Structure of 2078-71-9
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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. : | 2078-71-9 |
Formula : | C3H8N2O2 |
M.W : | 104.11 |
SMILES Code : | O=C(N)NCCO |
MDL No. : | MFCD00059080 |
InChI Key : | CLAHOZSYMRNIPY-UHFFFAOYSA-N |
Pubchem ID : | 73984 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 23.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
75.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.29 |
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 |
-1.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.8 |
Solubility | 651.0 mg/ml ; 6.25 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.65 |
Solubility | 466.0 mg/ml ; 4.48 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.32 |
Solubility | 216.0 mg/ml ; 2.07 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 |
-8.16 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 |
0.0 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) |
1.02 |
* 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 |
---|---|---|
59.4% | With sodium; In ethanol;Cooling with ice; Reflux; | Synthesis of 1-hydroxy-ethyl-6-aminouracil (compound 1) Metal sodium (2.8 g, 120 mmol) was added carefully in 90 mL of ethanol anhydride in a 200 mL mad apple-type flask with a stirrer coated with fluoropolymer in ice bath with constant stirring and was completely dissolved. Then, 6.3 g (60 mmol) of hydroxyethylurea and 6.4 mL (60 mmol) of ethylcyanoacetate were added and refluxed for seven hr. The obtained solution was filtrated, washed with ethanol, solubilized in water, neutralized with 1.0 M diluted hydrochloric acid, filtrated and provided white pellets, which were recrystallized in water and gave compound 1 as a white crystal (6.1 g, 35.6 mmol, yield: 59.4percent); 1H NMR (DMSO-d6, 400 MHz): delta 3.54 (t, 2H, NCH2CH2, 9.6 Hz), 3.83 (t, 2H, CH2OH, 9.6 Hz), 4.57 (br, 1H, CHCNH2), 5.09 (br, 1H, OH), 6.61 (br, 2H, NH2), 10.32 (br, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): delta 44.13 (NaC2CH2), 59.28 (CH2OH), 76.52 (CHCNH2), 151.87, 157.04, 162.89. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Among the compounds of formula (I), mention may be made especially of the following preferred compounds:urea...isobutylureatert-butylureacyclopentylurea1-ethoxyurea2-hydroxyethylureaN-(2-hydroxypropyl)ureaN-(3-hydroxypropyl)ureaN-(2-dimethylaminopropyl)urea... | ||
Among the compounds of formula (I), mention may be made especially of the following particularly preferred compounds:ureamethylureaethylureapropylurea1-ethoxyurea2-hydroxyethylureaN-(2-hydroxypropyl)ureaN-(3-hydroxypropyl)ureaN-(2-dimethylaminopropyl)ureaN-(3-dimethylaminopropyl)urea... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In anhydrous DMF-THF; | EXAMPLE 5 Preparation of 2-(tetrafluoroethoxy)ethylurea. According to the modalities already described in example 1, 4.8 l of tetrafluoroethylene were absorbed in the reaction mixture consisting of 2-hydroxyethyl-urea (20.6 g), prepared from ethanolamine according to known methods, and sodium hydride (0.5 g) in 100 ml of anhydrous DMF-THF (1:1). At the end of the reaction one acidified cautiously with concentrated HCl, the solvents were evaporated at reduced pressure and the residue was treated with 150 ml of 1:1 ethyl ether-ethyl acetate. One filtered and the filtrate was evaporated at reduced pressure till a constant weight was reached, thereby obtaining 36 g of 2-(tetrafluoroethoxy)ethylurea as a light yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 3 1-(2,2,2-trichloro-1-hydroxyethyl)-3-[2-(2,2,2-trichloro-1-hydroxyethoxy)-ethyl]urea 52 g (0.5 mole) of monoethanolurea was heated to 80° C.; 149.0 g (1.01 mole) of chloral was added dropwise thereto between 80°-90° C. with stirring and heated between 80°-90° C. for an additional hour. On cooling, a clear viscous liquid product was obtained that weighed 200 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formaldehyd; sulfuric acid; In water; | EXAMPLE 1 Preparation of 1,1'-Methylenebis(2-hydroxyethyl)Urea STR8 A mixture of 450 parts of 2-hydroxyethylurea, 230 parts of water, and 2.3 parts of concentrated sulfuric acid is stirred and heated to 50° C. to effect solution. Heating is then discontinued and 174.3 parts of 37.2percent formaldehyde in water is added to the solution over a period of 20 minutes. The reaction mixture is cooled to room temperature, and the resulting white precipitate is collected by filtration and recrystallized twice from methanol to obtain a product which melts at 164°-165° C. Calculated for C7 H16 N4 O4: C,38.18percent; H,7.32percent; N,25.44percent. Found: C,38.02percent; H,7.28percent; N,24.96percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | EXAMPLE 2 Preparation of AES from 2-aminoethyl carbamate. The procedure of Example 1 was repeated except that the desired quantity of ammonium bisulfate is charged to a 250 ml three-necked round bottom flask equipped with a large egg shaped stirrer. The desired quantity of the appropriate solvent (see Table 2) is then added to the flask, and the flask is fitted with a Dean-Stark receiver and a water-cooled condenser. A thermometer is fitted to the central neck of the reaction flask, and an addition funnel is placed in the remaining neck of the flask. The desired quantity of 2-aminoethylcarbamate (prepared according to the procedure of W. F. Tousignant and A. W. Baker, J. Org. Chem., 22, 166 (1957) from urea and ethylene oxide; a 2-aminoethylcarbamate product, mixed with approximately 10-15 weight percent of the isomeric 2-hydroxyethyl urea, is obtained.) The resulting product is dissolved in water to provide a solution containing 33percent 2-aminoethylcarbamate by weight. The solution is placed in the addition funnel. The mixture of organic solvent and ammonium bisulfate is heated to reflux temperature with stirring, and the solution of 2-aminoethycarbamate added carefully to prevent bumping. Upon completion of the addition, the addition funnel is removed from the reaction flask, and replaced with a ground glass stopper. Samples were removed from the reaction mixture at the times indicated in Table 2 for each example. Analyses were carried out by 200 MHz proton nmr on an IBM SY-200 FT NMR and by carbon-13 nmr on a Bruker WP-200 FT NMR Spectrometer. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In DMF-THF; | EXAMPLE 5 Preparation of 2-tetrafluoroethoxy)ethylurea According to the procedures already described in Example 1, 4.8 l of tetrafluoroethylene were absorbed in the reaction mixture consisting of 2-hydroxyethyl-urea (20.6 g), prepared from ethanolamine according to known methods, and sodium hydride (0.5 g) in 100 ml of anhydrous DMF-THF (1:1). At the end of the reaction, one cautiously acidified the resulting reaction mixture with concentrated HCl, the solvents were evaporated at reduced pressure, and the residue was treated with 150 ml of 1:1 ethyl ether-ethyl acetate. This was then filtered and the filtrate evaporated at reduced pressure till a constant weight was reached, thereby obtaining 36 g of 2-(tetrafluoroethoxy)ethylurea as a light yellow liquid. |
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