Structure of 452972-10-0
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CAS No. : | 452972-10-0 |
Formula : | C5H5BClNO2 |
M.W : | 157.36 |
SMILES Code : | OB(O)C1=C(Cl)C=CN=C1 |
MDL No. : | MFCD06801679 |
InChI Key : | IMEPMEDDZNANPY-UHFFFAOYSA-N |
Pubchem ID : | 12067059 |
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 potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 80℃; for 3h;Inert atmosphere; | Pd(PPh3)2Cl2 (10 mg, 5% w/w), <strong>[452972-10-0]4-chloropyridin-3-ylboronic acid</strong> (124 mg, 0.785 mmol) and K2 CO3 (287 mg in 1 mL water, 2.08 mmol) is added consecutively to a stirred solution of (4aR,4bS,6aS,9aS,9bR)-1,4a,6a-trimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-7-yl trifluoromethanesulfonate (200 mg, 0.462 mmol) in 1,4-dioxane (15 mL). The reaction is heated to 80 C. under N2 for 3 hours. The reaction is cooled to room temperature and partitioned between ethyl acetate (50 mL) and water (50 mL). The layers are separated and the aqueous layer extracted with ethyl acetate (25 mL×3). The combined organic layers are dried over Na2 SO4. After filtration, the organic phase is concentrated under vacuum and the residue is purified by prep-TLC (using PE/EA=1/1) to afford (4aR,4bS,6aS,9aS,9bS)-7-(4-chloropyridin-3-yl)-1,4a,6a-trimethyl-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinolin-2(3H)-one. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(triphenylphosphine)palladium(II) chloride; caesium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 18h; | General procedure: To a DMF (35.0 mL/1 mmol of substrate) solution of a 7d-II or 7a or 7b (1 equiv) was added to bis(triphenylphosphine)palladium dichloride (0.2 equiv), cesium carbonate (2 equiv) and boronic acids 8 (2 equiv) in water (9.0 mL/1 mmol of substrate) at 80 C. After being stirred at 80 C for 18 h, the reaction mixture was quenched by addition of water and the product was extracted with ether three times. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(triphenylphosphine)palladium(II) chloride; caesium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 18h; | General procedure: To a DMF (35.0 mL/1 mmol of substrate) solution of a 7d-II or 7a or 7b (1 equiv) was added to bis(triphenylphosphine)palladium dichloride (0.2 equiv), cesium carbonate (2 equiv) and boronic acids 8 (2 equiv) in water (9.0 mL/1 mmol of substrate) at 80 C. After being stirred at 80 C for 18 h, the reaction mixture was quenched by addition of water and the product was extracted with ether three times. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 36A N-alpha-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-(4-chloropyrimidin-3-yl)-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide trifluoroacetate (0540) (0541) 100 mg (0.16 mmol) of 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide and 18.4 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 1.5 ml of 1,2-dimethoxyethane and stirred at RT for 10 min. A solution of 92 mg (0.48 mmol) of <strong>[452972-10-0](4-chloropyridin-3-yl)boronic acid</strong> in 0.50 ml of ethanol was added dropwise to the reaction mixture. After the addition of 1.2 ml of 2N aqueous sodium carbonate solution, the mixture was stirred under reflux for 3 h. 1N aqueous hydrochloric acid was added to the reaction mixture, the salts were filtered off and the filtrate was separated by preparative HPLC (mobile phase: acetonitrile/water gradient, 0.1% trifluoroacetic acid). This gave 83 mg (65% of theory) of the title compound. (0542) LC-MS (Method 1): Rt=1.03 min; MS (ESIneg): m/z=657 [M-H-TFA]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 60℃; | General procedure: To a solu of 14 (60 mg, 0.14 mmol) in DMF (2 mL) was added selected aryl boronic acid (0.22 mmol) and 2 M Na2CO3 (0.2 mL). The reaction mixture was degassed with bubbling N2 (g) for 10 mins. Added PdCl2(dppf) (10 mg, 0.013 mmol), heated to 60 C and stirred for 10-30 mins. The reaction was cooled to room temperature, diluted with 5% LiCl (aq. Solu., 16 mL) and extracted with EtOAc (2 x 10 mL). The combined organic extracts were washed with 5% LiCl (aq. Solu., 2 x 15 mL) and brine (20 mL), dried over Na2SO4, passed through a plug of celite and concentrated under vacuum. The residue was purified by column chromatography using 0 to 100% EtOAc in hexanes then 0 to 10% MeOH in EtOAc to afford the desired product: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper (I) acetate; triethylamine; In dichloromethane; at 0℃; for 6h;Molecular sieve; Inert atmosphere; | The method is the same as the synthesis of intermediate M1, except the following reactionM1-2 50mmol, <strong>[452972-10-0]4-chloropyridine-3-boronic acid</strong> 100mmol,Copper acetate 50mmol,500 mmol of triethylamine, 10 g of 4A molecular sieve,500mL of dichloromethane was added to the reaction flask,Reaction at 0 for 6h under air atmosphere,After the reaction is completed, it is filtered and concentrated. The intermediate M4 separated by column chromatography |
A659430 [1072945-69-7]
(4-Chloropyridin-3-yl)boronic acid hydrochloride
Reason: Free-salt