Structure of 10167-97-2
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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. : | 10167-97-2 |
Formula : | C6H8N2O |
M.W : | 124.14 |
SMILES Code : | NC1=NC=C(C=C1)OC |
MDL No. : | MFCD07374873 |
InChI Key : | XJKJHILCYUUVSJ-UHFFFAOYSA-N |
Pubchem ID : | 11320934 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.34 |
Solubility | 5.68 mg/ml ; 0.0458 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.06 |
Solubility | 10.8 mg/ml ; 0.087 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.75 |
Solubility | 2.21 mg/ml ; 0.0178 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 |
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 |
-6.72 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 |
1.0 |
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) |
1.68 |
* 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 |
---|---|---|
51.8% | With sulfuric acid; at 90 - 93℃; for 24h; | 95 percent H2SO4 (10 mL) was stirred at 80 °C, compound 5 (5 mmol, 0.62 g) was added dropwise to the stirred solution keeping the temperature at 80-85 °C. After the addition, stirring was continued at 90-93 °C for about 24 h until 5 can not be detected by TLC. The reaction mixture was poured into crash ice (100 g) and the solution was adjusted to pH 7-8 by gradual addition of Na2CO3. The resulting mixture was extracted several times with diethyl ether (Scheme-I). The combined organic phases were dried with anhydrous Na2SO4 and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (gradient elution: CH3OH/CH2Cl2 = 1:9) to give taupe solid 6 (0.29 g, yield = 51.8 percent). 1H NMR (400 Hz, DMSO-d6), delta (ppm): 5.200 (br, 2H, NH2), 6.327-6.350 (t, 1H, pyr-H), 6.893-6.923 (dd, 1H, pyr-H), 7.497-7.506 (dd, 1H, pyr-H), 8.636 (s, 1H, OH). 13C NMR (100 MHz, DMSO-d6), delta (ppm): 110.00, 128.16, 131.65, 145.25, 150.04. |
44% | A solution of compound 119 in a 48percent aqueous HBr solution was refluxed overnight. The reaction mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (dichloromethane / methanol (7M NH3) 9:1) to give 6-amino-pyridin-3-ol (120) (6.9 g, yield = 44percent) as dark brown crystals. 1H NMR (delta, DMSO-D6): 5.19 (2H, s), 6.33 (IH, d, J = 8.7 Hz), 6.90 (IH, dd, J = 8.7, 3.0 Hz), 7.50 (IH, d, J = 3.0 Hz), 8.61 (IH, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | 4-(6-methoxy-H-imidazo[l,2-a]pyridin-2-yl)-N,N-dimethylbenzenamine (L9).; In a 2-necked round bottomed flask equipped with a condenser and under nitrogen flow were introduced the <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> (0.15 g, 1.17 mmol), the 2-bromo-4'- dimethylamino-acetophenone (0.31 g, 1.29 mmol) and 14 mL of absolute EtOH. The reaction mixture was stirred at reflux for 2 h. After it cooled down, NaHCO3 (0.15 g, 1.75 mmol) was added, the mixture was refluxed for another 6 hrs. After the solvent was removed, the residue was dissolved in AcOEt. The organic phase was washed with water, dried over MgSO4, and filtered. The solvent was removed to afford 0.271 g crude product, which was purified by FCC (DCM/ AcOEt = 1:1) to give 0.129 g (yield 41percent) of the product as yellow solid. M.p. = <n="16"/>177-179°C. 1H NMR (270 MHz; CDCl3), delta 7.82 (d, 3JHH = 8.7 Hz, 2H, Ar-H), 7.71 (s, IH, H-3), 7.65 (s, IH, Ar-H), 7.53 (d, 3JHH = 9.6 Hz, IH, Ar-H), 6.96 (dd, 3JHH = 9.6, 4JHH = 1.8, IH, Ar-H), 6.81 (d, 3JHH = 8.8, 2H, Ar-H), 3.84 (s, 3H, OCH3), 3.02 (s, 6H, NCH3); 13C(1H) NMR (125 MHz, CDCl3), delta 151.0, 150.4, 149.2, 146.0, 143.0, 126.8 (Ph-2,6), 119.2 (C7), 117.0 (C8), 112.5 (Ph-3,5), 107.6 (C3), 106.2 (C5), 56.2 (OCH3), 40.5 (NCH3). m/z (EI-MS): 267 (At), 252 (M+-CH3); CaIc. C16HnN3O: C, 71.89; H, 6.41; N, 15.72. Found: C, 71.60; H, 6.62; N, 15.96. |
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