Structure of 1-Bromo-5-chloropentane
CAS No.: 54512-75-3
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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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CAS No. : | 54512-75-3 |
Formula : | C5H10BrCl |
M.W : | 185.49 |
SMILES Code : | ClCCCCCBr |
MDL No. : | MFCD00001016 |
InChI Key : | PHHNNDKXQVKJEP-UHFFFAOYSA-N |
Pubchem ID : | 96070 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.65 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.71 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.4 |
Solubility | 0.746 mg/ml ; 0.00402 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.3 |
Solubility | 0.927 mg/ml ; 0.005 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.37 |
Solubility | 0.0786 mg/ml ; 0.000424 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.55 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 |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.73 |
* 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 |
---|---|---|
99.1% | Step 1. Under dry N2 protection, add 7.3 g of diethyl oxalate, 9.3 g of 1-bromo-5-chloropentane and a four-necked flask equipped with a condenser, a thermometer, a stirrer and a 50 ml constant pressure dropping funnel. a mixture of 30 ml of tetrahydrofuran;Step 2, at -25 ° C,Quickly add 1.0g PSIM-MgBr,During the dropwise addition reaction, the reaction temperature is kept at about -10 ° C, and after the completion of the dropwise addition, the reaction is continued for 1 h;Step 3. Hydrolyze with 15 ml of 4 M hydrochloric acid, and ensure the reaction temperature is below 0 °C during acid hydrolysis. The organic layer was separated, and the aqueous layer was extracted with dichloromethane, and washed with a saturated sodium chloride solution, and shaken with a NaHS03 saturated solution;Step 4: After the shaking is completed, the organic layer and the aqueous layer are neutralized with a saturated NaHC03 solution, and the organic layer is rotated to evaporate the tetrahydrofuran. The organic layer is combined, neutralized with saturated NaHC03, washed with NaHS03, then washed with NaCl until neutral, and evaporated.Evaporation under reduced pressure gave ethyl 7-chloro-2-oxoheptanoate. | |
90% | (Example 1) Example 1 was carried out in a reaction apparatus 10 shown in Figure 1. A main flow channel 12 is a circular pipe made from stainless steel, and introduction points 12o and 12p are 180-degree T-shaped mixture flow channels made from stainless steel. A Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. The reagent 1-bromomagnesium-5-chloropentane was prepared by adding a magnesium powder to 1-bromo-5-chloropentane. Diethyl oxalate (7.4 mol/L) which had not been diluted by the solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel 32, at 110 mL/min and 5.1 mL/min, respectively. Used pumps 20 and 26 were a smooth flow pump made by TACMINA CORPORATION. From the above described conditions, a mixed solution of these materials stays in the flowing-type fine reaction flow channel 32 for approximately 14 seconds. The Grignard reagent and diethyl oxalate were accommodated in a supply container and controlled at 10°C and room temperature respectively, and a thermostatic liquid tank 28 accommodated methanol as a refrigerant 30 and was controlled at -15°C. The produced liquid was collected and quenched with a dilute hydrochloric acid. The target substance of ethyl-7-chloro-2-oxalic pentane was obtained in the yield of 90percent. | |
l-bromo-5-chloropentane (29 lg, 1.57 mol) was reacted with diethyl oxalate (206.5g) through Grignard reaction to obtain ethyl 7-chloro-2-oxo-heptanoate (3) and the compound (3) was reacted with (S)-2,2-dimethylcyclopropanecarboxamide to obtain ethyl (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptanoate (237g, 0.79 mol). The above-described step was performed by the procedure according to the procedure disclosed in EP 48301 (Bl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrosylsulfuric acid; sulfuric acid; In water; toluene; | Then, 230 g (0.62 mol) of the crude product of ethyl 7-chloro-2-(1-oxoethyl)heptanoate thus obtained was cooled to 5°C, to which 228 g (0.81 mol) of 44percent nitrosylsulfuric acid/sulfuric acid solution was added dropwise over 6 hours, and the mixture was further stirred at the same temperature for 4 hours. In another flask, 113 g (1.39 mol) of 37percent aqueous formalin solution and 291 g of toluene were placed and then cooled to 10°C, to which the above reaction solution was added dropwise at the same temperature over 2 hours, and the mixture was further stirred at the same temperature for 30 minutes. The reaction mixture was subjected to phase separation, and the oil layer was washed with 107 g of 5percent aqueous sodium carbonate solution and then with 107 g of water to give 508 g of a toluene solution containing <strong>[78834-75-0]ethyl 7-chloro-2-oxoheptanoate</strong>. In the toluene solution, 18.1percent by weight (72percent yield) of <strong>[78834-75-0]ethyl 7-chloro-2-oxoheptanoate</strong> and 5.4percent by weight of 1-bromo-5-chloropentane were contained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | Compound 2 (518g, 1.88mol) was dissolved in 3.5L DMF necked flask fitted with a solvent, was added cesium carbonate (797.4g, 2.45mol), was added compound 3 (364.7g, 1.98mol), N2 protected, stirred at room temperature overnight.TLC showed disappearance of compound 2.The reaction solution was slowly added to 4L of ice water, extracted with ethyl acetate, the combined organic phases, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 711g of compound 4 as a yellow oil (yield: 100 %), the next step without further purification. |