Structure of 1073182-59-8
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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. : | 1073182-59-8 |
Formula : | C7H7ClN2O2 |
M.W : | 186.60 |
SMILES Code : | O=C(OC)C1=C(N)C=NC(Cl)=C1 |
MDL No. : | MFCD11848213 |
InChI Key : | CERGHRQGKYIIED-UHFFFAOYSA-N |
Pubchem ID : | 53418344 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.21 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.16 mg/ml ; 0.00624 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.52 |
Solubility | 0.565 mg/ml ; 0.00303 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.36 |
Solubility | 0.815 mg/ml ; 0.00437 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 |
-6.34 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) |
1.85 |
* 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 |
---|---|---|
67.7% | In methanol; hexane; ethyl acetate; at 24 - 30℃; for 0.5h;Inert atmosphere; | To a solution of compound 6a (4.0 g, 23.2 mmol) in EtOAc/MeOH=1: 1 (60 mL) was added TMSCH 2N 2 (23.2 mL, 46.4 mmol, 2 M in hexane). The resulting mixture was stirred at 24-30C for 30 min. The reaction mixture was poured into H2O (30 mL), and extracted with EtOAc (50 mL 3). The combined organic layers were washed with water (20 mL 3) and brine (20 mL), dried over Na 2SO 4 and concentrated in vacuo to give the title compound 6b (3.1 g, 67.7% yield) as a yellow solid. LCMS: Rt = 0.672 min in 5-95AB_220&254. lcm chromatography (ACSSH-LCMS-AB MERCK RP18 2.5-2mm), MS (ESI) m/z=186.9 [M+H] +. 1H NMR (400MHz, DMSO-d 6) delta 8.06 (s, 1H), 7.50 (s, 1H), 6.79 (br s, 2H), 3.84 (s, 3H). |
In methanol; diethyl ether; toluene; at 20℃; for 2h; | Step 4 : Preparation of S-amino-S-chloroisonicotinic acid methyl ester; 5-Amino-2-chloroisonicotinic acid (1.72 g) was suspended in methanol (20 mL) and toluene (60 mL) was added. A solution of (trimethylsilyl ) diazomethane (2.0 M in diethyl ether, 6.5 mL) was added slowly to the suspension. Within 5 to 10 minutes after addition, the suspension turned into a solution. After 2 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 3x with ethyl acetate. The combined organic layer was washed with saturated bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuum.The residue was purified by column chromatography (silica gel 60, chloroform/ethyl acetate = 20:1, Rf = 0.30 in chloroform/ethyl acetate = 3:1) to afford 1.50 g of the <n="408"/>title compound of the formulaas a white solid.1H-NMR (DMSO-D6) delta (ppm) : 3.83 (3H, s) , 6.77 (2H, s), 7.48 (IH, s) , 8.05 (IH, s) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.1 g | With sulfuric acid;Reflux; Inert atmosphere; | [00480] To a stirred solution of <strong>[171178-46-4]5-tert-butoxycarbonylamino-2-chloro-isonicotinic acid</strong> (crude, 8.0 g) in methanol (50 mL) was added H2SO4 (5.0 mL). The mixture was then heated to reflux overnight. The reaction was cooled to room temperature and was concentrated in vacuum. The residue was diluted with water. The aqueous mixture was neutralized with sat. NaHCC>3 to pH = 8 and extracted with EA (100 mL x2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2S04 and filtered. The filtrate was evaporated in vacuum to residue, which was purified by silica gel |
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