Structure of 62037-46-1
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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. : | 62037-46-1 |
Formula : | C3H9Cl2NO |
M.W : | 146.02 |
SMILES Code : | OC(CCl)CN.[H]Cl |
MDL No. : | MFCD01697322 |
InChI Key : | ZCPJBHYNOFIAPJ-UHFFFAOYSA-N |
Pubchem ID : | 147580 |
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 | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 32.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.65 |
Solubility | 32.6 mg/ml ; 0.223 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.58 |
Solubility | 38.0 mg/ml ; 0.26 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.36 |
Solubility | 64.3 mg/ml ; 0.441 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 |
-7.15 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) |
2.0 |
* 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 |
---|---|---|
EXAMPLE 5 (+-)-1-Amino-3-chloro-2-propanol hydrochloride (+-)-(V) A slurry of (+-)-1-phthalimido-3-chloro-2-propanol (IVC, 40.018 g, 166.98 mmol) in hydrochloric acid (37.5 wt %, 79 ml, 968 mmol, 5.80 eq) and water (82 ml) is stirred at 109 for 5 hrs. The mixture is cooled to 22 and the precipitate is removed by filtration with reduced pressure and washed with water (40 ml). The filtrate is concentrated under reduced pressure to 26 g net weight and ethanol (100 ml) added. The mixture is warmed to 75 to give a solution then cooled to -12 and the resultant precipitate collected by filtration with reduced pressure, washed with ethanol cooled to -12 and dried to give the title compound, mp=101-104; NMR (CD3 OD) 2.96, 3.21, 3.57-3.64 and 4.03-4.09 delta; CMR (CD3 OD) 43.54, 46.95 and 68.71 delta; MS (CI, NH3), M/Z (relative intensity) 129 (12), 127 (39), 112 (56), 110 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dipotassium hydrogenphosphate; In tetrahydrofuran; water; at 0 - 20℃; | A three-necked flask was charged with <strong>[62037-46-1]1-amino-3-chloropropyl-2-ol hydrochloride</strong> (14.60 g, 100 mmol) and tetrahydrofuran(73 mL), water (73 mL), stirred and cooled to 0 to 5 C, added with dipotassium hydrogen phosphate (34.84 g, 200 mmol), stirred for 5 minAfter the clockwise drop of ethyl sulfonyl chloride (13.50g, 105mm0l), plus the temperature after warming to room temperature for 3-4 hours, the end of the reaction0.5mol / L dilute hydrochloric acid 73mL quenching reaction, stirring and dispensing, water and then extracted with ethyl acetate 35mL 2 times, combined organic saturatedAnd washed with salt (73 mL), dried over anhydrous sodium sulfate and concentrated to give N-(3-chloro-2-hydroxypropyl) ethane sulfonamide Followed by the next step (GC purity of about 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.71% | With sodium hydrogencarbonate; In methanol; water; at 20℃; for 3h; | The reaction flask was charged with 116.8 g of compound II (0.80 mol)191.8 g of Boc2O (0.88 mol) and 1500 ml of methanol, stirred,And 1200 ml of an aqueous solution containing 80.6 g of sodium hydrogencarbonate (0.96 mol)And then reacted at room temperature for 3 hours. After the reaction was complete, the methanol was removed by concentration,The residue was extracted with 2000 ml of methylene chloride and the dichloromethane layer was washed with water,And finally dried over anhydrous sodium sulfate; filtered, the filtrate was concentrated to dryness,174.3 g of an oil was obtained, and 1200 ml of petroleum ether was added to the oil to freeze the crystals,The filter cake was washed with petroleum ether to give 161.7 g of the white solid, compound III; mp 48-51 C, molar yield: 96.71% (calculated as compound II). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.04% | The reaction flask was charged with 1200 ml of ethanol and 111.3 g of benzaldehyde (1.05 mol)110 ml of 25% aqueous ammonia (1.60 mol) was added, and after stirring for 15 minutes, 92 g of epichlorohydrin (1.00 mol)The control temperature was lower than 40 C, the addition was completed, reacted at 35-40 C for 8 hours, and then reacted at room temperature for 15 hours,After vapor phase detection of epichlorohydrin almost completely disappeared, the reaction solution was concentrated to remove about 1/3 volume of ethanol,Then, 800 ml of toluene was added, and the mixture was stirred at a temperature of 35 to 40 C and 270 ml of 6N hydrochloric acid (1.62 mol)After completion of the dropwise addition, the reaction was continued for 6 hours at this temperature, and after the completion of the reaction,The upper layer was washed with water, the aqueous layers were combined, concentrated to dryness, and the residue was concentrated by adding absolute ethanol,Finally, toluene was added to concentrate to remove the contained water, and the resulting residue was recrystallized from ethanol and ethyl acetate,To give 108.1 g of a white solid, compound II; mp: 127-130 C, molar yield: 74.04% (calculated as epichlorohydrin). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
172.2 mg | With pyridine; In dichloromethane; at 0 - 23℃;Inert atmosphere; | To a suspension of <strong>[62037-46-1]1-amino-3-chloropropan-2-ol hydrochloride</strong> (175.2 mg, 1.2 mmol, 1.0 eq) and pyridine (0.49 mL, 6.0 mmol, 5.0 eq) in DCM (3 mL) at 0 C was added the crude acid chloride 16 from the above reaction. The reaction mixture was allowed to warm to 23 C over 2 h, and then stirred overnight at rt. The resultant mixture was partitioned between DCM (3 mL) and water (5 mL). The organic layer was washed with saturated NaHCO3 (aq, 5 mL) and brine (5 mL), dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude material was purified by column chromatography on silica gel, using a mobile phase gradient of 15 to 40% of EtOAc/hexanes to yield the acrylamide 17 (172.2 mg, 0.49 mmol, 41% from 15) as a white solid. 1H NMR (500 MHz, DMSO-d6) delta 7.44 - 7.39 (m, 4H), 7.37 (t, J= 5.6 Hz, 1H), 7.24 (d, J= 8.6 Hz, 2H), 7.21 - 7.17 (m, 2H), 6.99 (d, J= 8.7 Hz, 2H), 5.35 (d, J= 5.3 Hz, 1H), 3.83 - 3.74 (m, 1H), 3.58 (dd, J= 11.2, 4.4 Hz, 1H), 3.47 (dd, J= 11.2, 6.0 Hz, 1H), 3.34 - 3.28 (m, 1H), 3.19 (ddd, J = 13.4, 6.7, 5.6 Hz, 1H); 13C NMR (126 MHz, DMSO-d6) delta 167.32, 137.21, 135.65, 133.96, 132.78, 132.71, 131.30, 129.40, 129.07, 128.27, 128.23, 69.06, 47.88, 43.19; HRMS m/z calcd. for C18H18Cl2NO2 [M+H]+ 350.07091, found 350.06477. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: [0445] Certain compounds disclosed herein with an amide moiety, without a triazole moiety, were synthesized according to the above scheme, over two steps. In the first step, <strong>[62037-46-1]1- amino-3-chloropropan-2-ol hydrochloride</strong> was combined with R-COOH, 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl), hydroxybenzotriazole hydrate (HOBt.H2O), triethylamine (Et3N), and dichloromethane (DCM), and the mixture stirred at room temperature for 18 h. In the second step, the product from the first step was reacted with NaOH (1N) and acetone at room temperature for 30 minutes to produce the final compound comprising an amide moiety, without a triazole. |
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