Structure of 1211533-83-3
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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. : | 1211533-83-3 |
Formula : | C6H7BrN2O |
M.W : | 203.04 |
SMILES Code : | COC1=C(Br)C=CC(N)=N1 |
MDL No. : | MFCD08062947 |
InChI Key : | STTFWVSVDMLUCF-UHFFFAOYSA-N |
Pubchem ID : | 53420205 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
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 | 42.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.31 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.42 |
Solubility | 0.769 mg/ml ; 0.00379 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.12 |
Solubility | 1.54 mg/ml ; 0.00761 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.65 |
Solubility | 0.453 mg/ml ; 0.00223 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 |
-6.47 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 |
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) |
1.95 |
* 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 |
---|---|---|
37% | With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; for 1h;Inert atmosphere; | Example 43a5-(6-Amino-2-methoxypyridin-3-yl)-1-methylpyridin-2(1H)-one1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (CAS 1002309-52-5, 1.088 g, 4.63 mmol), 5-bromo-6-methoxypyridin-2-amine (CAS 1211533-83-30, 94 g, 4.63 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)chloride dichloromethane complex (0.113 g, 0.14 mmol) and potassium carbonate (aqueous 2M) (6 mL, 12.00 mmol) in dioxane (10 mL) were heated under argon to 80° C. for 1 h.The mixture was allowed to cool and was filtered through a short pad of Celite.The pad was washed with EtOAc (100 mL).The filtrate was collected and the solvent was removed by rotary evaporation.The crude product was added to a silica gel column and was eluted with 0-3percent MeOH in DCM.The collected fractions were combined and the solvent was removed by rotary evaporation.The residue was redissolved in DCM and the mixture was washed with saturated aqueous Na2CO3, dried over K2CO3, filtered and the solvent was removed by rotary evaporation to yield the title compound (0.402 g, 37percent).1H NMR (500 MHz, DMSO-d6) delta ppm 3.44 (s, 3H) 3.78 (s, 3H) 5.98 (s, 2H) 6.07 (d, 1H) 6.37 (d, 1H) 7.33 (d, 1H) 7.56 (dd, 1H) 7.72 (d, 1H). MS (ES+) m/z 232.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 20℃; for 0.03h; | General procedure: To a solution of 5-bromo-6-methoxypyridin-2-amine (475 mg, 2.34 mmol) in dioxane (6 mL) was added tert-butyl 4-(tetramethyl-l,3,2-dioxaborolan-2-yl)- 1,2,3,6-tetrahydropyridine-l-carboxylate (1425 mg, 4.61 mmol), Pd(OAc)2 (55 mg, 0.24 mmol), 5- Phos (203 mg, 0.49 mmol) and K3PO4 solution (1570 mg in 2 mL water, 7.40 mmol) at room temperature. The resulting mixture was stirred for 3 h at 120 C. When the reaction was done, the reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in hexane (0 % to 60 % gradient) to yield tert-butyl 4-(6- amino-2-methoxypyridin-3-yl)-l,2,3,6-tetrahydropyridine-l-carboxylate as an yellow oil (437 mg, 61 %). MS: m/z = 306.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃;Inert atmosphere; | A 5 mL microwave vial containing a Teflon stirred bar was charged with 5-bromo-6- methoxypyridin-2-amine (90 mg, 0.44 mmol, leq.), 2,3-dichloro phenylboronic acid (97.2 mg, 0.51 mmol, 1.15 eq.), Na2C03 (140 mg, 1.32 mmol, 3 eq.) followed by the addition of a mixture of Toluene/EtOH/hhO: 3.2/0.5/0.5 (O. lmmol/mL). The vessel was evacuated and backfilled with nitrogen (this process was repeated a total of 3 times) and Pd(PPh )4 (25.6 mg, 0.022 mmol, 0.05 eq.) was introduced. The reaction mixture was then capped properly and placed in a preheated oil bath at l20C until complete conversion of the starting material (usually 3h). The reaction mixture was then concentrated under vacuum and the crude product was purified by chromatography on silica gel using EtOAc/heptane: 1/1 to afford the expected product 7a as a solid (70 mg, 59%)XH-NMR (400 MHz, CDCI3): d 7.39 (dd, J= 6.9 Hz, 2.8 Hz, 1H), 7.25 (d, J= 7.8 Hz, 1H), 7.18 (m, 2H), 6.13 (d, J= 7.8 Hz, 1H), 4.28 (bs, 2H), 3.83 (s, 3H).13C-NMR (101 MHz, CDCI3) d : 159.9, 157.0, 141.4, 138.8, 133.2, 132.8, 130.2, 129.2, 126.8, 111.2, 99.4, 53.6. |
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