Structure of 7400-06-8
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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. : | 7400-06-8 |
Formula : | C10H17N3O3 |
M.W : | 227.26 |
SMILES Code : | CCOC(CC1=C(O)N=CN=C1N)OCC |
MDL No. : | MFCD02094191 |
InChI Key : | DLABUHZHXFNKMQ-UHFFFAOYSA-N |
Pubchem ID : | 135408688 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.6 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 59.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
90.49 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.57 |
Solubility | 6.1 mg/ml ; 0.0268 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.18 |
Solubility | 1.51 mg/ml ; 0.00664 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.25 |
Solubility | 1.29 mg/ml ; 0.00569 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) |
Yes |
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 |
-7.19 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 |
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) |
2.67 |
* 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 |
---|---|---|
1.6 g (66%) | With sodium ethanolate; sodium; In ethanol; ethyl acetate; | EXAMPLE 2 SYNTHESIS OF 4-CHLORO-5,7-DIHYDRO-PYRROLO[2,3-D]PYRMIDIN-6-ONE To a solution of 45.2 mmol of sodium ethoxide (made in situ from sodium and absolute ethanol) in 40 mL of absolute ethanol was added formamidine hydrochloride (1.74 g, 21.5 mmol) and <strong>[52133-67-2]2-cyano-4,4-diethoxy-butyric acid ethyl ester</strong> (2.47 g, 11 mmol, literature reference: Davoll, J., J. Chem. Soc. 131-138 (1960)). The mixture was refluxed for 6 hours, cooled to room temperature and filtered. The solid was washed with hot acetonitrile. The filtrate was neutralized with acetic acid to pH 6.5 and then evaporated to half of the volume. Ethyl acetate (50 mL) was added to the resultant filtrate. The precipitate was filtered, washed with EtOAc to give 1.6 g (66percent) of 6-amino-5-(2,2-diethoxy-ethyl)-3H-pyrimidin-4-one as a white solid which was used without further purification. 1H NMR (300 MHz, DMSO-d6)delta 11.46 (s, br, 1H, NH), 7.68 (s, 1H), 6.07 (s, br, 2H, NH2), 4.54 (t, J=6.0 Hz, 1H, CH(OCH2CH3)2), 3.53-5.62 (m, 2H, CH(OCH2CH3)2), 3.31-3.49 (m, 2H, CH(OCH2CH3)2), 2.50 (m, 2H, CH2), and 1.05 (t, J=6.93 Hz, 6H, CH(OCH2CH3)2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7H-Pyrrolo[2,3-d]pyrimidin-4-ol (7).; Formamidine acetate (5, 1.04 Kg,10 mol, 1.25 equiv) was added to 7.52 L of (21percent wt) sodium ethoxide (EtONa) in ethanol (EtOH, 62.5 equiv) and the resulting solution was stirred for 60 minutes. <strong>[52133-67-2]2-cyano-4,4-diethoxy-butyric acid ethyl ester</strong> (4, 1.8 Kg, 8.0 mol) was then added and the resulting reaction mixture was refluxed for seven hours. The stirring was turned off after the solution was cooled and the solids were allowed to settle. The supernatant ethanol solution was removed, leaving the solids in the bottom of the reaction flask. The ethanol was evaporated and the residue was added back to the solids remaining in the reaction flask with water and ice at a ratio of 600 mL/mol. A solution of 6 N aqueous HCl was added to the resulting solution at a ratio of 500 mL/mol at 15° C. The resulting solution was then heated at 45° C. for 45 minutes. The solution was again cooled to 15° C. and the pH was adjusted to 8.0 with the addition of aqueous ammonium hydroxide. The precipitated solids were collected by filtration, washed with water (2.x.225 mL/mol) and pulled dry. The solids were further washed with 1:1 ethyl acetate/heptane (500 mL/mol), then heptane (2.x.250 mL/mol) and dried in vacuum to afford 7H-pyrrolo[2,3-d]pyrimidin-4-ol (7, 738.6g, 1081 g theoretical, 68.3percent) as yellow to brown to yellow crystalline material. For 7: 1H NMR (DMSO-d6, 300 MHz) delta ppm 11.88 (bs, 1H), 11.80 (bs, 1H), 7.81 (s,1H), 7.02 (dd,1H, J=3.2, 2.3 Hz), 6.42 (dd, 1H, J=3.5, 2.3 Hz); C6H5N3O (MW, 135.12), LCMS (EI) m/e 136 (M++H) and (M++Na) m/e 158. |
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