Structure of 40263-57-8
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 40263-57-8 |
Formula : | C5H4INO |
M.W : | 221.00 |
SMILES Code : | C1=CC=NC(=C1O)I |
MDL No. : | MFCD00023421 |
InChI Key : | HJBGMPCMSWJZNH-UHFFFAOYSA-N |
Pubchem ID : | 97179 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.93 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.51 |
Solubility | 0.685 mg/ml ; 0.0031 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.47 |
Solubility | 7.47 mg/ml ; 0.0338 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.41 |
Solubility | 0.866 mg/ml ; 0.00392 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 |
Yes |
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 |
-6.81 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 |
0.0 |
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 |
2.0 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) |
2.08 |
* 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 |
---|---|---|
82% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 70℃; for 14h;Inert atmosphere; | A mixture of <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (1 g, 4.5 mmol, 1.0 eq), 3,3-diethoxyprop-1-yne (754.0 mg, 5.9 mmol,1.3 eq), TEA (4.1 g, 41 mmol, 9.0 eq), CuT (172 mg, 905 imol, 0.2 eq) and Pd(PPh3)2C12 (318mg, 453 imol, 0.1 eq) in 10 mL of THF was degassed and purged with N2 three times. The mixture was stirred at 70 C for 14 hours under N2 atmosphere. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (Si02, eluting with petroleum ether: ethyl acetate = 100:1 to 2:1) to afford 820 mg of 2-(diethoxymethyl)furo[3,2- bjpyridine (3.7 mmol, 82% yield) as yellow oil. |
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; for 17h; | 2-Iodo-3-pyridinol (24 mmol), triethylamine (1.0 eq), 3,3-diethoxy-1-propyne (1.0 eq), bis(triphenylphosphine)palladium (II) chloride (0.02 eq), and copper(I) iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2*50 mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 1.28 (t, J=7.1 Hz, 6H), 3.70 (q, J=7.1 Hz, 4H), 5.68 (s, 1H), 7.05 (s, 1H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) m/z 222 (M+H)+. | |
With copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; for 17h; | [2-IODO-3-PYRIDINOL] (24 mmol), triethylamine (1.0 [EQ),] 3, [3-DIETHOXY-1-PROPYNE] (1.0 eq), bis (triphenylphosphine) palladium [(II)] chloride (0.02 [EQ),] and copper [(I)] iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2x50mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further [PURIFICATION.'H] NMR [(CDC13,] [400MHZ)] [5] 1.28 (t, J=7. [1HZ,] 6H), 3.70 (q, J=7. [1HZ,] 4H), 5.68 (s, 1H), 7.05 (s, [1H),] 7.23 (dd, J=8.5, 4.8Hz, [1H),] 7.77 (d, J=8. 5Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) [M/Z] 222 (M+H) [+.] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6 g | To a stirred solution of <strong>[40263-57-8]3-hydroxy-2-iodopyridine</strong> (10 g, 45.24 mmol) in THF : DMF (10 mL: 20 mL) at 0 C was added tert-BuO-K (6 g, 54.3 mmol) portion wise. After stirring the reaction mixture for 30 mi methoxymethyl chloride (4 mL, 50 mmol) was added at 0 C and the resulting mixture was allowed to stir at room temperature for 3 hrs. Reaction mixture was diluted with brine and extracted with EtOAc (3 x 150 mL). EtOAc part was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford crude mass which was purified by column chromatography using silica (100-200 mesh) and EtOAc-hexane as eluent to afford 2-iodo-3- (methoxymethoxy)pyridine (6.0 g) as off white solid. | |
9.9 g | To a solution of <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (CAS No. 40263-57-8) (9.67 g, 43.8 mmol, 1 equivalent) in THF (200 mL) was added sodium hydride (60% oil dispersion, 1.93 g, 48.1 mmol, 1.1 equivalents) at 0 C., and the reaction mixture was stirred at 0 C. for 10 minutes. To the solution was added chloromethyl methyl ether (3.66 mL, 48.1 mmol, 1.1 equivalents), and the mixture was stirred at 0 C. for 10 minutes and at room temperature for 1 hour. To the reaction mixture was added water, and then the mixture was concentrated under reduced pressure. The residue was extracted with chloroform, and the organic layer was concentrated under reduced pressure. The residue was purified with silica gel column chromatography (NH silica gel, 0%-40% ethyl acetate/n-heptane) to afford the title compound (9.9 g). 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.52 (s, 3H), 5.27 (s, 2H), 7.18 (dd, J=8.2, 4.5 Hz, 1H), 7.28 (dd, J=8.2, 1.6 Hz, 1H), 8.06 (dd, J=4.5, 1.6 Hz, 1H). MS [M+H]+=266 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper(l) iodide; L-proline; sodium hydroxide; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere; Sealed tube; | General procedure: A sealable reaction tube equipped with a magnetic stirrer bar was charged with 2-iodophenols 1 (1 mmol), alkynes 2 (1 mmol), NaOH (2 mmol), CuI (0.1 mmol), proline (0.3 mmol) and DMSO (5 mL), and the reaction vessel placed in an oil bath at 80 C under N2 . After stirring the mixture at this temperature for 12 h, it was cooled to room temperature and diluted with ethyl acetate, washed with water and brine, dried over by MgSO4. After the solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel to afford the corresponding product. |
79% | With potassium phosphate; In N,N-dimethyl-formamide; at 160℃;Schlenk technique; Inert atmosphere; Glovebox; Green chemistry; | General procedure: General produce: o-iodophenol (0.5 mmol), alkyne (1.0 mmol) andbase (1.0 mmol) were added into a 10 mL dry Schlenk tube under Ar,then anhydrous DMF (5 mL) was injected into the mixture using syringe.Then the solution stirred at preheated oil bath (160 C). The reactionwas monitored by TLC and GC.The mixture was cooled down toroom temperature after full conversion, then diluted with dichloromethaneand washed with water three times. The organic layerwas separated and washed with brine followed by drying with anhydrousNa2SO4. The filtrate was concentrated in vacuo to afford thecrude product, which was purified by flash column chromatography onsilica gel (petroleum ether). |
63% | With potassium phosphate; C43H36N4O4Pd; In dimethylsulfoxide-d6; at 120℃; for 10h; | General procedure: In a typical run, performed in air, a 25 mL of round bottom askwas charged with a mixture of 2-iodophenol (0.50 mmol), terminalalkyne (0.60 mmol), and K3PO4 (1.00 mmol). A palladium complex(2a or 2b, 0.0005 mmol) was added to the mixture, followed byDMSO (ca. 2 mL) as a solvent, and then the reaction mixture washeated (either at 90C or at 120C) for 10 h. The reaction mixturewas cooled to room temperature, and water (ca. 20 mL) was added.The resulting mixture was extracted with EtOAc (ca. 50 mL). Theorganic layer was further extracted with EtOAc (ca. 2 20 mL). Theorganic layers were combined and vacuum dried to obtain a crudeproduct that was subsequently puried by column chromatog-raphy. The obtained benzofuran derivatives (3aa3ap) were char-acterized by NMR and Mass spectroscopy (See SupportingInformation Figures S4-S23). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In toluene; at 90℃; for 5h; | 6-Ethynyl-3-[4-((l S,3R,5R)-8-methyl-8-azabicyclo[3.2.1]oct-3-yloxy)phenyl]-3H-thieno[3,2- d]pyrimidin-4-one (39.2 mg), bis(triphenylphosphine)palladium chloride (3.5 mg) and copper iodide (0.95 mg) were added to a solution of 2-iodo-3-pyridinol (22.1 mg) and triethylamine (0.272 mL) in toluene (1.36 mL). The reaction mixture was heated at 900C for 5 hours. The solvent was then removed in vacuo, the residue was taken up in ethyl acetate and water, and the organic phase was acidified with 2N hydrochloric acid. The organic phase was then washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 484.58 (C27H24N4O3S) was obtained in this way; MS (ESI): 485 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 70℃; for 16h;Under nitrogen; | Intermediate 11 Ethyl ?-^-furotS^-blpyridin^-yOpheny^-Z-I^frans-?methylcyclohexylJcarbonylKI- methylethyl)amino]-3-furancarboxylateTo Intermediate 10 (78 mg) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (40.8 mg), bis(triphenylphosphine)palladium dichloride (13 mg), copper (I) iodide (3.5 mg) and triethylamine (1.2 mL). The reaction was stirred at 7O0C, under nitrogen, for 16 h. The reaction was cooled, partitioned between saturated sodium bicarbonate solution and DCM1, passed through a hydrophobic and then concentrated. The crude product was dissolved in DCM, filtered and purified by ISCO companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane (0% to 100%) to give the title compound. MS calcd for (C3IH34N2O5 + H)+: 515 MS found (electrospray): (M+H)+ = 515 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 70℃; for 17h; | Intermediate 33Ethyl 5-(4-furo[3,2-b]pyridin-2-ylphenyl)-2-[[(fra?s-4- methylcyclohexyl)carbonyl](tetrahydro-3-furanyl)amino]-3-furancarboxylateA mixture of Intermediate 32 (228 mg), <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (112 mg), copper(l) iodide (10 mg), dichlorobis(triphenylphosphine)palladiurr) (II) (36 mg) and triethylamine (3.5 ml_) were stirred and heated in a Reacti-vial at 700C for 17 h. The reaction was cooled, partitioned between saturated sodium bicarbonate solution and DCM, separated using a hydrophobic frit and the organics were evaporated in vacuo. The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 0-100% EtOAc in cyclohexane to give the title compound. MS calcd for (C32H34N2O6 + H)+: 543 MS found (electrospray): (M+H)+ = 543 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 70℃; | Intermediate 37Ethyl 5-(4-furo[3,2-b]pyridin-2-ylphenyl)-2-[(frans-4-methylcyclohexyl)carbonyl][2- (methyloxy)ethyl]amino}-3-furancarboxylateA mixture of Intermediate 36 (220 mg), 2-?odo-3-hydroxypy?d?ne (1 12 mg), copper(l) iodide (10 mg), d?chlorob?s(t?phenylphosphine)pallad?um (II) (36 mg) and triethylamine (3 5 ml_) were heated in a Reacti-vial at 7O0C overnight. The reaction was cooled to room temperature, partitioned between saturated sodium bicarbonate solution and DCM, separated using a hydrophobic frit and the organics were evaporated in vacuo The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 0- 100% EtOAc in cyclohexane to give the title compound. MS calcd for (C31H34N2O6 + H)+- 531 MS found (electrospray)- (M+H)+ = 531 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pyridine; cyclohexane; ethyl acetate; | 2.0 g (10.24 mmol) of 1,1-dimethylethyl (S)-2-ethynyl-1-pyrrolidinecarboxylate and 2.26 g (10.24 mmol) of <strong>[40263-57-8]2-iodopyridin-3-ol</strong> are dissolved in 50 ml of pyridine, under an argon atmosphere, in a 100 ml three-necked round-bottomed flask. 0.88 g (6.15 mmol) of copper(I) oxide is added and the mixture is heated at reflux for 24 h. The solution is filtered through paper and the solvent is evaporated under reduced pressure. The residue is purified by chromatography on silica gel, elution being carried out with a 60/40 and then 50/50 mixture of cyclohexane and ethyl acetate. 2.43 g of product are thus obtained in the form of a thick oil. [α]D20 =-102.6 (c=1, CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In thiophene; acetone; | (c) 3-Hydroxy-2-iodo-1-(4-dodecylbenzyl)pyridinium bromide A mixture of <strong>[40263-57-8]3-hydroxy-2-iodopyridine</strong> (22.1 g, 0.1M) and 4-dodecylbenzyl bromide (37.2 g, 0.101M) was stirred in sulpholane (100 ml) at 90 C. for 8 hours. Acetone was added and the precipitated product filtered and washed with acetone to yield a white solid (45 g). The product was recrystallized from a mixture of methanol and water, collected and dried at 60 C. (35 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; caesium carbonate; In N-methyl-acetamide; | A. 152.6 g of potassium carbonate and 15.3 g of cesium carbonate are added to a solution of 122 g of <strong>[40263-57-8]3-hydroxy-2-iodopyridine</strong> and 65.7 ml of benzyl bromide in 1.5 l of dimethylformamide, and the suspension is stirred under argon atmosphere for 20 hours at room temperature. The reaction mixture is filtered, the filter residue is washed with dichloromethane, the filtrate is concentrated by evaporation, and the residue is chromatographed on silica gel with hexane/10-20% ethyl acetate. 146.3 g of 3-benzyloxy-2-iodopyridine is obtained as oil. IR(CHCl3): 2980, 1552, 1438, 1402, 1371, 1067, 1002, 908 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 90℃; for 4h;Product distribution / selectivity; | To 4-bromophenylactetylene (4.3 g) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (5.25 g), bis(triphenylphosphine)palladium dichloride (1.5 g), copper (I) iodide (0.58 g) and triethylamine (100 ml_). The reaction was stirred at 9O0C1 under nitrogen, for 4 h. The reaction was cooled, diluted with EtOAc (400 ml.) and washed twice with saturated ammonium chloride solution, brine and then concentrated. The crude product was dissolved in DCM, filtered and purified by ISCO companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane (30-100%) to give the title compound. MS calcd for (C13H8BrNO + H)+: 274/276 MS found (electrospray): (M+H)+ = 274/276 | |
A suspension of bis(triphenylphosphine)palladium dichloride (92 mg) and copper (I) iodide (430 mg) in DMF (7.5 ml.) was treated with triethylamine (4.6 mL) and heated to 7O0C. 4- Bromophenylacetylene (3.98 g) and <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (6.12 g) were dissolved in DMF (13 mL) and added dropwise to the mixture over 80 min. The mixture was heated at 7O0C for 19 h and cooled to 370C. Water (45 mL) was added over 10 min and the resulting suspension was filtered, washing with 1 :1 DMF:water (2 x 60 mL) and then water (40 mL). The wet solid was suspended in 3:1 toluene: MeOH (70 mL), heated to reflux for ~ 30 mins and cooled. Charcoal (1.13 g) was added and the mixture was refluxed for 1 h. The mixture was cooled, filtered through silica (11.3 g) and washed with 3:1 toluene:MeOH (2 x 20 mL). The filtrate was concentrated to 80% of its volume and iso-propanol (60 mL) was added. The mixture was further concentrated to 80% of its volume, and the suspension was then allowed to cool to ambient temperature overnight. The mixture was cooled further to 50C, filtered and washed with cold iso-propanol (2 x 9 mL). The solid was dried in vacuo to give the title compound.1H NMR (d6-DMSO):. δ 8.51 (1 H, bd), 8.05 (1 H, d), 7.93 (2H, d), 7.8-7.7 (3H, m), 7.35 (1 H, dd). | ||
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 90℃; for 4h; | To 4-bromophenylactetylene (4.3 g) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (5.25 g), bis(triphenylphosphine)palladium dichloride (1.5 g), copper (I) iodide (0.58 g) and triethylamine (100 ml_). The reaction was stirred at 9O0C, under nitrogen, for 4 h. The reaction was cooled, diluted with EtOAc (400 ml.) and washed twice with saturated ammonium chloride solution, brine and then concentrated. The crude product was dissolved in DCM, filtered and purified by ISCO companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane (30-100%) to give the title compound. MS calcd for (C13H8BrNO + H)+: 274/276 MS found (electrospray): (M+H)+ = 274/276 |
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 50℃; for 3h; | Intermediate 39 2-(4-Bromophenyl)furo[3,2-b]pyridineTo 4-bromophenylactetylene (1.65 g) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (2.02 g), bis(triphenylphosphine)palladium dichloride (575 mg), copper (I) iodide (225 mg) and triethylamine (35 ml_). The reaction was stirred at 5O0C, under nitrogen, for 3 h. The reaction was cooled, diluted with DCM (250 ml_) and washed with saturated ammonium chloride solution, brine and then concentrated. The crude product was purified by ISCO companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane to give the title compound.MS calcd for (C13H8BrNO + H)+: 274/276MS found (electrospray): (M+H)+ = 274/276 | |
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 50℃; for 3h; | Intermediate 4 2-(4-Bromophenyl)furo[3,2-]pyridineTo 4-bromophenylactetylene (1.65 g) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (2.02 g), bis(triphenylphosphine)palladium dichloride (575 mg), copper (I) iodide (225 mg) and triethylamine (35 mL). The reaction was stirred at 5O0C, under nitrogen, for 3 h. The reaction was cooled, diluted with DCM (250 mL) and washed with saturated ammonium chloride solution, brine and then concentrated. The crude product was purified by ISCOCompanion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane to give the title compound.MS calcd for (C13H8BrNO + H)+: 274/276 MS found (electrospray): (M+H)+ = 274/276 | |
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; at 90℃; for 4h;Neat (no solvent); | Intermediate 3 2-(4-Bromophenyl)furo[3,2-b]pyridineT )> <( ))- BrTo 4-bromophenylactetylene (4.3 g) was added <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (5.25 g), bis(triphenylphosphine)palladium dichloride (1.5 g), copper (I) iodide (0.58 g) and triethylamine (100 mL). The reaction was stirred at 9O0C, under nitrogen, for 4 h. The reaction was cooled, diluted with EtOAc (400 mL) and washed twice with saturated ammonium chloride solution, brine and then concentrated. The crude product was dissolved in DCM, filtered and purified by ISCO Companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane (30-100%) to give the title compound. MS calcd for (Ci3H8BrNO + H)+: 274/276 MS found (electrospray): (M+H)+ = 274/276 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 70℃; for 3h; | Intermediate 47Ethyl 1 -(4-furo[3,2-]pyridin-2-ylphenyl)-3-[[(fraϖs-4-methylcyclohexyl)carbonyl](1 - methylethyl)amino]-1H-pyrazole-4-carboxylateA solution of Intermediate 46 (3.49 g) in triethylamine (25 mL) was divided into 5 equal portions and each portion placed in a Reactivial and each treated with 3-hydroxy-2-iodo- pyridine (0.18 g), copper (I) iodide (0.016 g) and dichlorobis(triphenylphosphine)palladium (0.058 g). The Reactivials were stirred and heated at 7O0C for 3 h, then allowed to cool and the contents of each one combined, diluted with DCM and washed with saturated ammonium chloride solution, brine, dried (Na2SO4) and evaporated to give a foam. The foam was purified by chromatography on silica gel using a cyclohexane /ethyl acetate gradient to give the title compound. MS calcd for (C30H34N4O4+ H)+ : 515 MS found (electrospray): (M+H)+ = 515 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;copper(I) iodide; In N,N-dimethyl-formamide; | EXAMPLE 35a 2-(diethoxymethyl)furo[3,2-b]pyridine 2-Iodo-3-pyridinol (24 mmol), triethylamine (1.0 eq), 3,3-diethoxy-1-propyne (1.0 eq), bis(triphenylphosphine)palladium (II) chloride (0.02 eq), and copper(I) iodide (0.04 eq) were combined in DMF (14 mL) and allowed to stir for 17 hours. The mixture was diluted with ethyl acetate (100 mL) and filtered through a Celite pad. The filtrate was washed with saturated sodium bicarbonate (2*50 mls), dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ1.28 (t, J=7.1 Hz, 6H), 3.70 (q, J=7.1 Hz, 4H), 5.68 (s, 1H), 7.05 (s, 1H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 8.57 (br, 1H). MS (DCI/NH3) m/z 222 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 70℃; | Intermediate 150 (250 mg), 2-iodo-3-pyridinol (125 mg), copper (I) iodide (10.7 mg) and dichlorobis(triphenylphosphine)palladium (II) (39 mg) were dissolved in triethylamine (3.5 ml_) and were heated in a Reacti-vial at 7O0C overnight. The reaction was partitioned between saturated sodium bicarbonate solution and DCM. The organics were dried using a hydrophobic frit and were evaporated in vacuo. The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 5-100% EtOAc in cyclohexane to give the title compound. MS calcd for (C29H32N2O4S2 + H)+: 537 MS found (electrospray): (M+H)+ = 537 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; | Example 7; 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine; 13 To a solution containing <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> 12 (1.85 g, 8.37 mmol), 2-(3-thienyl)ethanol (1.20 mL, 10.9 mmol), and triphenylphosphine (2.85 g, 10.9 mmol) in tetrahydrofuran (46.2 mL, 5.70 mmol) was added diisopropyl azodicarboxylate (2.14 mL, 10.9 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and purified by flash chromatography EtOAc/Hex (0-100%) eluted at 30% to give 13 (yield 90%). MS: (ESI+) 332.2 |
90% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 18h; | Step 1: 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine To a solution containing <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (1.85 g, 8.37 mmol), 2-(3-thienyl)ethanol (1.20 mL, 10.9 mmol), and triphenylphosphine (2.85 g, 10.9 mmol) in tetrahydrofuran (46.2 mL, 5.70 mmol) was added diisopropyl azodicarboxylate (2.14 mL, 10.9 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and purified by flash chromatography EtOAc/Hex (0-100%) eluted at 30% to give 2-Iodo-3-(2-thiophen-3-yl-ethoxy)-pyridine (yield 90%). MS: (ESI+) 332.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene (prepared as described in PCT Int. Appl. WO2006064189, 0.292 g, 1.10 mmol), <strong>[40263-57-8]2-iodo-3-hydroxypyridine</strong> (Aldrich, 0.177 g, 0.801 mmol), and tetrakis (triphenylphosphino)palladium(0) (Aldrich, 0.048 g, 0.042 mmol) were dissolved in 1,4-dioxane (9 mL), treated with 2M aqueous Na2CO3 (2.0 mL, 4.0 mmol), bubbled with argon for a few minutes, and heated to 100 C. under reflux condenser for 24 h. After cooling to ambient temperature, the reaction was diluted with water (30 mL), extracted thrice with dichloromethane, aqueous layer acidified to ca. pH 7, extracted twice more with dichloromethane, and the combined organic layers washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give an orange oil. This was purified by thin layer chromatography on silica gel (EtOAc) to give the title compound as a yellow solid.1H NMR (400 MHz, CHLOROFORM-d) δ 8.16 (dd, J=4.5, 1.3 Hz, 1H), 7.22 (dd, J=8.1, 1.3 Hz, 0H), 7.07 (dd, J=8.2, 4.7 Hz, 1H), 5.95-6.09 (m, 2H), 4.03 (s, 4H), 2.73 (dddd, J=6.4, 4.4, 2.2, 2.0 Hz, 2H), 2.49 (d, J=2.8 Hz, 2H), 1.96 (t, J=6.6 Hz, 2H). ESI-MS (m/z): Calcd. For C13H15NO3: 233. found: 234 (M+H). | ||
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 24h;Inert atmosphere; | Example 1 : N-( l-(4-( 3-hvdroxypyridin-2-yl)cvclohexyl)azetidin-3-yl)-2-( ( 6- ftrifluoromethyl) uinazolin-4-yl)amino)acetamideStep A: 2-(l,4-Dioxa-spiro[4.5]dec-7-en-8-yl)-pyridin-3-ol; 8-(4,4,5,5-Tetramethyl-[l,3,2]dioxaborolan-2-yl)-l,4-dioxa-spiro[4.5]dec-7-ene(prepared as described in PCT Int. Appl. WO2006064189, 0.292 g, 1.10 mmol), 2-iodo-3- hydroxypyridine (Aldrich, 0.177 g, 0.801 mmol), and tetrakis (triphenylphosphino)palladium(O) (Aldrich, 0.048 g, 0.042 mmol) were dissolved in 1,4-dioxane (9 mL), treated with 2M aqueous Na2C03 (2.0 mL, 4.0 mmol), bubbled with argon for a few minutes, and heated to 100 C under reflux condenser for 24 h. After cooling to ambient temperature, the reaction was diluted with water (30 mL), extracted thrice with dichloromethane, aqueous layer acidified to ca. pH 7, extracted twice more with dichloromethane, and the combined organic layers washed with brine, dried over Na2S04, filtered, and concentrated in vacuo to give an orange oil. This was purified by thin layer chromatography on silica gel (EtOAc) to give the title compound as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.16 (dd, J=4.5, 1.3 Hz, 1 H), 7.22 (dd, J=8.1, 1.3 Hz, 0 H), 7.07 (dd, J=8.2, 4.7 Hz, 1 H), 5.95 - 6.09 (m, 2 H), 4.03 (s, 4 H), 2.73 (dddd, J=6.4, 4.4, 2.2, 2.0 Hz, 2 H), 2.49 (d, J=2.8 Hz, 2 H), 1.96 (t, J=6.6 Hz, 2 H). ESI-MS (m/z): Calcd. For Ci3Hi5N03: 233; found: 234 (M+H). |
A191659 [59288-40-3]
Ethyl 5-hydroxy-6-iodonicotinate
Similarity: 0.68
A191659 [59288-40-3]
Ethyl 5-hydroxy-6-iodonicotinate
Similarity: 0.68