Structure of 247109-15-5
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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. : | 247109-15-5 |
| Formula : | C9H9N3OS |
| M.W : | 207.25 |
| SMILES Code : | NC1=NN=C(C2=CC=CC(OC)=C2)S1 |
| English Name : | 5-(3-Methoxyphenyl)-1,3,4-thiadiazol-2-amine |
| MDL No. : | MFCD00628650 |
| InChI Key : | ANOZGAXEWJZHBU-UHFFFAOYSA-N |
| Pubchem ID : | 819785 |
| Num. heavy atoms | 14 |
| Num. arom. heavy atoms | 11 |
| Fraction Csp3 | 0.11 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 56.24 |
| TPSA ? Topological Polar Surface Area: Calculated from |
89.27 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 |
1.65 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.8 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.94 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.41 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.73 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.61 |
| Solubility | 0.504 mg/ml ; 0.00243 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-3.14 |
| Solubility | 0.151 mg/ml ; 0.000728 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.21 |
| Solubility | 0.127 mg/ml ; 0.000611 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 |
No |
| 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) |
Yes |
| 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 |
-6.39 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) |
2.49 |
* 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 iron(III) chloride In ethanol for 2h; Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogenchloride; copper; acetic acid; sodium nitrite at 15 - 20℃; for 4h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: conc. HCl, aq. NaNO2, copper, glacial acetic acid / 4 h / 15 - 20 °C 2: 60 percent / 1.) hydrazine hydrate, 2.) HCl / ethanol / 4 h / Heating |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 84% | Stage #1: thiosemicarbazide; 3-Methoxybenzoic acid With trichlorophosphate at 75℃; for 1h; Stage #2: With water at 20℃; for 4h; Reflux; | |
| 56.6% | With trichlorophosphate at 20 - 75℃; for 4.5h; | 4.2.1. Synthesis of 2-amino-5-aryl-1, 3, 4-thiadiazole derivatives General procedure: The substituted benzoic acid (0.02 mol) and the thiosemicar-bazide (0.02 mol) were mixed and placed in a 100 mL three-necked flask, and then POCl 3 (7 mL) was added dropwise to the3cold mixture with stirring. It was first heated to reflux (75°C,0.5 h) and then cooled to room temperature. 25 mL of water wasadded under cold water bath conditions. Finally, heating to reflu(4 h). TLC (Thin Layer Chromatography) monitored the progress ofthe reaction. After the reaction was completed, stop heating andallow it to cool naturally. 40% NaOH was slowly added to adjustthe pH to 8, filtered to obtain the solid powder, recrystallized fromethanol, and dried to obtain the product. |
| With trichlorophosphate at 0℃; for 4.5h; Reflux; |
| With trichlorophosphate | ||
| Stage #1: 3-Methoxybenzoic acid With trichlorophosphate at 20℃; for 0.333333h; Stage #2: thiosemicarbazide for 1h; Reflux; | 4.1.2.1. Procedure for the synthesis of 2a-o General procedure: A mixture ofcorresponding acid, 1 (2.00 mmol), and POCl3 (0.80 ml) wasstirred for 20 min at room temperature. Then, thiosemicarbazide(2.0 mmol, 0.182 g) was added, and theresulting suspension was refluxed for 1 h. After cooling theflask in an ice bath, 2.4 ml of distilled water was addedcarefully, and refluxwas continued for 1 h. The mixturewasthen cooled to the room temperature, saturated aqueoussolution of NaOH was added until pH 8.5 was reached, andthe suspensionwas stirred for 1 h at the room temperature.The formed precipitate of the corresponding 2-amino-1,3,4-thiadiazole derivative (2aeo) was then filtrated, driedover CaCl2, and recrystallized from hot 50% aqueous EtOH. | |
| With trichlorophosphate at 80℃; for 2.5h; | 3.2.1. Preparation of compounds A1-A24 General procedure: A mixture of different forms of substituted benzoic acid (1.0 mmol), thiosemicarbazide (91.1 mg, 1.0 mmol), and POCl3 (0.6 mL) was warmed (150 min at 80 C), cooled toroom temperature, and then 2mL of water was then added to this solution. Solutionwas then refluxed for 240 min, cooled, and adjusted to a pH of 8 via adding NaOH(40%) in a dropwise manner with constant stiring. Resultant precipitate/residue wasthen filtered/passed through column chromatography for generating purified A1-A24with yields from 74-88%. | |
| With trichlorophosphate at 80℃; for 2.5h; | 3.2.1. Preparation of compounds A1-A24 General procedure: A mixture of different forms of substituted benzoic acid (1.0 mmol), thiosemicarbazide (91.1 mg, 1.0 mmol), and POCl3 (0.6 mL) was warmed (150 min at 80 C), cooled toroom temperature, and then 2mL of water was then added to this solution. Solutionwas then refluxed for 240 min, cooled, and adjusted to a pH of 8 via adding NaOH(40%) in a dropwise manner with constant stiring. Resultant precipitate/residue wasthen filtered/passed through column chromatography for generating purified A1-A24with yields from 74-88%. | |
| With trichlorophosphate at 60℃; for 1h; | General procedure: Acid 1 (1 mmol) and thiosemicarbazide (1.2 mmol) were added to POCl3 (1 ml), and the above mixture was stirred at 60 C for 1 h. Subsequently, the reaction solution was added into water drop by drop and Sodium hydroxide (2 M) was added to adjust the pH to 8.0, the crude product 2 was filtered off. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 24h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 54% | With triethylamine In 1,4-dioxane at 100℃; for 0.166667h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In benzene for 0.75h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 7% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; | 146 Example 146 N-[5-(3-methoxyphenyl)-l,3,4-thiadiazol-2-yl]-3-[(4-methylpiperazin-l-yl)acetyl]amino}-4- (trifluoromethoxy)benzamide To a solution of the compound of intermediate 126 (150 mg, 0.32 mmol) and 5-(3-methoxyphenyl)- l,3,4-thiadiazol-2-amine (132 mg, 0.64 mmol, 2 equiv) in DMF (2.0 mL) was added (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 334 mg, 0.64 mmol, 2 equiv) and diisopropylethylamine (0.28 mL, 1.60 mmol, 5 equiv). The resulting mixture was stirred at room temperature over night and was then poured into a mixture of water and ethanol (9/1). The precipitate was collected by filtration, washed with water and dried. Purification by HPLC (Waters Autopurificationsystem, column: XBrigde C18 5μιτι 100x30 mm, solvent: water / methanol + 0.2% ammonia (32%) gradient, rate: 70 mL/min, temperature: room temperature) yielded 13.0 mg (7% of theory) of the title compound. 1H-NM (300 MHz, DMSO-d6): δ [ppm] = 2.27 (s, 3H), 2.57 - 2.70 (m, 5H), 3.24 (s, 2H), 3.86 (s, 3H), 7.05 - 7.13 (m, 1H), 7.40 - 7.55 (m, 3H), 7.62 (d, 1H), 8.01 (dd, 1H), 8.97 (d, 1H), 9.92 (s, 1H), 12.86 (s, 1H). LC-MS (Method 3): Rt = 0.76 min; MS (ESIpos): m/z = 551 [M+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78.5% | With formic acid; phosphorus pentoxide |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: ethanol / 18 h / Inert atmosphere; Reflux 2: tin(II) chloride dihdyrate / ethanol / 1.5 h / Inert atmosphere; Reflux |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: ethanol / 18 h / Inert atmosphere; Reflux 2: tin(II) chloride dihdyrate / ethanol / 1.5 h / Inert atmosphere; Reflux 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere; Cooling with ice |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 57% | In ethanol for 18h; Inert atmosphere; Reflux; | 10 5.1.3. General procedure B for the synthesis of compounds 3b-i, 3koand 4a-c General procedure: A mixture of the appropriate 2-amino-5-substituted 1,3,4-thiadiazole 1b-o or 4-arylthiazol-2-amine 2a-c (2 mmol) and 2-bromo-1-(3-nitrophenyl)ethanone (488 mg, 2 mmol) in anhydrousEtOH (20 mL) was stirred at reflux for 18 h. The solution wascooled to room temperature, the solvent was removed in vacuo, andsaturated aqueous NaHCO3 solution was added to make themixture basic (pH 8e9). The mixture was extracted with CH2Cl2(3 15 mL), the combined organic phases were washed with brine(10 mL) and dried with anhydrous Na2SO4. After removal of thesolvent, the residue was stirred with ethyl ether (10 mL) andfiltered to afford the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80.3% | Stage #1: 2-((pyridin-4-ylmethyl)amino)nicotinic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: 5-(3-methoxyphenyl)-1,3,4-thiadiazol-2-amine In N,N-dimethyl-formamide at 20℃; for 16h; Cooling with ice; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: sodium acetate / water; ethanol / 0.25 h / 20 °C 2: acetic acid; iodosylbenzene; dihydrogen peroxide / dimethyl sulfoxide / 4 h / 60 °C / Green chemistry |

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