Structure of 39891-13-9
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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. : | 39891-13-9 |
Formula : | C7H6ClNO2 |
M.W : | 171.58 |
SMILES Code : | O=C(O)CC1=CC=C(Cl)N=C1 |
MDL No. : | MFCD01863172 |
InChI Key : | XWVPSJPQWOVRHJ-UHFFFAOYSA-N |
Pubchem ID : | 14071571 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
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 | 40.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.66 |
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 |
1.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.98 |
Solubility | 1.79 mg/ml ; 0.0104 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.93 |
Solubility | 2.0 mg/ml ; 0.0117 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.41 |
Solubility | 0.661 mg/ml ; 0.00385 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 |
-6.44 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 |
0.56 |
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) |
1.61 |
* 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 |
---|---|---|
Intermediate 32; 2-(6-Chloropyridin-3-yl)-acetamide; To 10.0 g (58.3 mmol) (2-chloropyridyl)-5-acetic acid in 150 mL THF are added 9.45 g (58.3 mmol) CDI and the mixture is stirred at 45 C. for 1 h. Then 28.0 g (291 mmol) NH4CO3 are added and the mixture is stirred at r.t. over night. The reaction mixture is poured onto water and extracted with EtOAc. The organic layer is dried with MgSO4 and the solvent is removed in vacuo. The residue is triturated with TBME and recrystallized from EtOH.C7H7ClN2O (M=170.6 g/mol)ESI-MS: 171 M+H]+ Rf (TLC): 0.45 (silica gel, DCM/MeOH 9/1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sulfuric acid; for 4h;Reflux; | To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 ml_). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over MgS04 and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95 %). |
95% | With sulfuric acid; for 4h;Reflux; | To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 ml_). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over magnesium sulphate and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95 %). |
95% | With sulfuric acid; for 4h;Reflux; | Step 1: To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 mL). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over MgSO4 and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95%). |
95% | With sulfuric acid; for 4h;Reflux; | Step 1:[0815]To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 mL). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over magnesium sulfate and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95%). |
87.2% | With sulfuric acid; at 90℃; | 2-(6-chloropyridin-3-yl)acetic acid (4g, 22.4 mmol), ethanol (20 mL) and concentrated sulfuric acid (0.4 mL) were added to a 100 mL single-mouth bottle, and heated to 90 C to react overnight. After reaction, the mixture was cooled to room temperature, neutralized with saturated sodium bicarbonate, and extracted with ethyl acetate. The organic layers were combined, the solvent was dried with rotation under vacuum under an increased pressure, and the obtained product separated by a silica gel column (petroleum ether: ethyl acetate = 5:1) to give the product (colorless oil, 3.75 g), with a yield of 87.2%. 1H NMR (400 MHz, CDCl3) delta 8.28 (d, J= 1.5 Hz, 1H), 7.61 (dd, J= 8.2, 2.1 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.59 (s, 2H), 1.25 (t, J = 7.1 Hz, 3H). |
79% | Example 28. Synthesis of K002. To a suspension of 6-cholro-2-pyridineacetic acid methyl ester (10 g, 58.2 mmol) was added cone, sulfuric acid (30 mL) and the reaction was heated to 70 C for 4 hr. The reaction mixture was cooled to room temperature and concentrated and the resulting residue was suspended in H20 (1L) and pH was adjusted to pH = 9 with sodium carbonate. The solution was extracted with ethyl acetate. The organics were washed with brine, dried over Na2S04, filtered and concentrated to give the crude product that was purified by flash column chromatography (30% EtOAC: 70% heptanes) to give the desired product 8.58 g, 79%.LC-MS: (ES, m/z): 186 [M+H]+ 1H-NMR: (400MHz, MeCN- J, ppm): delta 3.66 (m, 5H), 7.36(d, 1H), 7.67(d, 1H), 8.26(s, 1H). | |
68.78% | With sulfuric acid; for 4h;Reflux; | Synthesis of compound 74.2. To a solution of compound 74.1 (lOg, 0.0584mol, l .Oeq.) in ethanol (100 mL) was added drop wise H2SO4 (2mL). Reaction was stirred for 4 hours at reflux temperature. After completion of the reaction, solvent was evaporated and water was added. Mixture was extracted using ethyl acetate (150ml x2). Organic layer was washed with saturated sodium bicarbonate solution (70ml x 2), dried over sodium sulfate and concentrated under reduced pressure at 45C to afford compound 74.2 (8g, 68.78%). MS (ES): m/z 200.4 [M+H] + |
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