Structure of 28783-38-2
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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. : | 28783-38-2 |
Formula : | C7H10ClNS |
M.W : | 175.68 |
SMILES Code : | C12=C(C=CS2)CCNC1.[H]Cl |
MDL No. : | MFCD08448167 |
InChI Key : | VQEOIFRMJGFLQH-UHFFFAOYSA-N |
Pubchem ID : | 25067333 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.66 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.611 mg/ml ; 0.00348 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 0.868 mg/ml ; 0.00494 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.531 mg/ml ; 0.00302 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) |
Yes |
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 |
-6.07 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 |
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) |
2.06 |
* 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 |
---|---|---|
With triethylamine; In dichloromethane; | g) Synthesis of 1-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-6-phenylhexan-1-one To a solution of 0.272 g (1.548 mmol) of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong>, 0.33 g (1.7 mmol) of 6-phenylhexanoic acid and 0.86 ml (6.2 mmol) of triethylamine in 30 ml of dichloromethane, 0.28 ml (1.9 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into aqueous sodium hydroxide and extracted with dichloromethane 3 times. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 3/1) to yield the desired product. Colorless oil Yield 0.503 g (100%) 1 H-NMR (CDCl3, 200 MHz) delta1.340-1.478 (2H, m), 1.577-1.789 (4H, m), 2.340-2.450 (2H, m), 2.573-2.786 (4H, m), 3.690 (1.2H, t, J=5.7 Hz), 3.868 (0.8H, t, J=5.8 Hz), 4.654 (0.8H, s), 4.800 (1.2H, s), 6.775-6.821 (1H, m), 7.134-7.314 (6H, m); IR (neat) 2929, 1645, 1427, 1227, 702 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In methanol; | f) Synthesis of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride To a solution of 1.427 g (5.962 mmol) of 6-tert-butoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine in 5 ml of methanol, 3 ml of concentrated hydrochloric acid was added, followed by stirring at room temperature for 1 hour. The solvent was distilled off under reduced pressure to yield the desired product. White crystal Yield 1.025 g (98%) 1 H-NMR (CD3 OD, 200 MHz) delta3.022 (2H, tt, J=1.6&6.2 Hz), 3.507 (2H, t, J=6.3 Hz), 4.430 (2H, s), 6.915 (1H, d, J=5.0 Hz), 7.386 (1H, d, J=5.2 Hz); IR (nujol) 2777-2416, 1157, 1090, 1036, 702 cm-1; Anal. Calcd for C7 H10 ClNS: C, 47.86; H, 5.74; N, 7.97. Found: C, 47.82; H, 5.63; N, 8.02. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triethylamine;dmap; In ethyl acetate; N,N-dimethyl-formamide; | (a) To the solution of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (5.2 g) in DMF (60 ml) were added di-t-butyl dicarbonate (7.11 g), triethylamine (6.58 g) and a catalytic amount of 4-dimethylaminopyridine, and the mixture was stirred at room temperature for 1 hour. After the addition of ethyl acetate (300 ml) and washed with saturated saline, the mixture was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel to give 4.67 g of 5-t-butoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine from the fraction eluted with n-hexane:ethyl acetate=2:1 (yield, 88%). 1 H-NMR (CDCl3) delta:1.48 (s, 9H), 2.70 (brs, 2H), 3.68 (brs, 2H), 4.62 (brs, 2H), 6.79 (d, J=5 Hz, 1H), 7.13 (d, J=5 Hz, 1H). FDMS (m/z): 239 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bromine; In acetic acid; at 20℃; for 1.5h; | A solution of bromine (139 mg, 0.87 mmol) in acetic acid (0.5 mL) was added to a solution of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (150 mg, 0.85 mmol) in acetic acid (3 mL) and the mixture left to stir at ambient temperature for 1.5 h. The resultant precipitate was collected by filtration, washed with diethyl ether and left to air dry to afford the title compound as an off-white solid (230 mg, 90%). 1H NMR (DMSO-D6, 300MHz): 9.19 (s, 2H), 7.09 (s, 1H), 4.29-4.26 (m, 2H), 2.86-2.78 (m, 2H), 2.52-2.48 (m, 2H). LCMS (Method B): RT= 1.65 min, M+H+ = 218/220. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; | 5.109 3-{4-[4-(4,7-DIHYDRO-5H-THIENO[2,3-C]PYRIDIN-6-YLMETHYL)-BENZYLOXY]-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL}-PIPERIDINE-2,6-DIONE To the CH3CN (10 ml) solution of 3-(4-(4-(bromomethyl)benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.359 g, 0.810 mmol) was added <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (0.171 g, 0.972 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.402 ml, 2.430 mmol). It became a clear solution after DIPEA was added. The mixture was stirred at room temperature overnight. Solvent was evaporated and to the residue was added methylene chloride (80 ml). The mixture was washed with water (2*60 ml), brine (50 ml), dried and concentrated to an off-white solid, which was purified by silica gel column (MeOH/CH2Cl2) to give 3-{4-[4-(4,7-Dihydro-5H-thieno[2,3-c]pyridin-6-ylmethyl)-benzyloxy]-1-oxo-1,3-dihydro-isoindol-2-yl}-piperidine-2,6-dione as a white solid (0.304 g, 74% yield). HPLC: Waters Symmetry C-18, 3.9*150 mm, 5 mum, 1 mL/min, 240 nm, gradient from 10/90 to 90/10 in 5 min, isocratic at 90/10 for 5 min (CH3CN/0.1% H3PO4), 4.61 min (98.1%). 1H NMR (DMSO-d6) delta 1.89-2.08 (m, 1H, CHH), 2.35-2.48 (m, 1H, CHH), 2.53-2.68 (m, 3H, CHH, CH2), 2.68-2.77 (m, 2H, CH2), 2.82-3.00 (m, 1H, CHH), 3.59 (s, 2H, CH2), 3.68 (s, 2H, CH2), 4.20-4.48 (m, 2H, CH2), 5.11 (dd, J=5.2, 13.3 Hz, 1H, NCH), 5.24 (s, 2H, CH2), 6.82 (d, J=5.1 Hz, 1H, Ar), 7.28 (d, J=5.1 Hz, 1H, Ar), 7.31-7.42 (m, 4H, Ar), 7.43-7.56 (m, 3H, Ar), 10.97 (s, 1H, NH). 13C NMR (DMSO-d6) delta 22.36, 25.12, 31.20, 45.10, 49.59, 51.36, 51.59, 60.50, 69.45, 115.00, 115.24, 122.61, 126.99, 127.72, 128.83, 129.81, 129.95, 132.46, 133.32, 133.47, 135.35, 138.29, 153.53, 168.01, 170.96, 172.82. LC/MS m/e=502. Anal Calcd for C28H27N3O4S (+0.5 H2O): C, 65.86; H, 5.53; N, 8.23. Found: C, 65.64; H, 5.44; N, 8.04. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In dichloromethane; at 20℃; for 4.5h; | 4,5,6,7-tetrahydrothiophene[2,3-c]pyridine hydrochloride (15.0g, 85.38mmol) and triethylamine (24.0mL, 170.77mmol) was dissolved in In dichloromethane (150mL), was added di-tert-butyl dicarbonate (22.36g, 102.46mmol). It was stirred at roomtemperature for 4.5 hours. After completion of the reaction, Was added water (50mL), (30mL × 2) and extracted withdichloromethane. The combined organic phases were washed with water (20mL × 2), saturated brine (30 mL) , Dried over anhydrous sodium sulfate. Filtered and the solvent evaporated under reduced pressure and the crude product purified bycolumn chromatography (petroleum ether/ethyl acetate (v/v=20/1), obtained as a white solid (20.49g, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | (R)-2-(9-(Pyridin-2-yl)-6-oxa[4.5]decane-9-yl)acetaldehyde (21B) (0.259 g, 1.0 mmol) was dissolved in dichloromethane. 36mL)In the middle, sodium sulfate (1.42g, 5.0mmol)and4,5,6,7-4,5,6,7 tetrahydroisothiophene [3, 2-c]pyridine hydrochloride(0.22 g, 1.25 mmol) was added to the reaction, which was reacted overnight at room temperature.Sodium borohydride (0.048 g, 1.25 mmol) was added to the reaction.The reaction was stirred for 30 minutes, then methanol (10 mL) was added and the mixture was stirred for 1 hour.The reaction was quenched with water (30 mL) andEtOAc.The combined organics were washed with saturated sodium chloride (30 mL)Dry over anhydrous sodium sulfate, filter, and concentrate the filtrate.Column chromatography on crude material (dichloromethane/methanol (v/v) = 40:1 to 20:1)Yellow oily liquid(R)-5-(2-(9-(pyridin-2-yl)-6-oxaspiro[4.5]decane-9-yl)ethyl)-4,5,6,7 tetrahydroisothiophene [3,2-c]pyridine (22A)(0.050 g, yield 10%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; at 25 - 40℃; for 24.0h; | Add in 2L reaction bottle at 25~35C4,5,6,7-tetrahydrothienopyridine hydrochloride 170.0 g, 30% potassium carbonate 897.5 g,And a solution of methyl 2-benzenesulfonate-2-(2-chlorophenyl)acetate in 340.0 g,After the completion of the dropwise addition, the mixture was stirred at 40 C for 24 hours. Down to room temperature,The organic phase was washed with water and dried over anhydrous sodium sulfate. Evaporating the solvent to obtain an oily liquid,215.3 g of dichloromethane was recovered to obtain 338 g of clopidogrel free base.The yield was 95.9% and the purity was 93.42%. |
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