[2268-05-5]1,3-dichloro-2-fluorobenzene</strong> (3 g, 18.18 mmol). The reaction mixture was cooled to -78 C. in a dry ice/acetone bath. 2.5 M n-Butyllithium in hexanes (1.4 g, 24.8 mmol) was added slowly down the sides of the flask. After allowing the reaction mixture to stir for 1 hour at -78 C., 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.06 g, 21.82 mmol) in a solution of THF (10 mL) was added all at once. The reaction mixture was allowed to warm slowly to room temperature overnight. The solution was then neutralized with 2N HCl and diluted with water (200 mL). The aqueous layer was washed with Et2O (200 mL*2). The organic layers were combined, dried over MgSO4, and filtered. The solution was concentrated onto 8 g of Celite using EtOAc as solvent. The impregnated Celite was loaded onto a silica gel column and purified by flash chromatography using 0-30% EtOAc:hexanes to yield 2-(2,4-dichloro-3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as a clear oil (1.8 g, 34%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sulfuric acid; palladium diacetate; zinc; XPhos; In N,N-dimethyl acetamide; at 120℃; for 3h; | Palladium-Catalysed Cyanation of Chlorofluoroaromatic Compounds (0091) (0092) Procedure analogous to M. Shevlin, Tetrahedron Letters, 2010, 51, 4833. Catalyst Solution: (0093) 3 ml of a mixture of 2.81 g of concentrated sulfuric acid in 28 ml of N,N-dimethylacetamide are added to a solution of 2.73 g (5.7 mmol) of X-Phos and 643 mg (2.9 mmol) of palladium(II) acetate in 60 ml of N,N-dimethylacetamide, and the mixture is stirred at 80 C. for 30 min., during which a dark-brown solution forms. (0094) 1 ml of the catalyst solution is added to a vigorously stirred mixture of 23.6 g (143 mmol) of <strong>[2268-05-5]1,3-dichloro-2-fluorobenzene</strong>[2268-05-5], 20.2 g (172 mmol) of zinc(II) cyanide, 750 mg (11.5 mmol) of zinc dust and 280 ml of N,N-dimethylacetamide, and the mixture is stirred at 120 C. for 3 h. When the reaction is complete, the solvent is substantially removed in vacuo, the residue is taken up in 500 ml of ethyl acetate, salts remaining are filtered off, the filtrate is washed three times with 300 ml of water and once with 300 ml of sodium chloride solution and dried over magnesium sulfate. The residue remaining after removal of the solvent is recrystallised twice from cyclohexane. Yield: 15.8 g (109 mmol) 76%. Purity: about 97% according to 1H-NMR. |
76% | With sulfuric acid; palladium diacetate; zinc; XPhos; In N,N-dimethyl acetamide; at 80 - 120℃; for 3h; | 3 ml of a mixture of 2.81 g of concentrated sulfuric acid in 28 ml N, N- dimethylacetamide were added to a solution of 2.73 g (5.7 mmol) X-Phos and 643 mg (2.9 mmol) of palladium (II) acetate in 60 ml Nu, Nu-dimethylacetamide , and the mixture is stirred at 80 C, for 30 min during which a dark brown solution forms. 1ml of the catalyst solution is added to a vigorously stirred mixture of 23.6 g (143 mmol) 1, 3-dichloro-2-fluoro-benzene [2268-05-5], 20.2 g (172 mmol) of zinc (II) cyanide, 750 mg (1 1 .5 mmol ) zinc dust and 280 ml Nu, Nu-dimethylacetamide, and the mixture is stirred for 120 C for 3 h. After the reaction, the solvent is largely removed under vacuum, the residue is taken up in 500 ml of ethyl acetate, , the filtrate is washed three times with saline 300 ml of water and once with 300 ml and dried over magnesium sulfate. The remaining after the removal of the solvent residue is recrystallized twice from cyclohexane. Yield: 15.8 g (109 mmol) 76%. 1 H-NMR. Purity: about 97% pure n 1 H-NMR |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 1-methyl-pyrrolidin-2-one; potassium carbonate; at 200℃; for 4h;Sealed tube; Inert atmosphere; | tert-Butyl 4-(3-oxo-2,3-dihydro-1H-indazol-1-yl)benzoate (300 mg; 0.97 mmol; 1.00 eq.), <strong>[2268-05-5]1,3-dichloro-2-fluoro-benzene</strong> (1.59 g; 9.67 mmol; 10.0 eq.), potassium carbonate -325Mesh (267 mg; 1.93 mmol; 2.00 eq.) and 1-methyl-2-pyrrolidinone (5.00 mL) were stirred at 200 C for 4 hours in a sealed tube. The reaction mixture was cooled, diluted in ethyl acetate (50 mL) and water (50 mL). The pH of the aqueous layer was adjusted to 1 using a 3 M solution of hydrochloric acid. The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were dried over MgSO4,concentrated and purified by preparative HPLC.4-(3-(2,6-dichlorophenoxy)-1H-indazol-1-yl)benzoic acid was isolated as a beige solid (120 mg; 29.0 %).1H NMR (DMSO-d6) delta: 7.47 - 7.35 (m, 2H), 7.75 - 7.61 (m, 5H), 7.92 - 7.86 (m, 1H), 8.00 (d,J =8.7 Hz, 1H), 8.10 - 8.04 (m, 2H), 13.02 (s, 1H).MS-ESIm/z399 [MH+]. |
Tags: 2268-05-5 synthesis path| 2268-05-5 SDS| 2268-05-5 COA| 2268-05-5 purity| 2268-05-5 application| 2268-05-5 NMR| 2268-05-5 COA| 2268-05-5 structure
A123698 [36556-33-9]
1,3,5-Trichloro-2-fluorobenzene
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A362240 [2367-80-8]
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A123698 [36556-33-9]
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A362240 [2367-80-8]
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A123698 [36556-33-9]
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A362240 [2367-80-8]
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A322836 [2106-40-3]
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