Structure of 41288-96-4
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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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Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 41288-96-4 |
Formula : | C5H4ClNO |
M.W : | 129.54 |
SMILES Code : | C1=C(C=NC(=C1)Cl)O |
MDL No. : | MFCD00234050 |
InChI Key : | KVCOOWROABTXDJ-UHFFFAOYSA-N |
Pubchem ID : | 819821 |
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 | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.61 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.09 |
Solubility | 1.05 mg/ml ; 0.00808 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.72 |
Solubility | 2.47 mg/ml ; 0.019 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.03 |
Solubility | 1.21 mg/ml ; 0.00938 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 |
-6.08 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 |
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) |
1.43 |
* 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 |
---|---|---|
90% | With dmap; In dimethyl sulfoxide; at 80℃; for 3h; | A mixture of <strong>[13790-39-1]4-chloro-6,7-dimethoxyquinazoline</strong> (0.63 g, 2.80 mmol), 6- chloropyridin-3-oi (0.37 g, 2.84 mol), and DMAP (0.35 g, 2.84 mmol) in DMSO (3 mL) was stirred at 80 C for 3 h. The reaction mixture was then cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated and dried over sodium sulfate. The diying agent was filtered off, and the filtrate concentrated under reduced pressure to give a residue, which was purified by chromatography (ethyl acetate/hexanes = 6/4) to provide 4-((6-chloropyridin-3-yl)oxy)-6,7-dimethoxyquinazoline as a white solid (0.8 g,90%). fH NMR (DMSO-de, 300 MHz) 8 57 (s, 1H), 8.50 (d, ./= 3.0 Hz, 1H), 7.95 (dd, J= 8.7, 3.0 Hz, 1H), 7 67 (d, ,/ = 8.7 Hz, 1 1 1). 7 57 (s, 1 1 1). 7.40 (s, 1 1 1). 3.98 (s, 3H), 3.97 (s, 3H) ppm; MS m/e 318.1 (M i l) |
83% | Potassium t-butoxide (1 mL, 1 mmol, 1 M in THF) was added to 2-chloro-5-hydroxypyridine (198 mg, 1.5 mmol) under inert atmosphere. The reaction mixture was stirred at room temperature for 15 min, then a solution of 6,7-dimethoxy-4-chloroquinozoline (225 mg, 1 mmol) in DMSO (1 mL) was added. The resulting solution was heated to 75 C for 2 h. The reaction mixture was quenched with H20 (50 mL) and EtOAc (2 x 50 mL) was added to extract the aqueous solution. The combined organic layers were dried over Na2S04 then concentrated under vacuum. The residue was purified by flash chromatography (eluting with 60-(at)70% EtOAc in hexanes) to give 4-[(6-chloropyridin-3-yl)oxy]-6,7-dimethoxyquinazoline (264 mg; 0.83 mmol; 83% yield) ; MS (APCI) (M+H)+ 318. ¹H NMR (400 MHz, CHLOROFORM-D) 6 ppm 4.04 (s, 3 H) 4.05 (s, 3 H) 7.42 (d, (at)8.6 Az, 1 H) 7.48 (s, 1 H) 7.63 (dd, J=8.6, 3.0 Hz, 1 H) 8.38 (d, JL2.8 Hz, 1 H) 8.57 (s, 1 H). | |
9.1g | With dmap; In dimethyl sulfoxide; at 20 - 80℃; for 2h;Inert atmosphere; | Under the argon, the DMAP (4.4g) added to the 4-chloro -6,7-dimethoxyquinazoline (8.0g) and 6-chloro-pyridine-3-ol (4.6g) of suspension in DMSO (20 ml), the bath temperature (80 C) heating and stirring 2 hours, at room temperature and to a cup. Later, the reaction solution is diluted with ethyl acetate, and washing water and saturated sodium bicarbonate aqueous solution. The organic layer is dried with anhydrous sodium sulfate and concentrated. The resulting residue with hexane-ethyl acetate (3:1) washing, to obtain the title compound (9.1g), which has the following physical property value. |
9.1 g | With dmap; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere; | Example 7 4-[(6-chloro-3-pyridinyl)oxy]-6,7-dimethoxy quinazoline Under an argon atmosphere, DMAP (4.4 g) was added to a DMSO suspension (20 mL) of 4-chloro-6,7 dimethoxy quinazoline (CAS registration No: 13790-39-1) (8.0 g) and 6-chloropyridine-3-ol (4.6 g), and the mixture was heated and stirred at a bath temperature (80C) for two hours. The mixture was allowed to cool to room temperature. The reaction solution was diluted with ethyl acetate, and washed with water and a saturated sodium hydrogen carbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate and concentrated, and the resulting residue was washed with hexane-ethyl acetate (3:1) to obtain the title compound (9.1 g) having the following physical property values. TLC: Rf 0.16 (hexane: ethyl acetate =1:1); 1H-NMR (DMSO-d6): δ 3.97, 3.99, 7.41, 7.58, 7.69, 7.97, 8.50, 8.57. |