Structure of 2-(2-Chloroethoxy)acetic acid
CAS No.: 14869-41-1
*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. : | 14869-41-1 |
Formula : | C4H7ClO3 |
M.W : | 138.55 |
SMILES Code : | O=C(O)COCCCl |
MDL No. : | MFCD17014832 |
InChI Key : | MHXJETVNZPUVEN-UHFFFAOYSA-N |
Pubchem ID : | 10920584 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 28.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.6 |
Solubility | 34.9 mg/ml ; 0.252 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.8 |
Solubility | 22.1 mg/ml ; 0.159 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.8 |
Solubility | 22.2 mg/ml ; 0.16 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 |
-6.96 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 |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
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) |
2.22 |
* 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 thionyl chloride;N,N-dimethyl-formamide; at 60℃; for 1 - 16h;Product distribution / selectivity; | 1.39 g (10.0 mmol) 2-<strong>[14869-41-1](2-chloro-ethoxy)-acetic acid</strong> are heated to 60° C. for 1 h with 1 drop of DMF in 8.0 ml of thionyl chloride and then evaporated down completely i. vac. The residue is added in 5 ml THF to a mixture of 1.18 g (10.0 mmol) 4-amino-benzonitrile and 4.5 ml (32.5 mmol) TEA in 20 ml THF at 0° C. and rinsed with 5 ml THF. Then the mixture is stirred for 16 h at ambient temperature. After evaporation i. vac. the residue is combined with ethyl acetate, washed with 2N hydrochloric acid and sat. sodium hydrogen carbonate solution and dried on sodium sulphate. After evaporation i. vac. the residue is purified by chromatography on silica gel (eluant gradient: petroleum ether/ethyl acetate=6:1-->3:1). Yield: 1.82 g (76percent) Rf value: 0.43 (silica gel, petroleum ether/ethyl acetate 1:1) C11H11ClN2O2 (238.67) Mass spectrum: (M-H)-=237/239 (chlorine isotopes); (c) 2-<strong>[14869-41-1](2-chloro-ethoxy)-acetic acid</strong>-chloride13.86 g (100 mmol) 2-<strong>[14869-41-1](2-chloro-ethoxy)-acetic acid</strong> are combined with 15 ml (207 mmol) thionyl chloride at ambient temperature and 3 drops of DMF are added. The mixture is stirred for 16 h at 60° C. Then it is evaporated down i. vac., the residue is distilled i. vac. and the overflow is collected at 75-78° C.Yield: 12.90 g (82percent)C4H6Cl2O2 (157.00)Mass spectrum: (M+H)+=157/159/161 (chlorine isotopes) |
With thionyl chloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2.5h; | 2-Chlorethoxyacetic acid (1.11 g, 8 mmol) is dissolved in dichloromethane (22 mL), and thereto are added thionyl chloride (1.17 mL, 16 mmol) and dimethylformamide (30 muL, 0.4 mmol) successively at room temperature. After stirring at room temperature for 2.5 hours, the mixture is concentrated, and the residue is dissolved in dichloromethane (22 mL). To the mixture are added methyl 4-aminobenzoate (661 mg, 4 mmol) and pyridine (674 muL, 8 mmol) under ice-cooling, followed by stirring overnight. The reaction solution is washed with dilute hydrochloric acid, dried, and concentrated. The residue is subjected to silica gel column chromatography to give ethyl 4-(2-chloroethoxyacetylamino)benzoate (540 mg, 23.6percent). | |
With oxalyl dichloride; at 20℃; for 8h; | Step 2: 2-(2-Chloroethoxy)acetyl Chloride (c-3); oCl ^" ^ ClTo the acid, oxalyl chloride (50 mL), was added. The reaction was stirred at room temperature for 8 h. The solids were filtered and washed with DCM. The volatiles were removed and to give the product (560 mg), as a light yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-c/), delta ppm 3.67 (t, J=5.5 Hz, 2 H), 3.88 (t, J=5.7 Hz, 2 H), 4.52 (s, 2 H). |
With thionyl chloride; at 60℃; for 1h; | 2-(2-Chloroethoxy)acetyl chloride combined with thionyl chloride (9.51 ml, 130 mmol) and heated at 60 °C for lh. Thionyl chloride was removed in vacuum and resulting liquid was used without purification. | |
With oxalyl dichloride; In dichloromethane; at 20℃; for 4h; | 2-(2-Chloroethoxy)acetic acid (1.0 g, 7.2 mmol) was dissolved in dichloromethane (10.0 mL)Then oxalyl chloride (1.2 mL, 14 mmol) was added and stirred at room temperature for 4 hours.Evaporate the solvent under reduced pressure.The crude product was used directly in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | 150 ml dichloromethane, 60 ml tap water, 30.0 ml 2-(2-chloroethoxy)ethanol (XI), 28.52g sodium hydrogencarbonate, and Q.22g TEMPO catalyst are measured to a sulfonating flask equipped with condenser, thermometer, dropping funnel. Then at roo temperature 240.0 ml solution of 55.62g calcium-hypochlorite in tap water is added from the dropping funnel. The mixture is stirred for a further half an hour, then 1.34g sodium metabisulfite is added to the reaction mixture, the two phases are separated in a separation funnel, then the aqueous phase is washed with 2x10 ml dichloromethane. Then the aqueous phase is acidified to pH=T-2 with 34% hydrochloric acid solution. The obtained aqueous solution is extracted with 5x50 ml methyl isobutyl ketone. The combined organic extract is washed with 1x20 ml saturated salt solution, then at a reduced pressure evaporated to constant mass. (0073) The mass of the obtained pale yellow oil : 28.4g, yield 72%. | |
19.3% | Ethyleneglycol mono 2-chloroethyl ether (10 g, 0.08 mol) is added to an aqueous 30% hydrogen peroxide solution (22.8 g, 0.2 mol) and thereto are added sodium tungustate dihydrate (0.53 g, 1.6 mmol) and trioctylmethylammonium sulfate (0.75 g, 1.6 mmol). The mixture is stirred at 90C for 4 hours. After adding aqueous sodium thiosulfate solution, the mixture is extracted with ethyl acetate (50 mL). The organic layers are combined, washed, dried and concentrated to give oily residue (9 g). The residue is diluted with diethyl ether, and the insoluble materials are removed by filtration. The filtrate is partitioned by adding aqueous sodium bicarbonate. The aqueous layer is washed with diethyl ether and acidified with dilute hydrochloric acid, followed by extraction with ethyl acetate. The organic layers are combined, dried, and concentrated to give 2-chloroethoxyacetic acid (2.14 g, crude, 19.3%) as oily residue. IR: nu = 3410, 1727, 1123, 1044 cm-1 | |
With chromium(VI) oxide; sulfuric acid; In dichloromethane; water; at 0℃; for 0.5h; | Scheme C; <n="42"/>Step 1 : 2-(2-Chloroethoxy)acetic Acid (c-2); oHO ^^ ^^ ClTo concentrated H2SO4 (6 ml_) was added CrO3 ( 4 g, 40.1 mmol). To this mixture ice water (15 mL), was added dropwise. Once all the material was dissolved, the solution was added dropwise to 5 g of silica gel while stirring. To the adsorbed Jones's reagent, 50 mL of DCM were added and the mixture was cooled to 0 0C. A solution of the alcohol (1.00 g, 8.03 mmol), was added dropwise and stirred for 30 min. The reaction was filtered and the silica cake was washed with DCM (100 mL). The solvent was removed and the residue was fractioned between ether (3 x 20 mL), and 10 % aqueous K2CO3 (3 x 50 mL). The organic layer was discarded and the aqueous layer was taken to pH=1 with aqueous 3 N HCI. The aqueous layer was saturated with Na2SO4 and extracted with MeCN. The organic layer was concentrated and the residue dissolved in 50 mL of DCM. The solution was dried over Na2SO4 and concentrated to give 0.8 g of a colorless oil, which was used without further purification. 1H NMR (400 MHz, DMSO-c/6): delta 3.73 (s, 4 H), 4.07 (s, 2 H), 12.72 (br s., 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
C. Preparation of 2-chloroethoxy acetic acid This compound was prepared by treating 120 g. of the product obtained in Example 573 with 250 ml. of concentrated HCl. Reaction sets in after a short time, and it is necessary to cool the flask to control the reaction, which is finally completed by heating on a steam bath for two hours. The mixture is diluted with an equal volume of water, and extracted four times with 50 cc portions of ether. The ether is evaporated and the product is distilled in vacuum, b3-5 130°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With ammonium acetate; hydrogenchloride; In ethanol; water; isopropyl alcohol; | I.1.4. 2-(1-Piperazinyl)ethoxyacetic Acid 8.6 g (0.1 mol) of piperazine, 17.7 g (0.1 mol) of piperazine dihydrochloride and 50 ml of water are introduced into a 100 ml three-necked round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is brought to a temperature of 70° C. 15.2 g of (2-chloroethoxy) acetic acid are then added dropwise over 15 minutes. The mixture is brought to a temperature of 80° C. with stirring and is maintained at this temperature for 27 hours. The mixture is allowed to cool to room temperature and the water is evaporated off under reduced pressure on a rotary evaporator. The evaporation residue is taken up in 50 ml of ethanol and maintained at 50° C. with stirring for 45 minutes. It is then placed in an ice bath and is stirred for 1 hour. The precipitate (piperazine dihydrochloride) formed is then filtered off and the solvents are evaporated off under reduced pressure on a rotary evaporator at 50° C. 22.4 g of a yellow oil are obtained. 10 g of this mixture are purified on 130 g of Amberlyte IRA-400 resin. Elution is carried out first with 600 ml of water and then with aqueous 0.5 M ammonium acetate solution. The fractions containing the 2-(1-piperazinyl)ethoxyacetic acid or its salt are combined and the water is removed therefrom under reduced pressure at 60° C. on a rotary evaporator. 18.2 g of a mixture containing white crystals and an oil are recovered. This mixture is taken up in 75 ml of isopropanol and the insoluble crystals are filtered off. The filtrate is acidified with 20 ml of a 9N solution of hydrochloric acid in ethanol. The precipitate formed is filtered off quickly, washed with isopropanol and dried on a rotary evaporator under reduced pressure at 50° C. 7.1 g of a white solid are obtained, which solid is purified by subliming the ammonium chloride salts (4 hours at 135° C. under 0.1 mbar and then 8 hours at 150° C. under 0.1 mbar). 1.4 g of 2-(1-piperazinyl)ethoxyacetic acid dihydrochloride are thus obtained. Yield: 12percent NMR: delta: 2.36 (2H, t, 4.8 Hz); 3.45 (4H, m); 3.53 (4H, m); 3.88 (2H, t, 4.8 Hz); 4.09 (2H, s); 10 (1H, bs). Mass spectrum: 189 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; water; for 2h; | Example 10; ri-R.2lSf)-2-r{r(3i?,3^6ai?Vhexahvdrofuror2,3-lfuran-3-yloxylcarbonvnaminoVl- { [Cl ,3-benzodioxol-5-ylsulfonylVisobutyl)amino]methyl) -3- {4-r(2-methyl- 1 ,3-thiazol- EPO <DP n="44"/>4- yP)methoxy]phenyl } propyl \\2-( lH-imidazol- 1 - ypethoxy] acetate bis-trifluoroacetic acid salt; Example 10, step 1; (2-chloroethoxy)acetic acid; A solution of tert-butyl 2-(2-chloroethoxy)acetate (Hernandaz, Pedro E.; Fairfax, David E.; Michalson, Erik T. Process for preparing piperazine-substituted aliphatic carboxylates. PCT Int Appl. (200I)5 WO 0129016 Al 20010426 CAN 134:311229 AN 2001:300697) (1.00 g, 5.14 mmol) and concentrated hydrochloric acid (10 mL) was stirred for 2 hours. The reaction solution was diluted with water (20 mL) and extracted with ethyl ether (3x350 mL). The etheral layers were combined, washed with water (2 x 20 mL) and concentrated in a vacuum. The residue was dissolved in dichloromethane (60 mL) and concentrated in a vacuum (3x) to afford 2-(2-chloroethoxy)acetic acid as a clear oil (680 mg, 95 percent). 1H NMR (400 MHz, DMSO-d6) delta 8.4 (br s, IH), 4.22 (s, 2H), 3.85 (t, 2H, J = 5.9 Hz), 3.67 (t, 2H, J = 5.9). ES-LCMS m/z 139 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 24h; | Example 10, step 2; (li-,26)-2-([(3i?,3a5',6ai?)-hexahydrofuro[2,3-]furan-3-yloxy]carbonyl}amino)-l- { [( 1 ,3 -benzodioxol-5-ylsulfonyl)(isobutyl)amino]methyl} -3- {4-[(2-methyl- 1 ,3 -thiazol- 4-yl)methoxy]phenyl}propyl (2-chloroethoxy)acetate; EPO <DP n="45"/>To solution of (3izeta3a.pound.,6ai?)-hexahydrofuro[2,3-b]furan-3-yl (lS,2R)-3-[(l,3- benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-l-{4-[(2-methyl-l,3-thiazol-4- yl)methoxy]benzyl}propylcarbamate ( 2.13 mmol, 1.50 g), <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (4.93 mmol, 0.680 g), and 4-(dimethylamino)pyridine (200 mg) in anhydrous N,N- dimethylformamide (15 mL) while stirring under a nitrogen atmosphere, was added N- [3-(dimethylamino)propyl]-N-emylcarbodiimide hydrochloride (7.83 mmol, 1.50 g,) and stirring was continued for 24 hours. Chromatographic purification (silica gel, isopropanol/dichloromethane gradient, 0 to 15percent) afforded (lR,2S)-2-([(3R,3aS,6aR)- hexahydrofuro[2,3-delta]furan-3-yloxy]carbonyl}amino)-l-[(l,3-benzodioxol-5- ylsulfonyl)(isobutyl)amino]methyl}-3-{4-[(2-methyl-l,3-thiazol-4- yl)methoxy]phenyl}propyl (2-chloroethoxy)acetate as a white foam (1.62 g, 92 percent). 1H NuMR (400 MHz, DMSO-d6) delta 8.52-8.55 (m, IH), 7.55-7.58 (m, IH), 7.47-7.50 (m, IH), 7.33-7.38 (m, 2H), 7.20-7.25 (m, IH), 7.10-7.13 (m, 2H), 6.85-6.93 (m, 2H), 6.55- 6.60 (m, 2H), 5.96 (s, 2H), 5.46-5.51 (m, IH), 5.11 (s, 2H), 4.91-4.98 (m, IH), 4.78-4.85 (m, IH), 3.70-3.79 (m, IH), 3.62-3.69 (m, IH), 3.55-3.61 (m, 3H), 3.42-3.51 (m, IH), 3.21-3.30 (m, 2H), 2.86-2.98 (m, 2H), 2.70-2.78 (m, IH), 2.56-2.66 (m, 2H), 2.32-2.40 (m, IH), 1.86-1.95 (m, IH), 1.25-1.40 (m, IH), 1.15-1.24 (m, IH), 0.98-1.03 (m, 4H), 0.75-0.85 (m, 6H). ES-LCMS m/z 824 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In N,N-dimethyl-formamide; at 20℃; | To a suspension of compound 26-5 (0 1 g) and 2-chloroethoxy acetic acid (45 4 mg) m DMF (2 mL), was added4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholmium chloride (DMT-MM, 87 7 mg) The reaction mixture was stirred at room temperature overnight Then, according to the Step 29-1 in synthetic method for EXAMPLE 29, cychzation reaction was pursued to obtain compound 30-1 (90 mg) as a colorless amorphous solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphorus(III) oxide; methanesulfonic acid; at 20 - 30℃; for 2h; | Example 64In a three-necked round-bottom flask equipped with a mechanical stirrer, a thermometer, a condenser and a dropping funnel 2.77 g (20 mmol) 5-chloro-3- oxapentanoic acid was mixed with 15 ml methanesulfonic acid. 1.10 g (5 mmol) P406 was added drop-wise at 30 °C. After completed addition the reaction mixture was stirred for 2 h at 20 °C. During the reaction time the evolution of CO was observed. Then 3 ml H20 was added and the obtained liquid analysed by 1 H- and 31 P-NMR spectroscopy. 4-Chloro-2-oxabutanyl-1-phosphonic acid was detected at 78.1 percentw/w | |
In a three-necked round-bottom flask under nitrogen atmosphere equipped with a mechanical stirrer, a thermometer, a condenser and a dropping funnel 6.87 g (0.05 mol) phosphorus trichloride and 10.75 g (0.05 mol) Amberlyst-15 (hydrogen form, dry) were mixed with 50 ml chlorobenzene . Slowly 6.90 g of (0.05 mol) 5-chloro-3- oxapentanoic acid was added drop-wise. After completed addition the reaction mixture was heated to 50 °C for 4 h. During the addition and reaction time the evolution of CO was observed. Then 10 ml water was added and the Amberlyst- 15 was filtered off. The solution was analyzed by ChiEta- and 31P-NMR spectroscopy and 4-Chloro-2-oxabutanyl-l-phosphonic acid observed at 58.9 percentw/w. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
484 mg | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; acetonitrile; at 0 - 25℃; for 18h; | Compounds 4530a (490 mg, 1.03 mmol) and 4530b (0.15 mE, 1.24 mmol) were dissolved in CH2C12 (10 mE)?CH3CN (5 mE) at 0° C. EDC1 (238 mg, 1.24 mmol) and DMAP (13.5 mg, 0.11 mmol) were added to the solution and the mixture was stirred at 00 C. to 25° C. for 18 h. Themixture was added to aqueous NaHCO3 solution and the organic layers were extracted by CH2C12 and the combined organic solution was washed with brine, dried (Na2504), and concentrated in vacuo. The residue was purified by silica gel colunm chromatography (CH2C12 to 8percent MeOR inCH2C12, gradient) to afford a pure compound 4530c (484 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Step A: To DCM (2.0 mL) was added HATU (125 mg, 0.33 mmol) and <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (46 mg, 0.33 mmol) in DCM (0.5 mL), followed by added DIPEA (76 mg 0.60 mmol) at 25 °C and stirred at 25 °C for 0.5 hour. Then 6-(3-amino-3-azabicyclo[3.1.0]hexan-6-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro -1H-pyrazolo[3,4-c]pyridine-3-carboxylate ethyl (123 mg, 0.30 mmol) in DCM (0.5 mL) was added to the reaction mixture at 25 °C and stirred at 25 °C for 16 hours. The mixture was poured into saturated NaHCO3 solution (10 mL), extracted with DCM (10 mL x 2). The combined organic layers were dried, filtered, concentrated. The crude residue was purified by salica gel column chromatography (DCM : EA = 1:1 to 0:1) to give ethyl 6-(3-(2-(2-chloroethoxy)acetamido)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (80 mg, 50percent) as a yellow oil. LCMS (ESI) m/z: 532(M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 25℃; for 16.5h; | Step F: To a solution of <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (181 mg, 1.31 mmol) in DCM (5 mL) was added HATU (399 mg, 1.05 mmol) and DIEA (225 mg, 1.75 mmol). The mixture was stirred for 30 min before ethyl methyl 5-(((allyloxy) carbonyl)(1-aminopiperidin-4-yl)carbamoyl)-1-(4-methoxyphenyl)-1H-pyrazole-3-carboxy late (400 mg, 0.875 mmol) was added. The reaction mixture was stirred at 25 °C for 16 hours. The mixture was poured into water (20 mL), extracted with DCM (30 mL x 2), dried over anhydrous Na2SO4, and concentrated. The crude residue was purified by silical gel chromatography (PE : EA = 5:1 to 1:1) to give ethyl methyl 5-(((allyloxy)carbonyl)(1-(2-(2-chloroethoxy)acetamido)piperidin-4-yl)carbamoyl)-1-(4-m ethoxyphenyl)-1H-pyrazole-3-carboxylate (400 mg, 79percent) as a yellow solid. LCMS (ESI) m/z: 578 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.8 g | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 12℃; for 16h; | Step F: To DMF (30 mL) was added <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (0.93 g, 6.7 mmol), HATU (2.6 g, 6.7 mmol) and DIPEA (2.6 mL), followed by added a solution of 6-(1-aminopiperidin-4-yl)-3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-5,6-dih ydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one (2.4 g, 5.6 mmol) in DMF (10 mL) at 12 °C. The mixture was stirred at 12 °C for 16 hours. After water was added, the mixture was extracted with EtOAc (100 mL x 2). The combined organic layers were washed with aqueous sodium hydrogen carboante solution, dried over anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography (PE : EA = 1:1 to 0:1) to give 2-(2-chloroethoxy)-N-(4-(7-oxo-3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-4 ,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)piperidin-1-yl)acetamide (2.8 g, 92percent) as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
900 mg | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 25℃; for 16h; | Step H: To a solution of <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (342 mg 2.47 mmol) in DMF (10 mL) was added HATU (939 mg, 2.47 mmol), DIEA (532 mg, 4.12 mmol), and then 6-(1-aminopiperidin-4-yl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyraz olo[3,4-c]pyridin-7(4H)-one (900 mg crude, 2.06 mmol). The mixture was stirred at 25 °C for 16 hours. The mixture was poured into water (80 mL), extracted with EA (60 mL x 2). The combined organics were dried over anhydrous Na2SO4, concentrated. The crude residue was purified by silical gel chormatography (PE : EA = 1:1 to EA) to give 2-(2-chloroethoxy)-N-(4-(1-(4-methoxyphenyl)-7-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)piperidin-1-yl)acetamide (900 mg, 82percent) as a yellow solid. LCMS (ESI) m/z: 530.2 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | Step F: To DMF (150 ml) was added 2-(2-chloroethoxy) acetic acid (6.2 g, 0.0449 mol), HATU (18.6 g, 0.049 mol), DIEA (6.8 g, 0.049 mol). The mixture was stirred at 30 °C for 20 minutes, then 2-(1-aminopiperidin-4-yl)isoindoline-1,3-dione (10.0 g, 0.0408 mol) was added. The mixture was stirred at 30°C for 16 hours. After the reaction completed, the mixture was poured into water (200 ml), white solid was separated out, filtrated. The solid was dissolved in DCM (300 ml), dried over anhydrous Na2SO4, filtered. The filtrate was concentrated to get the desired product (12.5 g, 83.9percent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃; for 12h; | Step A: To DCM(20 mL) was added ethyl 6-(1-aminopiperidin-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3, 4-c]pyridine-3-carboxylate (1.00 g, 2.42 mmol) and 2-(2-chloroethoxy) acetic acid (0.40 g, 2.91 mmol). DIPEA (1.2 mL, 7.2 mmol) and HATU (0.95 g,2.5 mmol) was added into the solution. The mixture was stirred at room temperature for 12 hours. The mixture was poured into water (40 mL) and extracted with DCM (20 mL x 3). The combined organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to give ethyl 6-(1-(2-(chloromethoxy)acetamido)piperidin-4-yl)-1-(4-methoxyphenyl)-oxo-4,5,6,7-tetra hydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (1.00 g, crude) as a yellow solid. LCMS (ESI) m/z: 534(M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | In a glass RBF equipped with a Teflon-coated magnetic stirrer was dissolved (2-chloro-ethoxy)- acetic acid (1 eq.) in dichlormethane (0.67 M). To this was then added sequentially pyridine (2.5 eq.) and thionyl chloride (1.5 eq.), the latter of which was added drop-wise over 10 mm. The resulting orange solution was stirred at RT under nitrogen for 30 mm before 2-bromo-4-fluoro-5- nitro-phenylamine (1 eq.) was added drop-wise as a solution in dichloromethane (0.67 M). Finally, triethylamine (3.5 eq.) and DMAP (0.1 eq.) were added and the resulting mixture was allowed to stir at RT for 18 h. The reaction was quenched with the addition of water and extracted with EtOAc. The combined organic extracts were then washed further with water and brine, dried over MgS 04, filtered and the filtrate concentrated in vacuo. Further purification by way of column chromatography (Si02, gradient elution, 9:1 (v/v) Hex: EtOAc - EtOAc) furnish the desired product as an orange oil that solidified upon standing (51percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; | In a glass RBF equipped with a Teflon-coated magnetic stirrer was dissolved 4-fluoro-2-methoxy-5- nitro-phenylamine (1 eq.) in DMF (0.32 M). To this was then added sequentially HATU (1.2 eq.), DMAP (0.1 eq.), <strong>[14869-41-1](2-chloro-ethoxy)-acetic acid</strong> (1.1 eq.) and finally ethyl-diisopropylamine (3 eq.). When the reaction was deemed to be complete by LCMS (14 h), the reaction mixture was diluted with EtOAc and washed sequentially with 10percent aq. HC1, sat. aq. NaHCO3, water and brine. The organic extract was then dried over MgSO4 and filtered. Concentration of the filtrate thus obtained in vacuo furnished the desired product as a tan solid (99percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; In tetrahydrofuran; at 60℃; for 4h; | A mixture of <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (48 mg,0.34 mmol), compound 23 (200 mg, 0.34 mmol) and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline(100 mg, 0.41 mmol) in THF (4 mL) was stirred at 60 C for 4 h when TLC analysis indicated completionof reaction. The reaction mixture was concentrated in vacuum and THF (5 mL) was added to theresidue. To the stirred mixture was added NaH (40 mg, 1 mmol) in portions at room temperature. Afteraddition, the mixture was stirred at room temperature for 5 h and TLC showed reaction was complete.Then NH4Cl solution (0.2 mL, concentrated solution) was added and the mixture was concentrated invacuum.The residue was recrystallized fromn-hexane and ethyl acetate to give 24zc as a brown solid(174 mg, 76.0% yield). 1H-NMR: 11.84 (s, 1H), 10.45-10.39 (m, 1H), 8.47 (s, 3H), 8.02 (s, 2H), 7.41-7.39(m, 3H), 7.28-7.26 (m, 3H), 7.23-7.19 (m, 2H), 4.90 (m, 1H), 4.34-4.28 (qd, J = 7.2 Hz, 2H), 3.92-3.89(m, 2H), 3.68-3.59 (m, 2H), 3.40-3.38 (m, 2H), 3.17-3.07 (m, 2H), 1.33-1.30 (t, J = 7.2 Hz, 3H). ESI-MS(m/z) = 695.17 [M + Na]+ |
76% | 27 mg, 0.34 mmol) of Intermediate 27a was added to 4 mL THF and stirred.Add <strong>[14869-41-1]2-(2-chloro-ethoxy)acetic acid</strong> (48 mg, 0.34 mmol) and EEDQ (100 mg, 0.41 mmol), react at 60 ° C for 4 hours, spin dry and add 5 mL of THF.NaH (40 mg, 1 mmol) was added portionwise with stirring, and reacted at room temperature for 5 hours.Add 0.2mL ammonium chloride solution, spin dry,The crude product was recrystallized from n-hexane andEtOAc to afford Intermediate 28z(174 mg, yield 76.0percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With phenylboronic acid; In toluene; at 110 - 111℃;Dean-Stark; Reflux; | 90 ml toluene, lO.OOg <strong>[14869-41-1]2-<strong>[14869-41-1](2-chloroethoxy)acetic acid</strong></strong> (X) oily extract obtained from one of the previous examples, 8.3 Ig 4-nitro-aniine and l .84g phenyl -boronic acid are measured into a 125 ml volume sulfonating flask equipped with a Dean-Stark attachment, a condenser and thermometer. The mixture is heated to the reflux temperature (1 10- 1 11 C), the reaction is checked by a TLC method. After the end of the reaction the mixture is cooled back, 1.00 ml ethylene-glycol is added. Then the mixture is heated again to the temperature of reflux, then it is refluxed for another half an hour. Then the mixture is cooled to a temperature of 0-5C. The suspension is filtered and washed with toluene. The filtrate is dried to a constant mass. The mass of the obtained pastel yellow powder: 12.98g, yield: 83% |
A260973 [83881-47-4]
Methyl 2-(2-chloroethoxy)acetate
Similarity: 0.91
A149345 [17229-14-0]
Ethyl 2-(2-chloroethoxy)acetate
Similarity: 0.88