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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
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Structure of 4457-32-3
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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.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 4457-32-3 |
Formula : | C8H6ClNO4 |
M.W : | 215.59 |
SMILES Code : | O=C(Cl)OCC1=CC=C([N+]([O-])=O)C=C1 |
MDL No. : | MFCD00007375 |
InChI Key : | MHSGOABISYIYKP-UHFFFAOYSA-N |
Pubchem ID : | 78205 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.51 |
TPSA ? Topological Polar Surface Area: Calculated from |
72.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.79 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.89 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.99 |
Solubility | 0.222 mg/ml ; 0.00103 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.96 |
Solubility | 0.0236 mg/ml ; 0.000109 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.5 |
Solubility | 0.69 mg/ml ; 0.0032 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
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 |
-5.63 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 |
3.0 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) |
1.71 |
* 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 |
---|---|---|
93% | Example 4: Synthesis of (4R,5S,6S)- 3-[[(3S,5S)-5-[(dimethylamino)carbonyl]-3-ρyrrolidinyl]thio]-6-[(lR)-l-hydroxyethyl]-4-methyl- 7-oxo-l-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid (I)Synthesis of (2S,4S)-2-dimethylaminocarbonyl -4-thio-l-PNZ-pyrrolindine (XX)L-hydoxyproline (XXVI) (26.2 g, 0.20 mol) was added to a solution of sodium hydroxide (220 ml, 2N) and cooled to O0C to 50C. The solution of p-nitrobenzyl chloroformate dissolved in <n="17"/>methylene chloride (40 ml) was added dropwise. After stirred at the same temperature for 1 h, the phase of methylene chloride was separated. The aqueous phase was washed with methylene chloride (70 ml) and acidified with concentrated sulfuric acid (36.6 g) at a temperature of O0C to 5 C . Substantive crystals were precipitated, collected by filtration under vacuum, washed with water, dried, and afford trans- l-(p-nitrobenzyloxycarbonyl) -4-hydroxyl-L-proline (XXV) (57.8 g, yield 93%), m.p.: 134~135.5C. | |
93% | Example 6] Synthesis of (2S,4S)-2-dimethylaminocarbonyl -4-acetylthio-l-PNZ-pyrrolidine (XIX)1. Synthesis of trans- l-(p-nitrobenzyloxycarbonyl) -4-hydroxyl-L-proline (XV) L-hydoxyproline (XXVI) (26.2 g, 0.20 mol) was added to a solution of sodium hydroxide(220 ml, 2N) and cooled to 0C to 5C. The solution, of p-nitrobenzyl chloroformate dissolved in methylene chloride (40 ml) was added dropwise. After stirred at the same temperature for 1 h, the phase of methylene chloride was separated. The aqueous phase was washed with methylene chloride (70 ml) and acidified with concentrated sulfuric acid (36.6 g) at a temperature of 0C to 5 C . Substantive crystals were precipitated, collected by filtration under vacuum, washed with water, dried, and afford trans- l-(p-nitrobenzyloxycarbonyl) -4-hydroxyl-L-proline (XXV) (57.8 g, yield 93%), m.p.: 134~135.5C. | |
92.6% | With sodium hydroxide; In dichloromethane; water monomer; at 0 - 5℃; for 3h; | Add sodium hydroxide (66.9g, 1.68mol) and 600g of water to the reaction flask, after stirring and dissolving, add trans-L-hydroxyproline (100g, 0.76mol), stir and dissolve completely and then cool down to 0C, Add dropwise a solution of 50% p-nitrobenzyl chloroformate in dichloromethane (370 g, 0.86 mol), the temperature does not exceed 5 C; after the dropping is completed, the reaction is carried out at 0 to 5 C for 3 hours. The phases were extracted with 100 mL of dichloromethane; the aqueous phase was separated, and the pH was adjusted to 2-3 with 10% hydrochloric acid, then extracted three times with ethyl acetate (200 mL×3), and the organic phases were combined, washed with saturated brine, and washed with anhydrous sodium sulfate. It was dried, filtered, concentrated to dryness, and recrystallized with ethanol to obtain 219.2 g of white solid (intermediate 7) with a yield of 92.6%. |
80% | With sodium hydroxide; In water monomer; toluene; at 0 - 20℃; for 2h;Inert atmosphere; Schlenk technique; | trans-4-Hydroxy-L-proline (SI, 1.0 g, 7.6 mmol, 1.0 eq.) was dissolved in aqueous NaOH (0.5 M, 34 mL) and cooled in an ice bath. At 0 - 5 C, 4-nitrobenzoylchloroformate (1.9 g, 8.6 mmol, 1.1 eq.) in toluene (25 mL) was added dropwise. The bi-phasic mixture was stirred for two hours, after which the toluene (30 mL) was added and the phases separated. The aqueous phase was extracted with toluene and the combined organic phases extracted with aqueous NaOH (0.5 M). The aqueous phases were combined, adjusted to pH = 1 by adding cone. HCI and extracted with ethyl acetate (3 times). The extract was dried over sodium sulfate, filtered and concentrated in vacuo. Thus, compound 1 (1.89 g, 6.1 mmol, 80%) was obtained as off-white solid. ESI-LRMS for Ci3Hi5N207+[MH+]: calcd. 311.1 found 311.2 |
Trans-4-hydroxy-L-proline (II) was added to a solution of sodium hydroxide in water at 0-5 C, and stirred to get a clear solution, followed by p- nitrobenzyloxycarbonyl chloride in dichloromethane (MDC) was added and stirred till completion of reaction. at 0-5 C. To this reaction mass sodium hydroxide solution was added and the layers were separated. To the aqueous layer methanol was added and pH was adjusted to acidic using sulphuric acid at 0-5 C. The solid obtained was filtered, washed with water and dried in vacuum at 50C to afford the title compound (III) as colorless crystals. | ||
31.95 kg | With sodium hydroxide; In dichloromethane; water monomer; at 0 - 5℃; for 5h;Large scale; | 20L reactor water 12kg,1kg sodium hydroxide, stirred and dissolved, cooled to 25 ~ 30 ,Add L-hydroxyproline 15kg, stirring to dissolve,Cool to 0 ~ 5 ,The temperature was controlled at 0 ~ 5 2.7kg of p-nitrobenzyl chloroformate and 3kg of dichloromethane were added dropwise.Dropping about 2 hours, dropping is completed,Keep stirring 0 ~ 5 for about 3 hours. Detection reaction is complete.The dichloromethane phase was separated, the aqueous phase was washed with 3 kg of dichloromethane, the aqueous phase was separated,Control temperature but 15 degrees,Concentrated sulfuric acid adjusted to pH 2, cooled to 0 filtration,Washed, dried in the product(5) To a solution of (2S, 4R) -4- hydroxy- 1 - (((4-nitrobenzoyl) oxy) carbonyl) pyrrolidine-31.95kg |
With sodium hydroxide; In water monomer; toluene; at -5 - 0℃; for 1.25h;pH 9.0; | In a 500mL three-neck bottle added purified water 192g, add 15.3g of sodium hydroxide, stir and dissolve, and cool at 0 C; add 3g of 3-hydroxyproline, stir and dissolve; cool down at -5 C, added the drops of about 180g of p-nitrobenzyl chloroformate toluene solution, after about 1 hour, the drop is completed and pΗ=9; continue to stir for 15 minutes, and then let stand for 20 min, dispense, and obtained lower aqueous phase; in the lower aqueous phase added toluene 63mL X 3 and wash three times, stand still; control the internal temperature at 10 C, and add 6N hydrochloric acid to the aqueous phase, add dropwise until the water phase becomes turbid and stop adding, pH=4, add a small amount of seed crystals and stir until more crystals are precipitated, continue to add hydrochloric acid at pΗ = 2 (a total of about 5g of 6N dilute hydrochloric acid is required), cool down at 0 C, heat 1h suction filtration, wash with pure water to pΗ = 3, obtained compound I hydrate product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoroacetic acid; In dichloromethane; | Step A 4-(N-((4-Nitrobenzyl)oxycarbonyl)-N-(prop-1-yl)amino)-piperidine trifluoroacetate The title compound was prepared by the reaction of <strong>[301225-58-1]4-(N-(prop-1-yl)amino)-1-tert-butoxycarbonylpiperidine</strong> (from Example 17, Step A) with (4-nitrobenzyl)chloroformate, followed by treatment of the product with 50% TFA in CH2Cl2 to remove the tert-butoxycarbonyl group, affording the title compound. ESI-MS: 322.2 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With pyridine; triethylamine; In dichloromethane; | (1) 4-Hydroxy-1-(p-nitrobenzyloxycarbonyl)piperidine To a solution of <strong>[5382-17-2]4-hydroxypiperidine hydrochloride</strong> (3.0 g, 21.8 mmol) in a mixture of methylene chloride (90 ml) and pyridine (15 ml) were added chloroformic acid p-nitrobenzyl ester (15.4 g, 72.0 mmol) and triethylamine (13.1 ml, 93.8 mmol) in an ice bath. The mixture was stirred at room temperature for 3 days. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane: ethyl acetate (1: 1) --> ethyl acetate as the eluant to afford 4-hydroxy-1-(p-nitrobenzyloxycarbonyl)piperidine (2.96 g, yield 48percent) as pale yellow crystals. 1H-NMR (400 MHz, CDCl3): delta (ppm) 8.23 (2H, d, J=8.1Hz), 8.51 (2H, d, J=8.1Hz), 5.23 (2H, s), 3.98 - 3.87 (3H, m), 3.30 - 3.15 (2H, m), 1.96 - 1.85 (2H, m), 1.59 - 1.48 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a mixture of 56.4 mg (0.4 mmol) ethyl methyl 5-amino-2- furancarboxylate in 5mL of anhydrous dichloromethane was added 84.5 mg (0.42 mmol) 4-nitrobezenechloroformate. The reaction mixture was stirred at room temperature for half an hour and concentrated. Diisopropylethylamine (0.14 mL, 0.8 mmol), DMHB resin bound 0-(1, 1-dimethylethyl)-N-{(3S)-1-[(2- nitrophenyl) sulfonyll-3-pyrrolidinyl}-L-tyrosinamide 4 (200 mg, 0.16 mmol) and dimethyl formamide (5 mL) were added to reaction mixture and shaked overnight.. The resin was washed with CH2CI2 (3 x 1 mL), CH2CI2/MeOH (1: 1, 3 x 1 mL), MeOH (3 x 1 mL) and CH2CI2 (3 x 10mL). |
A756919 [88091-68-3]
4-Nitrophenethyl carbonochloridate
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