Structure of 20511-12-0
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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. : | 20511-12-0 |
Formula : | C5H5IN2 |
M.W : | 220.01 |
SMILES Code : | C1=C(C=NC(=C1)N)I |
MDL No. : | MFCD00160312 |
InChI Key : | IVILGUFRMDBUEQ-UHFFFAOYSA-N |
Pubchem ID : | 88579 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.37 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.58 |
Solubility | 0.573 mg/ml ; 0.0026 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.73 |
Solubility | 4.12 mg/ml ; 0.0187 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.62 |
Solubility | 0.524 mg/ml ; 0.00238 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 |
-6.71 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) |
2.21 |
* 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 |
---|---|---|
31% | With copper; In methanol; at 160℃; | 2-Amino-5-methoxy-pyridine. A mixture OF 2-AMINO-5-IODO-PYRIDINE (1 g, 4.54 mmol) in 20 mL of absolute methanol with 400 mg of copper powder and sodium methoxide (6 mmol) was heated at 160 °C overnight in a seal tube. The reaction mixture was cooled to room temperature, diluted with 80 mL of methanol and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by chromatography (80percent ethyl acetate/hexane) to give the title compound (174 mg, 31percent). 1H NMR (CDCl3) : 7.78 (d, J = 2.7, 1H), 7.09 (dd, J = 3.0, 9.0, 1H), 6.48 (d, J= 9.0, 1H), 3.78 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium methylate; In methanol; | A. 2-Amino-5-methoxypyridine is prepared by combining 55 g. of 2-amino-5-iodopyridine, 20 g. of sodium methoxide, 5 g. of copper powder, 500 ml. of methanol in a glass lined bomb and rocking at 150° C. for 12 hours. Upon concentration to dryness, an extraction with chloroform extracts are dried and evaporated to dryness in vacuo. The residue is chromatographed on 1200 g. of silica gel eluding with 50percent ethylacetate and methylenechloride affording 2-amino-5-methoxy pyridine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium; sodium t-butanolate;copper(l) iodide; 2.9-dimethyl-1,10-phenanthroline; In toluene; at 110℃; for 24h;Inert atmosphere; Sealed tube; Sonographic reaction; | Preparation 14-(6-Amino-pyridin-3-ylsulfanyl)-piperidine-1-carboxylic acid tert-butyl esterAdd dry toluene (6.06 mL) to a mixture of 2,9-dimethyl-1,10-phenanthroline (76.52 mg), copper(I) iodide (69.27 mg), sodium tert-butoxide (475.59 mg), 4-mercapto-piperidine-1-carboxylic acid tert-butyl ester (583.5 mg), magnesium (49.10 mg) and 2-amino-5-iodopyridine (550 mg). Bubble nitrogen into the mixture with ultrasound and stir the suspension at 110 C. in a sealed tube for 24 h. Cool and filter through celite. Wash with toluene and remove the solvent under vacuum. Add hexane/EA (1/1) and filter through a celite/silica gel pad, washing twice with hexane/EA (1/1) and then EA. Remove the solvent under vacuum. Purify by silica gel column chromatography eluting with hexane/EA (50-75%) to afford 630 mg of the title compound. MS (ES+): m/z=310 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium phosphate; copper(l) iodide; In 1,4-dioxane; at 110℃; | A solution of Example 149a (200 mg, 0.90 mmol), Example 149b (95 mg, 0.91 mmol), Example 149c (26 mg, 0.18 mmol), CuI (18 mg, 0.09 mmol) and K3PO4 (380 mg, 1.82 mmol) in 1,4- dioxane (5 mL) was stirred at 110oC overnight. The reaction was diluted with CH3CN (5 mL), filtered and concentrated to give the crude product Example 149d (210 mg, quant.) as black oil.1H NMR (400 MHz, DMSO-d6) d 7.85 (br, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 8.0 Hz, 1H), 5.98 (s, 2H), 4.13 (s, 2H), 3.91 (t, J = 4.0 Hz, 2H), 3.61 (t, J = 4.0 Hz, 2H). |
With potassium phosphate;copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 110℃; for 23h; | To a suspension of 5-iodopyridin-2-amine (800 mg) in dioxane (6 mL) were added copper (I) iodide (6.9 mg), trans-cyclohexane-1,2-diamine (44 μL), <strong>[109-11-5]morpholin-3-one</strong> (441 mg), and powdery tripotassium phosphate (1.54 g). The resulting reaction mixture was heated and stirred at 110C for 23 hours. After cooling to room temperature, the reaction mixture was filtered through celite, and the solid was washed with CHCl3. The liquid was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (CHCl3/MeOH = from 100/0 to 88/12) to obtain 4-(6-aminopyridin-3-yl)<strong>[109-11-5]morpholin-3-one</strong> (548.3 mg) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; for 2h; | Step 1:A solution of DIPEA (1.2 mL, 7.0 mmol), A17a (Aldrich, 530 mg, 3.5 mmol) and Ala (300 mg, 2.3 mmol) in DMF (14 mL) is treated with HATU (1.3 g, 3.5 mmol). The mixture is stirred for 2 h and then is diluted with water and EtOAc. The organic layer is separated, washed with water (2 x) and passed through a phase separator. The filtrate is evaporated to dryness and the residue is purified by Combif lash to give A17b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; potassium carbonate; In dimethyl sulfoxide; at 100℃;Inert atmosphere; | 5-iodopyridin-2-amine (200 mg, 0.91 mmol), sodium methyl sulfinate (186 mg, 1.82 mmol) and potassium carbonate (125 mg, 0.91 mmol) was suspended in dimethyl sulfoxide (10 mL). Copper(I)iodide (35 mg, 0.18 mmol) and N,N,N′,N′- tetramethylethylenediamine (53 mg, 0.46 mmol) was added to the suspension and stirred at 100C under nitrogen overnight. The mixture was cooled, diluted with water and ethyl acetate. The biphasic mixture was passed through a celite bed. The organic layer was separated and washed with water, brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with silica gel chromatography eluting with ethyl acetate to yield 5-(methylsulfonyl)pyridin-2-amine (130 mg, 83%) as a solid. |