Structure of 338990-31-1
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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. : | 338990-31-1 |
Formula : | C18H26ClN3O6 |
M.W : | 415.87 |
SMILES Code : | O=C(OCC1=CC=CN=C1N(C(OC(Cl)C)=O)C)CN(C(OC(C)(C)C)=O)C |
MDL No. : | MFCD30184953 |
InChI Key : | KXWGVTDANRDXRN-UHFFFAOYSA-N |
Pubchem ID : | 11281469 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 28 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.56 |
Num. rotatable bonds | 12 |
Num. H-bond acceptors | 7.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 103.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
98.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.42 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.45 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.47 |
Solubility | 0.142 mg/ml ; 0.000341 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.39 |
Solubility | 0.0171 mg/ml ; 0.0000412 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.52 |
Solubility | 0.126 mg/ml ; 0.000302 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) |
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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.94 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
1.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.98 |
* 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 |
---|---|---|
88.4% | With sodium iodide; In acetonitrile; at 45 - 50℃; for 15h; | [N-methyl-N-3-((tert-butoxycarbonylmethylamino)acetoxymethyl)pyridin-2-yl]carbamic acid 1-chloro-ethyl ester(q) (55 g, 0.132 mol, 1.4 eq) and the azole compound of Example 5a) (41.2 g, 0.0944 mol) was dissolved in CH3CN(350 mL) and warmed to 45-50 C. To the solution was added NaI(19.7 g, 0.131 mol, 1.4 eq) and stirred for 15 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The obtained residue was purified by silicagel columnchromatography((eluent: fromAcOEt to AcOEt/MeOH (10/1,v/v) gradient) to give the product as its iodide form(78.7 g, 88.4% yield). [00418] The iodide (66.5 g, 0.07 mol) was dissolved in MeOH(300 mL) and distilled water(200 mL) at 0 C. and strong anion exchange resin[Dia Ion SA10A(200 g)]was added to the solution. The mixture was stirred using an evaporator. After 1 h, the mixture was filtered, washed with methanol and the filtrate was evaporated. The obtained residue was diluted with water(200 mL), brine(200 mL) and ethyl acetate(500 mL). The organic layer was extracted with ethyl acetate and combined ethyl acetate layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silicagel column chromatography((eluent:DCM/MeOH(10/1, v/v)) to give the product (52.1 g, 86.7% yield). |
83% | With sodium iodide; In acetonitrile; at 50 - 60℃; for 12h;Inert atmosphere; | Adding a compound of formula 1 (50 g) to a 500 ml single-mouth round bottom reaction flask,Compound of formula 2 (67 g), NaI (24 g) and anhydrous MeCN (250 ml),Nitrogen replacement, nitrogen protection; heating to 60 C oil temperature, internal temperature 50 C,Stirring for 12 hours; cooling to below 20 C, filtering, filter cake washed with EA;EA (200 ml) and purified water (500 ml) were added to the filtrate, and the mixture was stirred and extracted;Separate, the upper EA phase is wine red; the lower aqueous phase is extracted twice with EA (50 ml).The organic phases were combined and washed with aq. NaCI (50 mL).Dryed by adding 20 g of anhydrous sodium sulfate and concentrated under reduced pressure to give a foamy solid.Used directly in the next reaction;The yield was 83% and the HPLC purity was >90%. |
With potassium iodide; In acetonitrile; at 47 - 50℃; | <strong>[241479-67-4]Isavuconazole</strong> (20 g) and [N-methyl-N-3((tert-butoxycarbonylmethylamino)acetoxy methyl)pyridine-2-yl]carbamic acid 1 -chloro-ethyl ester (24.7 g) were dissolved in acetonitrile (200ml). The reaction mixture was stirred to add potassium iodide (9.9 g). The reaction mixture was stirred at 47-50C for 10-13 hour. The reaction mixture was cooled to room temperature. The reaction mass was filtered through celite bed and washed acetonitrile. Residue was concentrated under reduced pressure to give the crude solid product (47.7 g). The crude product was purified by column chromatography to get its pure iodide form (36.5 g). Yield: 84.5 % HPLC Purity: 87% Mass: m/z 817.4 (M-I)+ |
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