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CAS No. : | 42860-04-8 | MDL No. : | MFCD00079732 |
Formula : | C7H4ClIO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SDRURVZKYHGDAP-UHFFFAOYSA-N |
M.W : | 282.46 | Pubchem ID : | 2757616 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 51.13 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.42 cm/s |
Log Po/w (iLOGP) : | 1.58 |
Log Po/w (XLOGP3) : | 3.67 |
Log Po/w (WLOGP) : | 2.64 |
Log Po/w (MLOGP) : | 3.09 |
Log Po/w (SILICOS-IT) : | 2.83 |
Consensus Log Po/w : | 2.76 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -4.24 |
Solubility : | 0.0162 mg/ml ; 0.0000574 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -4.14 |
Solubility : | 0.0203 mg/ml ; 0.000072 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -3.33 |
Solubility : | 0.131 mg/ml ; 0.000465 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.59 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA.TCI America, 9211 N. Harborgate Street, Portland, Oreg. 97203, USA...2-chloro-3,5-dinitrobenzoic acid; 2-chloro-3-fluorobenzoic acid; 2-chloro-4-fluorobenzoic acid; 2-chloro-6-fluoro-3-methylbenzoic acid; 4-chloro-3-iodobenzoic acid; 3-chloro-2-methyl-benzoic acid; 4-chloro-3-methylbenzoic acid; 4-chloro-2-nitrobenzoic acid; ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3 - 17h;Product distribution / selectivity; | *4-Chloro-3-iodobenzoyl chloride was prepared by dissolving <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (15.8 g, 56 mmol) in CH2Cl2 (40 mL) and treating with oxalyl chloride (4.1 mL, 46.7 mmol) and a catalytic amount of DMF (400 muL; vigorous gas evolution). The mixture was stirred at rt for 3 h. The reaction mixture was concentrated to afford a white solid, which was used without further purification.; B. 4-Chloro-3-iodo-benzoyl chloride. In a 5-L round-bottom flask equipped with a magnetic stirring bar and a gas scrubber, <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (275 g, 0.975 mol, 1.0 equiv) was suspended in CH2Cl2 (3 L) and DMF (2 mL, 0.026 mol, 2.5percent equiv) was added. Under N2 at 0° C., oxalyl chloride (93.5 mL, 1.1 mol, 1.1 equiv) was added dropwise over 1 h. The ice bath was removed and the reaction solution was stirred at rt for 16 h. The solvent was evaporated and the residue was used directly in the next reaction (-290 g, 100percent). |
100% | With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 17h;Inert atmosphere; | In a 5-L round-bottom flask equipped with a magnetic stirring bar and a gas scrubber, <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (275 g, 0.975 mol, 1.0 equiv) was suspended in CH2Cb (3 L) and DMF (2 mL, 0.026 mol, 2.5percent equiv) was added. Under N2 at 00C, oxalyl chloride (93.5 mL, 1.1 mol, 1.1 equiv) was added dropwise over 1 h. The ice bath was removed and the reaction solution was stirred at rt for 16 h. The solvent was evaporated and the residue was used directly in the next reaction (~290 g, 100percent). |
> 98% | With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 6h; | To an oven dried 50 mL round bottom flask was added 20 mL of dry methylene chloride (DCM), 2.35 g of 4-Chloro-3-iodo benzoic acid, and 3 drops of dimethyl formamide (DMF) to this solution was added drop wise by addition funnel 7.0 mL of 2.0M oxalyl chloride (CO2Cl2). The resultant mixture was stirred for 6 hours at room temperature. The solution was rotary evaporated to leave the neat acid chloride weighing 2.41 g (> 98percent yield). To this residue was added 20 mL of acetonitrile (ACN), 1.33 mL of diisopropyl ethyl amine, 1.25 mL (8.4 mmol, 0.45g) of 2-Methoxy-5-amino pyridine. The resultant solution was stirred for 15 hours and heated to reflux then quenched by the addition of 10 mL of brine and 10 mL of EtOAc. The product was taken up in 20 mL of EtOAc and washed with brine (1 x 15 mL), 1 M NaOH (2 x 25 mL), water (1 x 15 mL) and dried over MgSO4. The solution was rotary evaporated to leave a purplish waxy solid weighing 2.84 g (91.2percent crude yield). The solids were dissolved into 25 mL of warm methanol (MeOH) and left sealed for 24 hours. White- violet powder was recovered. This process repeated again to yield 1.96g (63.0percent) fluffy light violet solid. TLC was single spot rf 0.58 in 1 :1 Hexane/Ethyl Acetate. 1H NMR 400 MHz DMSO-d6: deltaH 9.01 (IH, br s), 8.24-6.77 (7H, m), 3.65 (3H, s); MS (ES+) m/z 389 (M+H); HPLC (214 nm), rt 4.22 min, 99.4percent. |
With thionyl chloride; for 1h;Heating / reflux; | The 4-chloro-3-iodo-benzoyl chloride used as a starting material was prepared as follows: EPO <DP n="39"/>Thionyl chloride (10 ml) was added to 4-Chloro-3-iodo-benzoic acid (1.13 g) and the mixure was refluxed for 1 hour. The reaction mixture was evaporated to give a solid (1.20 g);1H NMR: (400 MHz, CHLOROFORM-J) delta ppm 7.59 (d, 1 H) 8.03 (dd, 1 H) 8.57 (d, 1 H) | |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 1.5h; | Example 50: 4-Chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]- benzamideStep 1: 4-Chloro-3-iodo-N-[3-(trifluoromethyl)phenyl]benzamide4-Chloro-3-iodobenzoic acid (1.00 g, 0.00354 mol) was slurried in DCM (9 mL) and was cooled at 0 0C. To the mixture was added DMF (27 muL, 0.00035 mol) followed by oxalyl chloride (0.449 mL, 0.00531 mol). The resulting mixture was stirred at 0 0C for 30 minutes and then was warmed to 20 0C and was stirred for 60 minutes, by which time solution had occurred. LCMS of a sample quenched in methanol showed clean formation of the methyl ester (M+H 297/299, 3:1). The reaction mixture was concentrated to remove the excess oxalyl chloride providing acid chloride as a yellow solid acid. To the product was added DCM (1OmL), 3-(trifluoromethyl)benzenamine (0.484 mL, 0.00389 mol), then DIPEA (0.925 mL, 0.00531 mol). After 16 h, LCMS showed clean conversion to the expected M+H 426/428 (3:1). The reaction was quenched into 10percent citric acid, and the resulting mixture was extracted with DCM. The organic layer was washed with water, then <n="70"/>saturated NaHCCh, and dried (Na2SOzO. To the dried organic layer was added an equal volume of hexane and this mixture was concentrated using a rotary evaporator to remove most or all of the DCM. The resulting solid was filtered, rinsed with hexane and air dried to give 1.29 g off-white solid amide. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 3h; | 3-(4-Chloro-3-iodo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. To a solution of the above piperidone (10 g, 56 mmol) and p-toluenesulfonic acid (40 mg) in benzene (60 mL) was added morpholine (4.9 mL, 56 mmol). The reaction mixture was heated in a flask equipped with a condenser and a Dean-Stark trap at 90° C. for 16 h. The reaction mixture was cooled and concentrated to give the desired enamine as a beige solid, which was used without further purification. The enamine was dissolved in CH2Cl2 (40 mL), treated with TEA (9.4 mL, 67.2 mmol), and cooled to 0° C. To this solution was added 4-chloro-3-iodobenzoyl chloride* (16.9 g, 56 mmol). The reaction mixture was allowed to warm to rt, stirred for 14 h, and then concentrated. The resulting red oil was diluted with EtOH (56 mL) and treated with hydrazine (5.34 mL, 170 mmol) at 0° C. The resulting slurry was allowed to warm to rt and stirred for 16 h. EtOAc (120 mL) was added, and after 2 h the resulting precipitate was filtered and washed with additional EtOAc to afford the desired product as a white solid (8.80 g, 36percent). HPLC: Rt=6.08. MS (ESI): mass calcd. for C13H13ClIN3O2S, 437.7; m/z found, 438.1 [M+H]+. 1H NMR (DMSO-d6): 8.05 (d, J=1.9, 1H), 7.51 (d, J=8.3, 1H), 7.43 (dd, J=8.4, 1.9, 2H), 4.30 (s, 2H), 3.36 (t, J=5.8, 2H), 3.30 (br s, 1H), 2.86 (s, 3H), 2.69 (t, J=5.6, 2H).*Prepared by dissolving <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (15.8 g, 56 mmol) in CH2Cl2 (40 mL) and treating with oxalyl chloride (4.1 mL, 46.7 mmol) and a catalytic amount of DMF (0.40 mL; vigorous gas evolution). The mixture was stirred at rt for 3 h. The reaction mixture was concentrated to afford a white solid, which was used without further purification. | |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of 3-iodo-4-methylbenzoic acid 5?1 (262mg, 1.0mmol) in dry DCM (10mL) at 0°C was added oxalyl chloride (0.13mL, 1.5mmol) and 3 drops of dry DMF. The resulting reaction mixture was stirred at room temperature for 3h, and then the solvent was removed under reduced pressure. The crude product was used directly for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium iodide; sodium nitrite; In hydrogenchloride; water; acetone; | EXAMPLE 3A 4-chloro-3-iodobenzoic acid A solution of 3-amino-4-chlorobenzoic acid (8.6 g, 50 mmol) in 2:1 3M HCl/acetone (150 mL) at -3° C. was treated dropwise with sodium nitrite (3.8 g, 55 mmol) in water (30 mL), stirred for 30 minutes, treated with potassium iodide (14.5 g, 87.5 mmol) in water (50 mL), stirred for 15 minutes at 0° C. and at room temperature for 2 hours, and treated with water (500 mL) and excess NaHCO3 to provide a solid. The solid was collected by filtration and recrystallized from 20percent methanol/water to provide the desired product. MS (DCI/NH3) m/z 282 (M+H)+; 1H NMR (300 MHz, DMSO-d6) delta 13.35 (br s, 1H), 8.4 (d, 1H), 7.95 (dd, 1H), 7.7 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1-methyl-pyrrolidin-2-one; at 130℃; for 24h; | A mixture of 2,6-difluoro-N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzamide (0.35 g, 1 mmol), <strong>[42860-04-8]4-chloro-3-iodo-benzoic acid</strong> (c) (0.28 g, 1 mmol), PdCl2(PPh3)2 (80 mg, 0.1 mmol), and K2CO3 (0.14 g, 1 mmol) in NMP (4 mL) was stirred at 130° C. under nitrogen for 24 h. After being cooled, the mixture was poured into ice-water (50 mL). The resultant precipitation was collected by filtration, then washed with water. The solid material was dried and dissolved in DCM, undissolved material was filtered off. 0.12 g (30percent) of pure product, 6-chloro-4'-(2,6-difluoro-benzoylamino)-biphenyl-3-carboxylic acid, was obtained by silica gel chromatography (hexane/EtOAc to EtOAc/MeOH). 1H-NMR (CDCl3) delta ppm 7.30 (t, 2H, J=7), 7.40-8.15 (m, 9H); ESMS calcd for C20H12ClF2NO3: 387.0; found: 388.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1,2-dichloro-ethane; triethylamine; In water; ethyl acetate; N,N-dimethyl-formamide; | EXAMPLE 3B 4-chloro-3-iodo-N-methoxy-N-methylbenzamide A mixture of Example 3A (2.82 g, 10 mmol), EDC (2.11 g, 11 mmol), HOBt (1.68 g, 11 mmol), and N,O-dimethylhydroxylamine hydrochloride (1.26 g, 13 mmol) in DMF (30 mL) was stirred until all of the reagents dissolved, treated with triethylamine (2.54 mL, 18 mmol), stirred for 3 days at room temperature, treated with 1:1/ethyl acetate:water, stirred for 1 hour, poured into water, and extracted with ethyl acetate. The extract was washed sequentially with 2M Na2CO3, water, and brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 3:1/hexanes:ethyl acetate to provide the desired product. MS (DCI/NH3) m/z 343 (M+NH4)+; 1H NMR (300 MHz, CDCl3) delta 8.2 (d, 1H), 7.65 (dd, 1H), 7.5 (s, 1H), 3.55 (s, 3H), 3.35 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In tetrahydrofuran; methanol; ethyl acetate; | (i)4-chloro-3-iodobenzyl Alcohol Borane-THF complex (10 ml) was added dropwise over 20 minutes to a solution of <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (1.4 g) in THF (25 ml). The reaction mixture was stirred for 2 hours and then cooled (ice bath) and methanol (20 ml) was added cautiously. The solvent was removed and the residue was dissolved in methanol (10 ml) and stirred with aq. 2M sodium hydroxide (10 ml) for 2 hours. Ethyl acetate (50 ml) was added and the mixture was washed with saturated aq. sodium bicarbonate solution (50 ml). The aqueous extracts were washed with ethyl acetate (2*50 ml) and the combined ethyl acetate extracts were washed with water (50 ml) and brine (50 ml) and died. Removal of the solvent gave 4-chloro-3-iodobenzyl alcohol (1.15 g). NMR (CD3SOCD3): d 4.45 (d, 2H), 5.3 (t, 1H), 7.3 (m, 1H), 7.5 (m, 1H), 7.8 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.7% | With N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine;tris-(dibenzylideneacetone)dipalladium(0); In N,N-dimethyl-formamide; at 65℃; under 517.1619999999999 Torr; for 69h; | To a 1 L oven dried flask was added 225 mL of dry DMF, 9 niL of phenyl acetylene, 77 mL of DIEA, and 25 gm of 4- Chloro-3-iodo benzoic acid. The mixture was degassed by bubbling 10 psi N2 gas through a canula needle for 25 minutes. 2.02 gm of Pd2dba3 and 338 mg Of (O-ToIyI)3P were added and the resulting mixture stirred for 69 hours a 65 °C. The solution was cooled and 500 mL of saturated Na2S2O5 was added and shaken vigorously in a separatory funnel. The water portion was removed and a gelatinous film remained in the flask after pouring off of the organic layer. The organic layer was filtered through coarse filter paper into a 4 L Erlenmeyer flask to remove the remaining polymeric material and left to stand for 8 hours. No additional precipitation was observed. To the organic solution was added one liter of water followed by 500 mL of sodium metabisulfite. Precipitation of the product was observed and the solution cooled in an ice bath for an additional 2 hours. The precipitated solids were collected by filteration in a funnel and washed (3 x 500 mL) with ice water. The solids were dried over night under vacuum. 58.7 gm of large opaque crystals were recovered. The crystals were dissolved in 1 L of ethyl acetate (EtOAc) in a separatory funnel, washed (3 x brine, 3 x H2O), and dried with Na2SO4 for 1 hour. The solution was filtered and the solvent removed by rotary evaporatoration. Over night drying under vacuum resulted provided 18.57 g of product as plate like crystals (81.7percent yield). 1H NMR 400 MHz DMSO-d6: deltaH 11.52 (IH s), 7.88-7.20 (8H m); MS (ES") m/z 256 (M-H); HPLC (214 nm), rt 4.94 min, 99.8percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | To an oven dried 2L round bottom flask was added 525 mL of dry DMF, 225 mL of 2.0 M solution OfK2CO3, 16 gm of 4-biphenyl boronic acid, and 25 gm of 4-Chloro-3-iodo benzoic acid. The mixture was degassed for 25 minutes by bubbling 10 psi N2 gas through canula needle through the reaction solution. To the degassed solution was added 1.93 gm of Pd2dba3 and the resultant mixture was stirred for at 65 0C. After 24 hours, the solution was cooled and 300 mL of saturated Na2S2O5 was added. After vigorous mixing the mixture was filtered through a coarse sintered glass filter to remove the palladium. The solution was acidified with IN HCl which resulted in the formation of a precipitate. After one hour, the solid material was collected by filtration with a coarse sintered glass filter. The precipitate was washed with water (5 X 100 mL) to remove the residual solvents and 33.3 gm of a slightly yellow powder was isolated and then dried under vacuum for 12 hours. The powder was taken up in 150 mL of acetone and to it was added 45 mL of water. The resultant solution warmed until all of the solid material was dissolved. After cooling at 0 °C for 10 hours, the precipitate was collected by sintered glass filter and dried over night under vacuum to yield 25.5 gm of flat white flakes were recovered for a 93.4percent yield. 1H NMR 400 MHz DMSO-d6: deltaH 7.91-7.29 (12H, m); MS (ES") m/z 308 (M+); HPLC (214 nm), rt 6.64 min, 99.0percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium borohydrid; iodine; In tetrahydrofuran; | a) Preparation of 2-chloro-1-iodo-5-hydroxymethylbenzene according to J. Org. Chem., 1991, 56, 5964-5965, from the corresponding commercial benzoic acid. 5.02 g of sodium borohydride are added portionwise and then 14.6 g of iodine, in solution in 50 ml of tetrahydrofuran, are added very slowly to 25 g of <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> in solution in 200 ml of tetrahydrofuran at 0° C. The reaction mixture is stirred for 2 hours at room temperature and then at 35° C. for 30 minutes. Hydrolysis is carried out at 10° C. with a 0.5N hydrochloric acid solution and extraction is carried out with ethyl acetate. The organic phase is separated by settling and then treated with an aqueous sodium bisulphite solution and then with water. The organic phase is dried over anhydrous sodium sulphate and the solvents are evaporated under reduced pressure. The expected compound is obtained by distillation; B.p.=109° C. under 3 Pa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Example 1 Synthetic 4-Chloro-3-iodo-N-(6-methoxy-pyridin-3-yl)-benzamide (3a) To a solution of <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (20 g, 70.8 mmol), EDC*HCl (15 g 78.2 mmol) and HOBt (11 g, 78 mmol) in 500 mL of dry dichloromethane was added DIEA (27 mL, 156 mmol). The mixture was stirred for 15 minutes at which time 5-amino-2-methoxy pyridine (10 g, 79 mmol) was added. The reaction stirred at room temperature for 12 hours. The reaction was washed with 600 mL of water. The DCM layer was separated, and the product precipitated out of solution. Pure product 3a was obtained upon filtration and dried in a vacuum oven at 50° C. to yield 21 g (78percent) of a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;palladium diacetate; triphenylphosphine; In water; acetonitrile; at 50℃; for 20h;Product distribution / selectivity; | The title compound was prepared using methods analogous to those in Representative Procedure A. 1H NMR (600 MHz, CDCl3, delta): 13.2 (br s, 1H), 9.60 (s, 1H), 7.89 (dd, J=8.3, 2.1 Hz, 1H), 7.81 (d, J=2.1 Hz, 1H), 7.65 (d, J=8.3 Hz, 1H), 7.24 (ddd, J=9.1, 7.5, 1.7 Hz, 1H), 7.12 (dd, J=7.5, 1.7 Hz, 1H), 6.95 (dd, J=8.2, 0.9 Hz, 1H), 6.88 (td, J=7.4, 1.1 Hz, 1H); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a 25 mL sterile centrifuge tube was added 10 mL of DCM. To this was added 1.0 g of Irori Wang resin (1.36 mmol/g loading) and 1.62 g of 2-(9H-Fluoren-9- ylmethoxycarbonylamino)-indan-2-carboxylic acid, 803 muL DCC, 597 mg HOBT, and 2 mg of dimethylaminopyridine (DMAP). The solution was capped and gentle agitated for 20 hours. A small sample of the resin (10.8 mg) was washed (2 x DMF, 2 x DCM, 2 x Et2O) and dried in a vacuum for 30 minutes. To this resin was added 1 mL of 30percent piperdine in DMF for 30 minutes to remove the FMOC protecting group. 1 mL of DMF was added and four 100 muL samples were analyzed by UV to determine the FMOC content. The loading was determined to be 0.369 mmol/g (42percent of theoretical). The remaining resin was added to 20 mL of 30percent piperdine/DMF solution for one hour, washed (2 x DMF, 2 x DCM, 2 x Et2O) and dried under vacuum for 12 hours. To a 25 mL sterile centrifuge tube was added 36 mL of DCM. To this was added the 1 g of indene loaded resin, 1.15 g of 4-Chloro-3-iodo benzoic acid, 2.09 g PyBOP, and 2.13 mL DIEA. After 2 hours the resin was rinsed and a bromophenyl blue solution added to 3 mg of beads. Primary amine was detected and the coupling reaction was repeated using 20 mL of N-methylproline (NMP), 1 g of indene loaded resin, 1.2 g 4-Chloro-3-Iodo benzoic acid, 1.6 g HATU, 0.56 g HOAT, and 2.1 mL of DIEA. After 15 hours of agitation, a second bromophenyl blue test was performed and no amine detected.[0152] In a separate 25 mL pear shaped flask was added 10 mL of acetone, 1 g of Iodo phenyl-indene loaded resin, 1.98 g 4-Biphenyl boronic acid, 0.25 g Pd2dba3, and 1 mL of 2M K2CO3. The resultant mixture was heated to 65 °C for 22 hours. The resin was filtered and washed (2 x Na2SO5, 2 x H2O, 2 x DMF, 2 x CH3OH, 2 x DCM, 1 x EtOAc, 2 x Et2O) and dried in a vacuum for 10 hours. Cleavage of the product from the resin was effected by the addition of 5 mL TFA, 0.10 ml, H2O, 0.10 mL DCM in a 15 mL enclosed fritted funnel for 20 minutes. The filtrate was removed, the resin washed (3 x 15 mL DCM), and all fractions collected. Rotary evaporation of the filtrate left 156 mg of a crude product as an oil (24percent yield). 16 mg of the crude oil was purified by semipreparative HPLC to obtain 10.2 mg pure product. 1H NMR 400 MHz DMSO-d6: deltaH 12.5 (IH br s), 8.93 (IH s), 7.94-7.10 (16H, m), 4.61 (2H, d, J = 13.5 Hz), 3.38 (2H, d, J = 13.6 Hz); MS (ES') m/z 468 (M-H); HPLC (214 nm), rt 6.90 min, 99.4percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | sulfuric acid;Reflux; | Step 1. Methyl 4-chloro-3-iodobenzoate A solution of <strong>[42860-04-8]4-chloro-3-iodobenzoic acid</strong> (500 mg, 1.77 mmol, 1.00 equiv), methanol (20 mL), and concentrated sulfuric acid (0.35 g, 2.00 equiv) was heated to reflux overnight in an oil bath. The resulting mixture was concentrated in vacuo and diluted with 50 mL of ethyl acetate. The organic layer was washed with 3.x.20 mL of water and 3.x.20 mL of saturated aqueous sodium carbonate. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo, resulting in 0.52 g (99percent) of methyl 4-chloro-3-iodobenzoate as a white solid. |
95% | With sulfuric acid; at 80℃; for 4h; | Compound 50.1. Methyl 4-chloro-3-iodo-benzoate. 4-Chloro-3-iodo-benzoic acid (5.31 g, 18.8 mmol) was dissolved in methanol (50 mL) and concentrated sulfuric acid (3 raL) was carefully added. The solution was stirred at 80 °C for 4 hours, then cooled to room temperature and the volatile organics were removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and water (50 mL) and the organic layer was washed with brine, dried (Na2S04), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (Si02; 0- 10 percent EtOAc in hexanes) to yield 5.32 g (95 percent) of the title compound as an oil. H NMR (400 MHz, Chloroform-d) delta 8.54 (d, J 1H), 7. |
95% | With sulfuric acid; at 80℃; for 4h; | Compound 50.1. Methyl 4-chloro-3-iodo-benzoate. 4-Chloro-3-iodo-benzoic acid (5.31 g, 18.8 mmol) was dissolved in methanol (50 mL) and concentrated sulfuric acid (3 mL) was carefully added. The solution was stirred at 80 °C for 4 hours, then cooled to room temperature and the volatile organics were removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and water (50 mL) and the organic layer was washed with brine, dried ( a2S04), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (SiC^; 0-10 percent EtOAc in hexanes) to yield 5.32 g (95 percent) of the title compound as an oil. XH NMR (400 MHz, Chloroform-d) delta 8.54 (d, J 1H), 7.96 (dd, J= 8.4, 2.0 Hz, 1H), 7.53 (d, J= 8.4 Hz, 1H), 3.94 (s, 3H) |
90% | With thionyl chloride;Cooling with ice; Reflux; | To a solution of 4-chloro-3-iodobenzoicacid 1 (35.4 mmol) in100 mL anhydrous methanol, thionyl chloride (53 mmol) was addeddropwise in ice-bath, and the solution was kept stirring at room temperaturefor 10 minutes. Then the mixture was refluxed untill the material was consumedcompletely (monitored by TLC).The cooled reaction was concentrated under vacuum. The residue was dissolved inEtOAc (60 mL), washed with water, brine, dried over anhydrous Na2SO4and concentrated under vacuum to give methyl4-chloro-3-iodobenzoate 2 as white solid with 90percent yield. 1HNMR (400 MHz, CDCl3) delta 8.51 (d, J= 1.6 Hz, 1H), 7.94 (dd, J1= 8.4 Hz, J2 =2.0 Hz, 1H), 7.51 (d, J = 8.0 Hz,1H), 3.92 (s, 3H). |
Tags: 42860-04-8 synthesis path| 42860-04-8 SDS| 42860-04-8 COA| 42860-04-8 purity| 42860-04-8 application| 42860-04-8 NMR| 42860-04-8 COA| 42860-04-8 structure
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Code | Phrase |
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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. |
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P282 | Wear cold insulating gloves/face shield/eye protection. |
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Response | |
Code | Phrase |
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P306 | IF ON CLOTHING: |
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P321 | |
P322 | |
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P337 | If eye irritation persists: |
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P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
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P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
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P378 | |
P380 | Evacuate area. |
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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. |
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
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P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
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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: |
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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 |
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P402 | Store in a dry place. |
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P406 | Store in corrosive resistant/ container with a resistant inner liner. |
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Disposal | |
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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 |
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H223 | Flammable aerosol |
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H228 | Flammable solid |
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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 |
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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 |
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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.
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