Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 1009307-13-4 | MDL No. : | MFCD09027313 |
Formula : | C11H19BO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZXDDITJXZPTHFE-BQYQJAHWSA-N |
M.W : | 226.08 | Pubchem ID : | 23553751 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.73 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 62.74 |
TPSA : | 44.76 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) : | -6.31 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.93 |
Log Po/w (WLOGP) : | 1.74 |
Log Po/w (MLOGP) : | 0.64 |
Log Po/w (SILICOS-IT) : | 0.99 |
Consensus Log Po/w : | 1.06 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.19 |
Solubility : | 1.45 mg/ml ; 0.0064 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.49 |
Solubility : | 0.725 mg/ml ; 0.00321 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.06 |
Solubility : | 1.98 mg/ml ; 0.00875 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.41 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-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 |
---|---|---|
65% | With methanol; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane; copper(l) chloride; sodium t-butanolate In tetrahydrofuran at 20℃; for 24 h; Inert atmosphere | General procedure: CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and Xantphos ligand (8.7 mg, 0.015 mmol) were placed in an oven-dried Schlenk tube under nitrogen and THF (0.45 mL) were added. The reaction mixture was stirred for 30 min at room temperature and then bis(pinacolato)diboron (127 mg, 0.5 mmol) in THF (0.3 mL) was added. The reaction mixture was stirred for 10 min and α,β-acetylenic ester 2 (0.5 mmol) was added, followed by MeOH (40 μL, 1 mmol). The reaction tube was washed with further THF (0.2 mL), sealed, and stirred until no starting material was detected by TLC. The reaction mixture was filtered through a pad of Celite and concentrated. The product was purified by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With methanol; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; copper(l) chloride; sodium t-butanolate; In tetrahydrofuran; at 20℃; for 24h;Inert atmosphere; | General procedure: CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and Xantphos ligand (8.7 mg, 0.015 mmol) were placed in an oven-dried Schlenk tube under nitrogen and THF (0.45 mL) were added. The reaction mixture was stirred for 30 min at room temperature and then bis(pinacolato)diboron (127 mg, 0.5 mmol) in THF (0.3 mL) was added. The reaction mixture was stirred for 10 min and alpha,beta-acetylenic ester 2 (0.5 mmol) was added, followed by MeOH (40 muL, 1 mmol). The reaction tube was washed with further THF (0.2 mL), sealed, and stirred until no starting material was detected by TLC. The reaction mixture was filtered through a pad of Celite and concentrated. The product was purified by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 40h; | Example 30: 4-(2-[5-((E)-2-Ethoxycarbonyl-vinyl)-2-phenyl-thiazole-4-carboiiyl]- amino}-acetyl)-piperazine-l-carboxylic acid butyl esterTo a mixture of intermediate 27.1 (300 mg) in DME (3 mL) was added 2- ethoxycarbonylvinylboronic acid pinacol ester (133 mg) followed by [Pd(PPri3)4] (34 mg) and a solution of K2CO3 (81 mg) in H2O (1.5 mL). The flask was evacuated and backfilled with argon and the mixture was stirred at 900C for 40 h. To drive the reaction to completion the boronic ester (3x 1 eq) was added at different interval, as well as an additional portion of cat. (Ix 0.05 eq). The reaction mixture was allowed to cool to RT and was extracted with EtOAc (3x). The combined org. layers were dried over MgSO4 evaporated to dryness. Purification by CC (EtOAc/Hept 0: 1 to EtOAc/Hept 7:3) followed by preparative HPLC (I) gave 66 mg of the desired product. LC-MS: tR = 1.15 min; [M+H]+: 529.35. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; | Example 39: 4-((S)-2-[5-((E)-2-Carboxy-vinyl)-2-phenyl-thiazole-4-carbonyl]-amino}-3- hydroxy-propionyl)-piperazine-l-carboxylic acid butyl ester To a mixture of intermediate 37.2 (295 mg), ethoxycarbonylvinylboronic acid pinacol ester (148 mg) and [Pd(PPh3)4] (32 mg) was added aq. K2CO2 (2M, 0.38 mL) and DME (3 mL) and the reaction mixture stirred overnight at 900C. The mixture was evaporated to dryness and directly purified by CC (EtOAc/Hept 1 :1, then EtOAc, 1% HOAc) to give two fractions: The first eluting fraction gave after evaporation 196 mg of a yellow solid. This corresponded to the desired ethyl ester (Intermediate 39.1). A second eluting fraction was repurified by preparative TLC (CH2Cl2ZMeOH 9:1) to give 9 mg of the desired acid (Example 39). LC-MS: tR = 1.09 min; [M+H]+: 559.44 (ester). LC-MS: tR = 0.92 min; [M+H]+: 531.03 (acid). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 1.5h; | Example 19: 4-((S)-4-Carboxy-2-{ [5-((E)-2-carboxy-vinyl)-2-phenyl-thiazole-4-carbonyl]- amino}-butyryl)-piperazine-l-carboxylic acid butyl esterTo a mixture of Example 15 (152 mg) in dioxane (1.5 mL) was added 2- ethoxycarbonylvinylboronic acid pinacol ester (64 mg) followed by [Pd(PPri3)4] (32 mg) and a solution Of K2COs (50 mg) in H2O (1.0 mL) and the reaction mixture was stirred at 900C for 1.5 h. The crude mixture was evaporated and the residue taken up in EtOH (2 mL). LiOH (50 mg) in MeOHZH2O (7:3, 1 mL) was added and the reaction mixture stirred at RT for 1 h. The reaction mixture was acidified to pH 3 with IN HCl and extracted with CH2Cl2 (3x). The combined org. phase were evaporated to dryness and purified by CC (EtOAc, then CH2Cl2MeOH 9: 1) to give 91 mg of the desired product. LC-MS: tR = 0.98 min; [M+H]+: 573.29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; acetonitrile; at 100℃;Inert atmosphere; | Example 19Table 1Compound 19Synthesis of 3-(5-amino-2-(4-(2-(3,3-difluoro-3-phosphonopropoxy)ethoxy)-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoic acid (19)Step 1: (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3)To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (6-1) (1.0 equiv.) in acetonitrile (0.3 M) and EtOH (0.5 M) was added K2CO3 (2.0 equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (6-2) (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The reaction was flushed again with N2 and stirred at 100 C. overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1:1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3) as a white solid. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; acetonitrile; at 100℃;Inert atmosphere; | Step 1 : (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (3) To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (1) (l.Oequiv.) in acetonitrile (0.3M) and EtOH (0.5M) was added K2CO3 (2.0equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)acrylate (2) (1.2equiv.) and Pd(PPh3)4 (O.lequiv.)- The reaction was flushed again with N2 and stirred at 100C overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1: 1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert- butoxycarbonylamino)-4-chlorophenyl)acrylate (3) as a white solid. | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; hexane; acetonitrile; at 20 - 100℃;Inert atmosphere; | To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (6-1) (1.0 equiv.) in acetonitrile (0.3 M) and EtOH (0.5 M) was added K2CO3 (2.0 equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (6-2) (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The reaction was flushed again with N2 and stirred at 100 C. overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1:1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium carbonate;(bis(tricyclohexyl)phosphine)palladium(II) dichloride; In 1,4-dioxane; at 120℃; for 0.166667h;Inert atmosphere; Microwave irradiation; | N-Cyclopropyl-6-iodo-4-(trifluoromethyl)nicotinamide (125 mg, 0.34 mmol) and <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (93 mg, 0.41 mmol) were dissolved in 2 ml of 1,4-dioxane and admixed under argon with sodium carbonate (180 mg, 1.72 mmol) and bis(tricyclohexylphosphine)palladium(II) dichloride. The reaction mixture was heated in a microwave (CEM Discover) at 120 C. (80 W) for 10 min. Then the reaction mixture was filtered through kieselguhr, and the filtrate was taken up in ethyl acetate, washed with hydrochloric acid (1 M), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was taken up in 1.5 ml of ethanol, admixed with sodium hydroxide solution (1M) and stirred at room temperature overnight. Then the reaction mixture was added to ice-cold dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure.Yield: 72 mg (70% of theory).HPLC-MS: logP=1.26; mass (m/z): 301.1 (M+H)+; 1H NMR (CD3CN) 0.56-0.58 (m, 2H), 0.76-0.79 (m, 2H), 2.80-2.85 (m, 1H), 6.96 (d, 1H), 7.08 (br. s, 1H), 7.69 (d, 1H), 7.87 (s, 1H), 8.74 (s, 1H), 9.5 (br. s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 1h;Microwave irradiation; | 1 g of 3-fluoro-4-iodo-6-pyrid-3-yl-9-(toluene-4-sulfonyl)-9H-pyrrolo[2,3-b:5,4-c']dipyridine 18, 1.24 g of the boronate 20i, 212 mg of tetrakis(triphenylphosphine)palladium(0), 898 mg of caesium carbonate, 20 mL of dioxane and 5 mL of water are introduced into a microwave reactor of suitable size. The mixture is irradiated for 1 hour at 120 C. The reaction medium is poured into a mixture of ethyl acetate and water with vigorous stirring. After separation of the phases, the organic phase is dried over MgSO4, filtered and then concentrated under reduced pressure. The residue is dissolved in 10 mL of THF and 10 mL of methanol, and then 1.065 g of lithium hydroxide monohydrate dissolved in 5 mL of water are added. After stirring overnight, 100 mL of water are added and the pH is brought to 5 by addition of aqueous hydrochloric acid solution. The expected compound is recovered by filtration. 552 mg (80%) of (2E)-3-[3-fluoro-6-(pyrid-3-yl)-9H-pyrrolo[2,3-b:5,4-c']dipyrid-4-yl]prop-2-enoic acid 94 are obtained.UPLC-MS-DAD-ELSD (LS): Rt (min)=0.56; (M+H)(+): 335(+); (M-H)(-): 333(-). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With sodium carbonate;(bis(tricyclohexyl)phosphine)palladium(II) dichloride; In 1,4-dioxane; water; at 150℃; for 0.166667h;Inert atmosphere; Microwave irradiation; | In a 30 ml microwave vessel, 1.18 g (1 eq, 3.84 mmol) of 4-bromo-N-cyclopropyl-2-(trifluoromethyl)benzamide and 868 mg (1 eq, 3.84 mmol) of <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> were dissolved in 8 ml of 1,4-dioxane. To this were added 9 ml of Na2CO3 (2M in water) and 283 mg (0.1 eq, 0.38 mmol) of bis(tricyclohexylphosphine)-palladium(II) dichloride, and the reaction mixture was saturated with argon for 5 min. Then the reaction mixture was heated in the microwave (CEM Discover) at 150 C. (80 watts) for 10 min. Subsequently, the dioxane solution was decanted off, the residue was washed with 1,4-dioxane and the combined organic phases were concentrated under reduced pressure. The residue was dissolved in water and washed with a small amount of diethyl ether. Subsequently, the mixture was acidified to pH=3 with 1 M HCl, and the aqueous solution was extracted with ethyl acetate (EA). After drying the organic phase and concentrating, 412 mg (35%) of (2E,Z)-3-[4-(cyclopropylcarbamoyl)-3-(trifluoromethyl)phenyl]acrylic acid were obtained as a white solid.HPLC-MS: logP=1.34, mass (m/z): 300.03 (M+H)+.1H NMR (400 MHz, d3-CD3CN): delta=7.90 (s, 1H), 7.80 (d, 1H), 7.70 (d, 1H, J=16 Hz), 7.50 (d, 1H), 6.60 (s, 1H, br), 6.55 (d, 1H, J=16 Hz), 2.80 (m, 1H), 0.75 (m, 2H), 0.55 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With potassium carbonate;dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In tetrahydrofuran; water; for 7h;Reflux; Inert atmosphere; | Example 19 Preparation of 1-(4-chlorobenzyl)-6-(3-chloro-4-isopropoxyphenylamino)-4-hydroxycarbonylethyl-1,3,5-triazine-2(1H)-one [Show Image] [Show Image] A mixture of 4-chloro-1-(4-chlorobenzyl)-6-(3-fluoro-4-isopropoxyphenylamino)-1,3,5-triazine-2(1H)-one (0.15 g, 0.34 mmol), 1,1'-bis(di-t-butylphosphinoferrocene)palladium(II) dichloride (22.23 mg, 034 mmol), and THF (3 mL) was placed in a flask under nitrogen. To the mixture were added (E)-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)acrylate (063 g, 0.49 mmol) and 2mol/L potassium carbonate (0.682 mL, 1.364 mmol), and the resulting mixture was heated at reflux for 7 hours. Then, the mixture was poured into water (30 mL) and the resulting mixture was extracted with chloroform (30 mL). The extract was dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting residue was purified on a hight performance liquid chromatography (0.3% HCO2H H2O/MeCN 50-80%) to give 1-(4-chlorobenzyl)-6-(3-chloro-4-isopropoxyphenylamino)-ethoxycarbonylethenyl-1,3,5-triazine-2(1H)-one (05 g, yield: 30%) as pale orange oil. 1H-NMR (delta ppm TMS / DMSO-d6): 1.20-1.28 (9H, m), 4.17-4.22 (2H, m), 4.54 (1H, brs), 5.10 (2H, brs), 7.40 (8H, brs), 8.14 (1H, s), 9.77 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90℃; for 17h;Inert atmosphere; | To a stirred solution of te t-butyl-7-bromo-2,3- dihydrobenzo[/][1 ,4]oxazepine-4(5H)-carboxylate (480 mg, 1 .46 mmol) in dioxane (20 ml_) was added (E)-ethyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)acrylate (360 mg, 1 .61 mmol), aqueous Na2CO3 (1 .44 ml_, 2 M, 2.92 mmol) and Pd(dppf)CI2 (33 mg, 0.04 mmol). The mixture was degassed with nitrogen and then heated at 90C for 17 h. The reaction mixture was diluted with H2O and extracted into DCM. The organic layer was passed through a phase separator and concentrated. Purification by flash silica column chromatography (gradient elution /'-hex to 25% EtOAc in /-hex) gave the title compound as a yellow oil (267 mg, 57%). LCMS (ES+) 320 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | A stirred solution of 5-bromo-3-(trifluoromethyl)pyridine (1 .0 g, 4.42 mmol), (E)-ethyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate (1 .0 g, 4.43 mmol), Pd(PPh3) (51 1 mg, 0.44 mmol) and Na2CO3 (13.3 mL, 1 M solution, 13.3 mmol) was degassed with nitrogen for 10 min and then heated to 100C for 17 h. The mixture was allowed to cool, diluted with water (20 mL), and extracted into DCM (3 x 20 mL). The product was extracted from the organic layers with sat. NaHCO3 (20 mL). The pH was adjusted to 5.5 and the resulting white precipitate collected by vacuum filtration (431 mg, 45%). LCMS indicated that the corresponding carboxylic acid had formed. In a separate flask, thionyl chloride (0.19 mL, 1 .99 mmol) was added slowly to MeOH (5 mL) at -78C, and the acid (431 mg, 1 .99 mmol) was added. The mixture was refluxed for 1 .5 h, cooled to r.t. and concentrated. The residue was dissolved in sat. NaHCO3 (20 mL) and extracted into DCM (3 x 20 mL), and the combined organic layers passed through a phase separator and concentrated to give the title compound as a colourless oil (403 mg, 88%). LCMS (ES+) 232 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With caesium carbonate; tetrakis(triphenylphosphine)palladium (0); In 1,4-dioxane; water; at 105℃; for 0.75h;Sealed tube; Microwave irradiation; | Step 2: ethyl (2E)-3-{2-chloro-5-[(dimethylamino)methyl]phenyl}acrylate A mixture of 1-(3-bromo-4-chlorophenyl)-N,N-dimethylmethanamine (0.54 g, 2.16 mmol), tetrakis(triphenylphosphine)palladium(0) (0.25 g, 0.22 mmol), cesium carbonate (2.12 g, 6.49 mmol), and <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (0.59 g, 2.60 mmol) in 1,4-dioxane (12 mL) and water (2.8 mL) were sealed in a vial and subjected to microwave irradiation at 105 oC for 45 min. The reaction mixture was diluted with water and EtOAc. The organic solution was separated and washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give ethyl (2E)-3-{2-chloro-5-[(dimethylamino)methyl]phenyl}acrylate (0.21 g, 35%). LCMS (FA): m/z=268.1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran;Reflux; | [Example 26] Preparation of 2-(3-chloro-4-isopropoxyphenylamino)-3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl) pyrimidine-4(3H)-one (I-132) To a mixture of 5-bromo-3-(4-chlorobenzyl)-2-(methylthio)pyrimidine-4(3H)-one (1.00 g, 2.89 mmol) and THF (20 mL) were added <strong>[1009307-13-4](E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) acrylic acid ethyl ester</strong> (981 mg, 4.34 mmol), [1,1'-bis(di-t-butylphosphino)ferrocene]dichloropalladium(II) (189 mg, 0.289 mmol) and 2mol/L potassium carbonate solution (5.8 mL, 11.6 mmol), and the resulting mixture was heated at reflux for 4 hours. To the reaction mixture was added water, and the mixture was extracted with chloroform. The extract was washed by brine, dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was washed by ethyl acetate to give 3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl)-2-(methylthio)pyrimidine-4(3H)-one (250 mg, Yield: 24%) as yellow solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.24 (3H, t, J = 6.9 Hz), 2.56 (3H, s), 4.17 (2H, q, J = 6.9 Hz), 5.27 (2H, s), 7.03 (1H, d, J = 15.9 Hz), 7.28 (2H, d, J = 8.1 Hz), 7.41 (2H, d, J = 8.1 Hz), 7.50 (1H, d, J = 15.9 Hz), 8.38 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃;Inert atmosphere; | Example 219A (E)-ethyl 3-(3-chloro-1-methyl-6-oxo-1,6-dihydropyridazin-4-yl)acrylate [0992] Example 219A was prepared according to the procedure used for the preparation of Example 9A, substituting Example 18B for Example 1A, and substituting (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate for 2-fluoro-5-nitrophenylboronic acid, respectively, to provide the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
412 mg | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In toluene; at 100℃; for 120h; | Preparation Example 23 A mixture of 1 g of tert-butyl (2-bromobenzyl)carbamate, 1.12 g of <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong>, 16 mg of palladium acetate, 72 mg of dicyclohexyl(2',6'-dimethoxybiophenyl-2-yl)phosphine, 1.5 g of potassium phosphate, and 20 mL of toluene was stirred at 100 C. for 5 days. To the reaction mixture was added ether, followed by filtration through silica gel. The filtrate was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography to obtain 412 mg of ethyl (2E)-3-(2-[(tert-butoxycarbonyl)amino]methyl}phenyl)acrylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 2h; | Step 2 [0745] (E)-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-yl)acrylate (182mg,0.81mmol) was dissolved in DME (4mL) and ethanol (1.5mL). To the solution were added Compound 39 (292mg, 0.54mmol), PdCl2 (dppf) (21.9mg, 0.027mmol), and 2mol/L aqueous sodium carbonate (0.81mL, 1.61mmol), and the mixture was stirred for 2 hours at 80 C. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed by brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 75/25) to give Compound 40 (246mg, Yield 89%) as colorless oil. [0746] 1H-NMR (CDCl3) delta: 7.87-7.79 (3H, m), 7.67 (1H, d, J = 16.2 Hz), 7.05-6.97 (4H, m), 6.56 (1H, d, J = 16.2 Hz), 5.03-4.92 (1H, m), 4.98 (1H, td, J = 7.1, 3.0 Hz), 4.71-4.63 (1H, m), 4.32 (2H, q, J = 7.2 Hz), 4.07 (1H, dd, J = 11.3, 7.5 Hz), 3.83-3.72 (2H, m), 3.37 (1H, t, J = 9.8 Hz), 2.78-2.66 (1H, m), 1.43-1.34 (9H, m), 0.51 (3H, d, J = 6.9 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate; In N,N-dimethyl acetamide; water; at 130℃; for 2h; | First Step Synthesis of Compound (104) [1174] Compound (101) (200 mg, 0.371 mmol) was dissolved in DMA (2 mL), and ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (126 mg, 0.557 mmol), [1,1?-bis(di-tert-butylphosphino)ferrocene]palladium dichloride (48.4 mg, 0.074 mmol), and a 2 mol/L aqueous potassium carbonate solution (0.371 mL, 0.743 mmol) were added, and the mixture was sealed and stirred at 130 C. for 2 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane-ethyl acetate) to give compound (104) (143 mg, 69% yield). [1175] MS: m/z=580.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 1.5h;Inert atmosphere; | A mixture of (1R,3aS,5aR,5bR,7aR,11aR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate, prepared as described in WO2011153315, (50 mg, 0.074 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (66.8 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium (8.54 mg, 0.0074 mmol) and sodium carbonate (39 mg, 0.369 mmol) in DME (1 mL) and water (1 mL) was heated to 100 C. for 1.5 hours. The reaction mixture was cooled to rt, extracted with ethyl acetate (3*5 mL). The extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography with 80-100% ethyl acetate/hexanes gradient to provide the title compound (20 mg, 43%). LCMS: m/e 627.55 (M+H)+, 3.60 min (method 6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere; | Step 2. Ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylate A mixture of 2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane (22 g, 58 mmol) (from Step 1), <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (16 mL, 70 mmol), and potassium carbonate (24 g, 170 mmol) in 1,4-dioxane (230 mL) and water (110 mL) was degassed with nitrogen for 10 min. The reaction mixture was treated with [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (2.4 g, 2.9 mmol), degassed with nitrogen for another 10 min, and heated at 80 C. for 2 h. The reaction mixture was filtered through Celite and washed with ethyl acetate (300 mL). The filtrate was poured into water (400 mL). The aqueous layer was separated and extracted with additional ethyl acetate (300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude brown solid. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product (20 g, 96%). 1H NMR (400 MHz, CDCl3) delta 7.74 (d, J=16.5 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 6.70 (dd, J=16.5, 0.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 4.10-3.99 (m, 2H), 3.91 (q, J=7.0 Hz, 2H), 3.87-3.76 (m, 2H), 1.73 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.33 (t, J=7.1 Hz, 3H). LCMS for C17H21ClFO5 (M+H)+: m/z=359.1. Found: 359.1. |
96% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; at 80℃; for 2h;Inert atmosphere; | A mixture of 2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane (22 g, 58 mmol) (from Step 1), <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (16 mL, 70 mmol), and potassium carbonate (24 g, 170 mmol) in 1,4-dioxane (230 mL) and water (110 mL) was degassed with nitrogen for 10 min. The reaction mixture was treated with [1,1?-bis (diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (2.4 g, 2.9 mmol), degassed with nitrogen for another 10 min, and heated at 80 C. for 2 h. The reaction mixture was filtered through Celite and washed with ethyl acetate (300 mL). The filtrate was poured into water (400 mL). The aqueous layer was separated and extracted with additional ethyl acetate (300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude brown solid. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product (20 g, 96%). NMR (400 MHz, CDCl3) delta 7.74 (d, J=16.5 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 6.70 (dd, J=16.5, 0.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 4.10-3.99 (m, 2H), 3.91 (q, J=7.0 Hz, 2H), 3.87-3.76 (m, 2H), 1.73 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.33 (t, J=7.1 Hz, 3H). LCMS for C17H21CIFO5 (M+H)+: m/z=359.1; Found: 359.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
702 mg | With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 100℃; for 24h;Inert atmosphere; | A mixture of (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.81 g), Pd(PPh3)2Cl2 (551 mg), intermediate 224.1 (3.9 g) in DMF (70 mL) and 1M Na2CO3 (39.3 mL) was stirred at 100 C. under argon for 24 h. The reaction mixture was allowed to cool down, diluted with EA and washed with citric acid (10%), water and brine. The aq. layers were extracted with EA. The combined org. layers were dried over MgSO4, filtrated off and evaporated to dryness to afford 6.33 g of brown oil. CC (Biotage, SNAP 100 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 4CV, 5 to 15 over 4CV, 15 for 5CV; second CC: SNAP 50 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 5CV, 5 to 15 over 10CV, 15 for 5CV) afforded 702 mg of brown resin. LC-MS (B): tR=0.78 min; [M+H]+: 488.54. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; ethanol; at 90℃; for 6h;Inert atmosphere; | To a solution of (5) (109 mg, 0.302 mmol) in dioxane (1.0 ml) and EtOH (1.0 ml) were added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (82 mg, 0.363 mmol), PdCl2(PPh3)4 (12.7 mg, 0.018 mmol) and K3PO4 (64.2 mg, 0.302 mmol) at room temperature under nitrogen. Then the reaction mixture was heated to 90 C. After being stirred for 6 hrs at 90 C., the reaction mixture was quenched with H2O and extracted with ethyl acetate. The resulting organic layer was washed with H2O and brine, dried over Na2SO4 and concentrated in vacuo. The liquid residue was chromatographed on silica gel eluting with a gradient of hexane/ethyl acetate (5-15%) to afford 81.9 mg of the desired product (59a) in 64% as a yellow solid. (0864) 1H-NMR (DMSO-d6) delta: 9.14 (1H, s), 8.51 (1H, s), 7.98 (1H, d, J=16.17 Hz), 7.06 (1H, d, J=15.16 Hz), 4.99 (2H, s), 4.25 (2H, q, J=7.07 Hz), 1.28 (3H, t, J=7.07 Hz), 0.89 (9H, s), 0.14 (6H, s). LC/MS (M+1): 424. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With dichloro[1,1?-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P?]palladium; potassium carbonate; In tetrahydrofuran; for 4h;Reflux; | EXAMPLE 24 Preparation of 2-(3-chloro-4-isopropoxyphenylamino)-3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl) pyrimidine-4(3H)-one (I-132) To a mixture of 5-bromo-3-(4-chlorobenzyl)-2-(methylthio)pyrimidine-4(3H)-one (1.00 g, 2.89 mmol) and THF (20 mL) were added <strong>[1009307-13-4](E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) acrylic acid ethyl ester</strong> (981 mg, 4.34 mmol), [1,1'-bis(di-t-butylphosphino)ferrocene]dichloropalladium(II) (189 mg, 0.289 mmol) and 2 mol/L potassium carbonate solution (5.8 mL, 11.6 mmol), and the resulting mixture was heated at reflux for 4 hours. To the reaction mixture was added water, and the mixture was extracted with chloroform. The extract was washed by brine, dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was washed by ethyl acetate to give 3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl)-2-(methylthio)pyrimidine-4(3H)-one (250 mg, Yield: 24%) as yellow solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.24 (3H, t, J=6.9 Hz), 2.56 (3H, s), 4.17 (2H, q, J=6.0 Hz), 5.27 (2H, s), 7.03 (1H, d, J=15.9 Hz), 7.28 (2H, d, J=8.1 Hz), 7.41 (2H, d, J=8.1 Hz), 7.50 (1H, d, J=15.9 Hz), 8.38 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In water; butan-1-ol; at 100℃;Inert atmosphere; | Step 3: Preparation of (E)-ethyl 3-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-dlpyrimidin-5- yl)methyl)-4-methoxyphenyl)acrylate5-(5-Bromo-2-methoxybenzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine (from the previous step, 1 equiv.), <strong>[1009307-13-4](E)-ethyl 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate</strong> (1 .5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv.), 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl (Sphos, 0.2 equiv.) and K3P04 (2 equiv.) were dissolved in 4:1 n- butanohwater (0.1 M). After degassing with N2, the vessel was sealed and heated at 100 C O/N. After cooling down to room temperature, the reaction mixture was quenched with equal volume of saturated sodium bicarbonate aqueous solution, and was extracted with DCM. The organic layers were combined and dried over anhydrous sodium sulfate, and concentrated in vacuuo. The crude was purified by reverse phase prep-HPLC to afford title compound as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.0 mg | The compound obtained in Example 1b (100 mg), 2-(ethoxycarbonyl)vinyl boronic acid pinacol ester (67.8 mg), 1,2-dimethoxyethane (2mL), aqueous solution of sodium carbonate (63.6 mg) (1 mL) was added, and the mixture was stirred at room temperature for 5 minutes. [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethanecomplex (16.3 mg) was added at a microwave reactor and allowed to react for 15 minutes at 130 C. The reaction mixture was cooled to room temperature and extracted with water was added ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (92.5 mg) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16.66% | With tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 140℃; for 12h; | A mixture of 6-chloro-3-methyl-3H-[1 ,2,3]triazolo[4,5-c]pyridine (3.000 g, 17.80 mmol), (E)-ethyl3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate (9.90 mL, 89 mmol), TEA (12.40 mL, 89mmol), tetrakis(triphenylphosphine)palladium(0) (1 .453 g, 1 .780 mmol) in N,Ndimethylformamide (50 mL) was stirred at 140 C for 12 h. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to afford the title compound (E)-ethyl 3-(3-methyl-3H-[1 ,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate (71 0 mg,2.97 mmcl, 16.66 % yield). LC-MS m/z 233.0 (M+H), 1 .51 mm (ret. time). |
710 mg | With tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 140℃; for 12h; | A mixture of 6-chloro-3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridine (3.000 g, 17.80 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (9.90 mL, 89 mmol), TEA (12.40 mL, 89 mmol), tetrakis(triphenylphosphine)palladium(0) (1.453 g, 1.780 mmol) in N,N- dimethylformamide (50 mL) was stirred at 140C for 12 h. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to afford the title compound (E)-ethyl 3-(3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate (710 mg, 2.97 mmol, 16.66 % yield). LC-MS m/z 233.0 (M+H)+, 1.51 min (ret. time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere; | To a mixture of ethyl 24-amino-25-iodo-4-oxo-3-aza- 1 (4,2)-pyridina-2( 1 ,2)-benzenacyclononaphane-9-carboxylate (60 mg, 0.125 mmol) in DMF(1.0 mL) was added K2C03 (17.30 mg, 0.125 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)acrylate (28.3 mg, 0.125 mmol), PdC12(dppf) (92 mg, 0.125 mmol). Themixture was then stirred at 80C for 12 h under N2. The reaction mixture was concentrated and the residue was purified by prep-TLC (5i02, DCM:MeOH=8: 1) to give the title compound. LC/MS (ESI) m/z 452.2(M+i). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In tetrahydrofuran; water; at 130℃; for 0.5h;Microwave irradiation; | Step 4 (0694) Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)acrylate (125mg, 0.554mmol), PdCl2 (dppf) CH2Cl2 (22.6mg, 0.028mmol) and 2 mol/L sodium carbonate aqueous solution (0.554mL, 1.11mmol) were added into THF (5.6mL) solution of Compound 47 (271mg, 0.268mmol), and the mixture was stirred at 130C by using a microwave device for 30 minutes. After brine was added into the reaction mixture, the mixture was extracted with chloroform. After the organic layer was dried with magnesium sulfate anhydrous, the solvent was removed in vacuo. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to give Compound 48 (244mg, 88%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere; | To a solution of 4,6-dichloro-5-(2-methoxybenzyl)pyrimidin-2-amine (1.0 eq) in 3:1 dioxane/H2O (0.14M) was added ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.2 eq), K2CO3 (2.0 eq), and Pd(dppf)Cl2 (0.1 eq). The mixture was stirred at 100 C. for 3 h under nitrogen. The reaction was diluted with water, and the aqueous phase was extracted with EA. Combined organic layers were washed with water, then brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (PE/EA=40:3) to give the title compound as light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | To a solution of 4,6-dichloropyrimidin-2-amine (1.0 eq) in 3:1 dioxane/H2O (0.3M) was added ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.1 eq), K2CO3 (2.0 eq), and Pd(dppf)Cl2 (0.1 eq). The mixture was stirred at 100 C. for 2 h under nitrogen. The reaction was diluted with water, and the aqueous layer was extracted with EA. The combined organic layers were washed with water, brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (PE/EA=10:1) to give the title compound as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.1 g | With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tetrahydrofuran; water; at 80℃; for 16h; | A mixture of 3-amino-4-bromopyridine (5.0 g, 28.9 mmol), (E)-ethyl 3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl) acrylate (7.84 g, 34.7 mmol), Pd(OAc)2 (250 mg), Xantphos (400 mg) and K2CO3 (5.18 g, 37.6 mmol) in THF (150 mL) and H20 (30 mL) was stirred at 80 C for 16 hrs. The resulting mixture was filtered. The filtrate was diluted with EA (100 mL), washed with brine (100 mL), then dried over Na2S04 and concentrated in vacuo. The residue was purified by column (PE:EA=10: 1 to DCM: MeOH = 50: 1, v:v) to give ethyl (E)-3- (3-amino-4-pyridyl)prop-2-enoate (3.1 g) as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃;Sealed tube; | To a degassed solution of 5-bromo-2-methoxypyridine (2 g, 10.64 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (2.405 g, 10.64 mmol) and K2CO3 (4.41 g, 31.9 mmol) in 1,4-dioxane (30 mL) and water (10 mL) was added Pd(PPh3)4 (0.492 g, 0.425 mmol). The reaction mixture was stirred in a seal vial at 100 C overnight. After cooled to rt, the mixture was diluted with water (15 mL), and extracted with CH2Cl2 (3 x 10 mL), the combine organics were dried (Na2SO4), filtered, and concentrated. the residue was purified via flash chromatography (80 g silica gel, 0 to 100% hexane/ethyl acetate ) to afford Intermediate 1A (662 mg, 3.19 mmol, 30% yield) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium phosphate; ethanol; 2C2H3O2(1-)*C12H8N2*(x)H2O*Ni(2+); In 1,4-dioxane; at 60℃; for 24h;Schlenk technique; Sealed tube; Inert atmosphere; | General procedure: To an oven-dried, 10 mL round-bottomed flask equipped with a stir bar was added PhenNi(OAc)2·xH2O (20 mg, 0.050 mmol, 5 mol%), pyridinium salt (1.0 mmol, 1.0 equiv), vinylboronic acid pinacol ester (2.0 mmol, 2.0 equiv), and K3PO4 (531 mg, 2.5 mmol, 2.5 equiv). The flask was fitted with a rubber septum, sealed with parafilm, and thenpurged with N2 for 20 min. Dioxane (2.0 mL) was added, followed by EtOH (0.29 mL, 5.0 mmol, 5.0 equiv). The mixture was stirred at 60 C for 24 h. The mixture was allowed to cool to room temperature, and then filtered through a small pad of Celite. The filter cake was washed with CH2Cl2 (4 × 25 mL), and the filtrate was concentrated. The cross-coupled product was then purified via silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 0.5h;Microwave irradiation; | C-3a (400 mg; 1.41 mmol) and Cs2C03 (1 .41 g; 4.24 mmol) are suspended in DME (7.5 mL) and water (2.5 mL). Argon is purged through the mixture and ethyl (2E)-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)prop-2-enoate (SM-6d) (383 mg; 1 .70 mmol) and Pd(dppf)CI2-DCM (1 18 mg; 0.14 mmol) are added, the vial is sealed and heated to 100 C under microwave irradiation for 30 min. After cooling to rt EtOAc and water are added and the layers are separated. The aqueous layer is extracted with EtOAc. The combined organic layer is washed with water and brine, dried over MgS04, filtered and evaporated. The residue is triturated with MeOH, the solid is collected by filtration and dried in vacuo to give ethyl (2E)-3-(1 -methyl-6-nitro-2-oxo-1 ,2- dihydroquinolin-3-yl)prop-2-enoate (IM-1 q) (HPLC-MS: tRet. = 1 .14 min; MS (M+H)+ = 303; method 1 ). |
Tags: 1009307-13-4 synthesis path| 1009307-13-4 SDS| 1009307-13-4 COA| 1009307-13-4 purity| 1009307-13-4 application| 1009307-13-4 NMR| 1009307-13-4 COA| 1009307-13-4 structure
[ 581802-26-8 ]
(E)-2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol
Similarity: 0.71
[ 126689-00-7 ]
4,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane
Similarity: 0.70
[ 154820-99-2 ]
2-(3,3-Dimethylbut-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 0.67
[ 212127-80-5 ]
2-(2,5-Dihydrofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 0.66
[ 269409-99-6 ]
Ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
Similarity: 0.65
[ 581802-26-8 ]
(E)-2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol
Similarity: 0.71
[ 126689-00-7 ]
4,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane
Similarity: 0.70
[ 154820-99-2 ]
2-(3,3-Dimethylbut-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
Similarity: 0.67
[ 126726-62-3 ]
4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane
Similarity: 0.61
[ 1049004-32-1 ]
Ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate
Similarity: 0.61
[ 269409-99-6 ]
Ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
Similarity: 0.65
[ 195062-62-5 ]
Ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
Similarity: 0.65
[ 850568-72-8 ]
tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
Similarity: 0.64
[ 480424-70-2 ]
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl acetate
Similarity: 0.64
[ 903895-48-7 ]
tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
Similarity: 0.63
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
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. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
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. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
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: |
P370 + P380 | In case of fire: Evacuate area. |
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 |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
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 |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
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 |
H270 | May cause or intensify fire; oxidizer |
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 |
H304 | May be fatal if swallowed and enters airways |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :