Structure of 871329-84-9
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CAS No. : | 871329-84-9 |
Formula : | C7H6BFO4 |
M.W : | 183.93 |
SMILES Code : | OB(O)C1=CC(F)=CC(=C1)C(O)=O |
MDL No. : | MFCD07363791 |
InChI Key : | APHPXZJIUTVQNC-UHFFFAOYSA-N |
Pubchem ID : | 44717205 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With palladium diacetate; sodium carbonate; triphenylphosphine; In propan-1-ol; water; at 95.0℃;Inert atmosphere; | In a 4 mL vial, palladium acetate (4.9 mg, 0.022 mmol), triphenylphosphine (12.1 mg, 0.046 mmol), 2M aqueous solution of sodium carbonate (0.96 ml, 1.920 mmol) and water (0.3 ml, 16.65 mmol) were successively added to a mixture of 2-bromo-5-methoxypyridine (0.1 ml, 0.814 mmol) and <strong>[871329-84-9]3-carboxy-5-fluorophenylboronic acid</strong> (148 mg, 0.805 mmol) in 1-propanol (1.5 ml, 19.97 mmol) under nitrogen. The mixture was stirred at 95 C overnight. The mixture was quenched with IN HCl and the product was extracted three times with AcOEt. The aqueous phase was neutralized to pH 7 with NaOH 10% and extracted twice with AcOEt. The combined organic layers were washed once with water, once with brine, dried over anh. Na2SO4 and concentrated. The white solid in suspension in aqueous phase was filtrated and the two products were mixed together to give the title material as a white solid used as is. LC (Method B): 1.747 min. 1H NMR (400 MHz, acetone) δ ppm 8.54 - 8.58 (m, 1H) 8.41 (dd, J=3.1, 0.8 Hz, 1H) 8.07 (ddd, J=10.3, 2.7, 1.7 Hz,1H) 8.03 (dd, J=9.0, 0.8 Hz,1H) 7.69 (ddd, J=9.0, 2.6, 1.4 Hz, 1H) 7.50 (dd, J=8.8, 2.9 Hz, 1H) 3.96 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sulfuric acid;Reflux; | To a 50 mL round-bottomed flask fitted with a reflux condenser and charged with <strong>[871329-84-9]3-carboxy-5-fluorophenylboronic acid</strong> (0.53 g, 2.88 mmol) in methanol (16 mL) was added a 6 M aqueous solution of sulfuric acid (0.33 mL, 1.98 mmol) and the mixture was heated to reflux overnight. The cooled mixture was diluted with water and the product was extracted with diethyl ether (x3). The combined organic extract was concentrated to give the title material (0.535 g, 94%) as white solid. LC (Method B): 1.596 min. LCMS (APCI): calcd for C8H7BF04 [M-H]- m/z 197.043, found 197.2. 1H NMR (400 MHz, acetone-d6): δ ppm 8.34 (s, 1 H) 7.80 (ddd, J= 9.2, 2.7, 1.0 Hz, 1H) 7.72 (ddd, J= 9.4, 2.7, 1.6 Hz, 1H) 7.56 (s, 2H) 3.91 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In acetonitrile; at 80.0℃; for 1.0h;Inert atmosphere; | 6-chloropyrido[3,2-d]pyrimidin-4-amine (500 mg, 2.8 mmol) 3-A in acetonitrile (5 mL) was treated with 3-borono-5-fluoro-benzoic acid (CAS 269404-73-6) (560 mg, 3 mL), PDCL2(DPPF) (202 mg, 0.28 mmol) and 1 M potassium carbonate solution (8 mL). The reaction vial was purged with nitrogen, and heated to 80 C. for 1 hour. LCMS showed 100% conversion to desired product. Yellow precipitate was collected and LCMS indicated it is pure product 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluorobenzoic acid 3. The filtrate was concentrate and purified by prep HPLC. LC/MS (ESI+): m/z 285 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In water; N,N-dimethyl-formamide; at 65.0℃; for 19.0h;Inert atmosphere; | Step 1 : 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5- l)-5-fluorobenzoic acid Chemical Formula: C22H13CIF2N2O4 Molecular Weight: 442.80 A mixture of 5-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine- 3-carboxamide (500 mg, 1.30 mmol), <strong>[871329-84-9]3-borono-5-fluorobenzoic acid</strong> (264 mg, 1.43 mmol), Pd(Ph3P)4 (151 mg, 0.130 mmol) and cesium carbonate (637 mg, 1.96 mmol) was degassed and diluted with a water (1.6 mL)/DMF (16 mL) mixture. The mixture was degassed and heated to 65 C under N2. The reaction was allowed to stir at 65 C for 16 h. LCMS showed starting material still remained. An additional 0.5 equiv of <strong>[871329-84-9]3-borono-5-fluorobenzoic acid</strong>, Pd(Ph3P)4, and cesium carbonate was added and the reaction was allowed to stir for 3 h. LCMS indicated starting material was consumed. The mixture was diluted with EtOAc and washed with 1M HC1 aq, and sat NaCl aq. The organic phase was dried over Na2S04, filtered and concentrated and then triturated with DCM to give the expected product 3-(6-chloro-2-(4-fluorophenyl)-3- (methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-5-fluorobenzoic acid (380 mg, 0.858 mmol, 66% yield) consistent by LCMS and NMR. LC-MS retention time: 2.74 min; m/z (MH+): 442. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u CI 8 2.0x30mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min , a gradient of 100% solvent A / 0% solvent B to 0% solvent A / 100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 5% MeOH / 95% H20 / 10 mM ammonium acetate and solvent B was 5% H20 / 95% MeOH / 10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400MHz, DMSO-d6) δ 13.51 (br. s., 1H), 8.58 - 8.53 (m, 1H), 8.26 (s, 1H), 8.09 - 8.04 (m, 2H), 7.94 (t, J=1.5 Hz, 1H), 7.81 - 7.71 (m, 2H), 7.46 - 7.40 (m, 2H), 2.83 (d, J=4.8 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 110.0℃;Inert atmosphere; | General procedure: 5-Bromo-3-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (1 equiv.), Ar1 boronic acidderivate (1 equiv.) and K2CO3 (3 equiv.) in a mixture of dioxane/water (3/1, 0.1 mol/L) were degazedwith argon. Then Pd(dppf)Cl2 (0.02 equiv.) was added and the mixture was stirred at 110C for 5 h.Ar2 boronic acid derivate (1 to 1.5 equiv.) and K2CO3 (3 equiv.) were added and the mixture wasdegazed with argon. Pd(dppf)Cl2 (0.02 equiv.) was added and the mixture was stirred at 110Covernight. The solvent was removed under reduced pressure; then the mixture was dissolved in EtOAcand washed with a saturated aqueous NaHCO3 solution. The combined organic layers were dried overNa2SO4 and evaporated. The crude product and Cs2CO3 (3 equiv.) in a mixture of THF/MeOH (1/1,0.05 mol/L) were stirred at room temperature overnight. The solvents were evaporated under reducedpressure; then the mixture was dissolved in EtOAc and washed with a saturated aqueous NaHCO3solution. The combined organic layers were dried over Na2SO4 and evaporated. and the crude productwas purified by flash reverse phase chromatography with eluents: H2O + 1%TFA and ACN + 1%TFA(80/20 to 0/100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); In 1,4-dioxane; water; at 80.0℃; for 2.0h;Inert atmosphere; | A mixture of (1-(4-bromophenyl)-6-azaspiro[2.5]octan-6-yl)((R)-tetrahydrofuran-2-yl)methanone (500 mg, 1.37 mmol), 3-(dihydroxyboranyl)-5-fluorobenzoic acid (379 mg, 2.06 mmol), potassium phosphate (583 mg, 2.75 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (97.2 mg, 0.14 mmol) in 1,4-dioxane (15.00 mL) and water (3.00 mL) was stirred for 2 h at 80 C under nitrogen atmosphere. The mixture was cooled to room temperature and was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with water (containing 0.1% FA) and ACN (35% to 65% over 7 min). The product was separated by Chiral HPLC with the following conditions: Column: CHIRALPAK IC, 2 × 25 cm, 5 µm; mobile phase: Hexanes (containing 0.1% Formic acid) and 2-Propanol (hold 50% 2-Propanol in 16 min); Detector: uv 254 nm to afford the first eluting peak as Compound 164 (129 mg, 33%) as a white solid and the second eluting peak as Compound 165 (116.7 mg, 31%) as a white solid. Compound 164: 1H NMR (400 MHz, DMSO-d6) δ (ppm): 13.42 (br, 1H), 8.03 (s, 1H), 7.86-7.79 (m, 1H), 7.72-7.59 (m, 3H), 7.37 (d, J = 8.0 Hz, 2H), 4.76-4.51 (m, 1H), 3.81-3.52 (m, 4H), 3.25-3.14 (m, 2H), 2.15-1.88 (m, 3H), 1.87-1.67 (m, 2H), 1.59-1.47 (m, 2H), 1.28-1.03 (m, 3H), 0.94-0.88 (m, 1H). LCMS (ES, m/z): 424[M+H]+. Compound 165: 1H NMR (400 MHz, DMSO-d6) δ (ppm):13.40 (br, 1H), 8.03 (s, 1H), 7.86-7.78 (m, 1H), 7.73-7.58 (m, 3H), 7.37 (d, J = 8.0 Hz, 2H), 4.75-4.51 (m, 1H), 3.80-3.55 (m, 4H), 3.27-3.10 (m, 2H), 2.14-1.90 (m, 3H), 1.87-1.69 (m, 2H), 1.63-1.47 (m, 2H), 1.25-1.06 (m, 3H), 0.93-0.88 (m, 1H). LCMS (ES, m/z): 424 [M+H]+. |
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