Structure of 1048330-10-4
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CAS No. : | 1048330-10-4 |
Formula : | C9H11BO4 |
M.W : | 193.99 |
SMILES Code : | CC1=CC=C(B(O)O)C=C1C(OC)=O |
MDL No. : | MFCD13191800 |
InChI Key : | CDWTTYCJDYKRNE-UHFFFAOYSA-N |
Pubchem ID : | 54758887 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.51 |
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 | 1.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -0.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -0.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.13 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.82 |
Solubility | 2.96 mg/ml ; 0.0152 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.03 |
Solubility | 1.8 mg/ml ; 0.00928 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -1.75 |
Solubility | 3.41 mg/ml ; 0.0176 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 | -6.74 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 | 1.0 |
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) | 2.02 |
* 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 tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 65.0℃; for 1.0h;Inert atmosphere; | General procedure: To a solution of Intermidiate-1 (1 g, 1.781 mmol), methyl 3-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)benzoate (0.467 g, 1.781 mmol) and sodium carbonate (0.321 g, 5.34 mmol) in ethanol (5 mL), toluene (5 mL) and water (2 mL) bubbled the nitrogen for 30 minutes. Tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.089 mmol) was added to the reaction mixture and again nitrogen was bubbled for 10 minutes. The reaction mixture was then heated to 65 °C and further maintained for lh. Reaction was monitored by TLC. The resulting solid was removed by filtration through celite bed. The filtrate was extracted with ethyl acetate (2 x 25 mL) and washed with water (15 mL) and brine solution (15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude compound. This crude compound was further purified by flash chromatography (Biotage) (ethyl acetate: hexane=l :20) to give title compound (660 mg, 67.7percent) m/z 548.57. The title compound was prepared by following the similar procedure as described Step-i to Step-3 of Example-i in sequential manner by taking Intermediate-3 and (3- (methoxycarbonyl)-4-methylphenyl)boronic acid.The two diastereomers were separated by chiral preparative HPLC [CHIRAL PAK ID, 250mm x 4.6,5ji; A=n-hexane IPA (90/10 percentv/v, 0.1 percentDEA), B=IPA; A:B=90/10 percentv/v;Flow = 1.0 mllmin] Isomer ?a?: tR = 6.05, Isomer ?b?: tR = 6.62; m/z, 461.9. (tR is retention time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80.0℃;Inert atmosphere; | Step-i: (R)-Methyl 4-methyl-3 -(methylcarbamoyl)-5 -(2-(( 1 -(naphthalen- l-yl) ethyl) amino) ethoxy)- [1,1 -biphenyl] -3-carboxylateTo a solution of (R)-3-Bromo-N-methyl-5-(2-((1-(naphthalen-1-yl) ethyl) amino) ethoxy) 10 benzamide (Intermediate-3a) (1 equivalent) in dioxane was added, (3-(methoxy carbonyl)-4-methyiphenyl) boronic acid (1.2 equivalent), Na2CO3 (2 equivalent) and water. The mixture was degassed for 15 mm and then, PdC12 (dppf) (5mol percent) was added. The reaction mixture was heated to 80°C overnight. TLC showed complete conversion of starting material so it was filtered through a pad of celite and concentrated to give the crude product that waspurified by column chromatography (10percent Ethyl acetate-Hexanes) to give the desired compound (50-60 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 90.0℃; for 4.0h;Inert atmosphere; | To an oven-dried round-bottomed flask was added Intermediate-2 (100 mg, 0.329 mmol), [3- (methoxycarbonyl)-4-methylphenyl] boronic acid (63.8 mg, 0.329 mmol) in anhydrous dioxane (10 ml) under N2 atmosphere. A degassed aqueous solution of sodium carbonate (105 mg, 0.986 mmol) was then added via syringe to the vigorously stined reaction mixture, followed by tetrakis(triphenylphosphine)palladium (0) (18.99 mg, 0.0 16 mmol). The reaction mixture was stirred at 90°C for 4 h. TLC showed completion of reaction. The reaction mixture was diluted with water (25 ml) and ethyl acetate (25 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (2 x 15 ml). The combined organic extract was washed with water (2 x 25 ml), brine (50 ml) and dried over anhydrous sodium sulphate, filtered and concentrated in vacuo to get 0.2g of the crude residue. The crude compound was purified by column chromatography over silica gel (100-200 mesh) with isocratic elution of 20 percent ethyl acetate in hexane to afford title compound ( mg, 65percent) as a off white solid. ?H NMR (400 MHz, CDC13-d6) oe 10.22 (s, 1H), 8.39 (s, 1H), 8.11-8.07 (m, 2H), 7.93-7.90 (m, 2H), 7.64-7.62 (m, 2H), 7.56-7.54 (m, 1H), 7.42 (d, J =7.6 Hz, 1H), 3.91 (s, 3H), 2.72 (s, 3H); MS (ES+) mlz = 304.54. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 140.0℃; for 1.0h;Inert atmosphere; | Example 60A Methyl 4'-[(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-oxo-3-[4-(2H-tetrazol-5-yl)phenyl]amino}propyl]-4-methylbiphenyl-3-carboxylate Under argon, 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl) carbonyl]-N-[4-(2H-tetrazol-5-yl)phenyl]-L-phenylalaninamide (1.00 g, 1.60 mmol) from Example 6A, <strong>[1048330-10-4][3-(methoxycarbonyl)-4-methylphenyl]boronic acid</strong> (433 mg, 2.23 mmol) and sodium carbonate (507 mg, 4.79 mmol) were initially charged in 12 ml of DMF/water (10:2). Subsequently, 1, 1-bis(diphenylphosphino)ferrocenedichloropalladium(II) (117 mg, 0.16 mmol) was added and the mixture was stirred at 140° C. in a microwave for 1 h. At RT, the reaction mixture was then diluted with 50 ml of water, acidified with 1M hydrochloric acid and extracted twice with 70 ml each time of ethyl acetate. The combined organic phases were washed once each with water and saturated aqueous sodium chloride solution, dried over sodium sulphate and filtered, and the filtrate was concentrated. The residue obtained was taken up in ethyl acetate, and the precipitate formed was filtered off, washed with ethyl acetate and dried under high vacuum. The crude product obtained in this manner (82percent pure) was reacted further without further purification. LC-MS (Method 1): Rt=1.14 min; MS (ESIpos): m/z=696 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In tetrahydrofuran; water; at 100.0℃; for 6.0h;Inert atmosphere; Sealed tube; | Combined <strong>[1048330-10-4](3-(methoxycarbonyl)-4-methylphenyl)boronic acid</strong> (416 mg, 2.145 mmol), 2-chloro-3- (l-((l-fluorocyclopentyl)methyl)-lH-pyrazol-4-yl)pyridine (INTERMEDIATE F3, 400 mg, 1.430 mmol), and di-tert-butylphoshinoferrocene palladium dichloride (100 mg, 0.154 mmol) in a large reaction vial. Sealed the vial and inerted the atmosphere with nitrogen. Added THF (14.3 mL), and 1M aqueous tripotassium phosphate (4.3 mL, 4.3 mmol). The reaction was heated to 100°C for 6 hours. Cooled and partitioned the organic from the aqueous. Washed the organic with water (2 x 10 mL). Dried the organic over sodium sulfate, filtered and evaporated the filtrate. Purified by silica gel chromatography, eluting with 0-100percent Hex/EtOAc to give the title compound. MS(M+1): 394. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro[1,1?-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P?]palladium; In tetrahydrofuran; at 50.0℃; for 0.5h;Inert atmosphere; | To a 250-mL round bottom flask was added 2-chloro-3-(1-isopentyl-1H-pyrazol-4-yl)pyridine (5.0 g, 20.02 mmol), <strong>[1048330-10-4](3-(methoxycarbonyl)-4-methylphenyl)boronic acid</strong> (7.77 g, 40.0 mmol), and 1,1?- bis(di-tert-butylphosphino)ferrocene palladium dichloride (100 mg, 0.153 mmol). To the flask was added THF (100.0 mL) and 1 M potassium phosphate (60.1 mL, 60.1 mmol). A reflux condensorwas added and the reaction was purged with nitrogen and heated to 50C for 30 minutes. The reaction was cooled and the organic layer separated. The aqueous layer was extracted with with 2 x 10 mL ethyl aceteate, and the organic layers combined and dried over sodium sulfate. The sample was filtered, concentrated under reduced pressure, and purified by flash chromatography (0-60% ethyl acetate in hexanes) to yield the title compound. |
Tags: 1048330-10-4 synthesis path| 1048330-10-4 SDS| 1048330-10-4 COA| 1048330-10-4 purity| 1048330-10-4 application| 1048330-10-4 NMR| 1048330-10-4 COA| 1048330-10-4 structure
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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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