Structure of 4651-82-5
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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. : | 4651-82-5 |
Formula : | C5H4N2S |
M.W : | 124.16 |
SMILES Code : | NC1=C(C=CS1)C#N |
MDL No. : | MFCD00706298 |
InChI Key : | XVGHZFWFGXDIOU-UHFFFAOYSA-N |
Pubchem ID : | 736607 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352+P312+P362+P364-P304+P340+P312-P305+P351+P338+P337+P313-P501 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 33.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.29 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.52 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.29 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.03 |
Solubility | 1.16 mg/ml ; 0.00933 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.77 |
Solubility | 0.212 mg/ml ; 0.00171 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.35 |
Solubility | 5.56 mg/ml ; 0.0448 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) |
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 |
-5.98 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) |
2.19 |
* 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 |
---|---|---|
64% | With lithium diisopropyl amide; In tetrahydrofuran; hexane; at 40℃; for 2.25h;Inert atmosphere; | Al : 4-amino-5 -(6-(4-methylpiperazin- 1 -yl)- 1 H-benzo [dl imidazol-2-yl)thieno [2.3-bl pyridin- 6(7H)-one To a solution of ethyl 2-(6-(4-methylpiperazin-l-yl)-lH benzo[d]imidazol-2-yl)acetate (2.42 g, 8.05 mmol) and 2 aminothiophene-3-carbonitrile (1.0 g, 8.05 mmol) in anh THF (40 mL) at 40 C added LDA (40 mL, 1 M in THF/hexane, 40 mmol) dropwise over 15 min under Ar. The resulting brown solution was stirred at 40 C for 2 h and then quenched with aq NH4CI (50 mL) at rt. The mixture was diluted with H20 (125 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed once with H20, dried over Na2S04, and concentrated to give crude product. The crude product was triturated with DCM (20 mL) followed by MeOH (25 mL) to give the title compound as a light brown solid (1.95 g, 64%). The free base (1.95 g) was suspended in MeOH (50 mL) and added 1 M HCl-Et20 (13 mL) at rt. The suspension was stirred for 15 min at rt and concentrated under vacuum and azeotroped with MeOH (2 x 25 mL) to give the HC1 salt as a dark brown solid (2.28 g, 62%); NMR (400 MHz, CD3OD) δ 7.69 (d, J=9.2 Hz, 1H), 7.52 (d, J=5.6 Hz, 1H), 7.36 (dd, J=8.8, 2.4 Hz, 1H), 7.30 (d, J=2.4 Hz, 1H), 7.19 (d, J=5.6 Hz, 1H), 3.97-3.93 (m, 2H), 3.70- 3.67 (m, 2H), 3.39-3.35 (m, 2H), 3.34-3.18 (m, 2H), 3.01 (s, 3H); MS ESI [M + H]+ 381.2, calcd for [C19H20 N6OS+ H]+ 381.1. |
27.6% | With lithium diisopropyl amide; In tetrahydrofuran; at 40℃; for 2.66667h;Inert atmosphere; | Ethyl 2-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)acetate (866 mg, 2.864 mmol, 1.0 eq)And 2-aminothiophene-3-carbonitrile (355.6 mg, 2.864 mmol, 1.0 eq) was dissolved in THF.Warm up to 40 C under nitrogen protection,Lithium diisopropylamide (2 mol/L, 7.134 mL, 14.32 mmol, 5.0 eq) was slowly added dropwise.After about 40 min addition, the reaction was continued for 2 h, and the reaction was monitored by LC-MS.The reaction solution was added to a saturated aqueous solution of ammonium chloride (50 mL).Extracted with EA (50 mL×3), the organic phases were combined, washed with water (30mL)Concentrated, and the crude product was washed with DCM (1 mL).The product was obtained by suction filtration (301 mg, yield 27.6%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate; In toluene; at 80℃; | To a solution of a mixture of 2-aminothiophene-3-carbonitrile (1.39 g, 11.2 mmol) and <strong>[422-64-0]pentafluoropropionic acid</strong> (1.20 mL, 11.42 mmol) in toluene (10 mL) was added phosphorusoxychloride (3.5 mL, 37.6 mmol) and the reaction mixture was heated at 80 °C overnight. LC-MS analysis of the reaction mixture after overnight heating showed an 1:1 mixture of the desired product and the intermediate product: 2-(perfluoroethyl)thieno[2,3-djpyrimidin-4(3H)-one. A second batch of neat POd3 (5.0 mL) was added to the above residue and the reaction mixture was heated under refluxing conditions for 1 h to give a dark orange-brown suspension. The solvent was evaporated in vacuo toafford a dark orange-brown gummy solid. The gummy residue was poured onto crushed ice-water and the mixture was neutralized with a saturated NaHCO3 solution and the mixture was extracted with dichloromethane (3 x 25 mL), the aqueous and the organic layers were separated, the organic layer was dried over anhydrous Na2SO4, filtered and evaporated in vacuo and the crude product was purified by silica-gel flash chromatography to afford a very pale viscous liquid which solidified to a very paleyellow to colorless crystalline solid (794.0 mg, yield 25percent). LC-MS analysis of the solid showed the desired product with a purity >98percent and the desired product?s mass: m/z 289 (35C1M+H), and m/z 291(37dlM+H); Calcd for C3H2C1F5N2S: 288.62 1H NMR (400 MHz, CDC13): oe 7.59 (d, J = 6.00 Hz, 1H, H-5), 7.88 (d, J = 6.11 Hz, 1H, H-6); 19F NMR (376 MHz, CDC13): oe -83.68 (s, 3F, 2-CF3CF2-), -116.13 (s, 2F, CF3CF2-). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | To a solution of a mixture of 2-aminothiophene-3-carbonitrile (1.39 g, 11.2 mmol) and <strong>[422-64-0]pentafluoropropionic acid</strong> (1.20 mL, 11.42 mmol) in toluene (10 mL) was added phosphorusoxychloride (3.5 mL, 37.6 mmol) and the reaction mixture was heated at 80 °C overnight. LC-MS analysis of the reaction mixture after overnight heating showed an 1:1 mixture of the desired product and the intermediate product: 2-(perfluoroethyl)thieno[2,3-djpyrimidin-4(3H)-one. A second batch of neat POd3 (5.0 mL) was added to the above residue and the reaction mixture was heated under refluxing conditions for 1 h to give a dark orange-brown suspension. The solvent was evaporated in vacuo toafford a dark orange-brown gummy solid. The gummy residue was poured onto crushed ice-water and the mixture was neutralized with a saturated NaHCO3 solution and the mixture was extracted with dichloromethane (3 x 25 mL), the aqueous and the organic layers were separated, the organic layer was dried over anhydrous Na2SO4, filtered and evaporated in vacuo and the crude product was purified by silica-gel flash chromatography to afford a very pale viscous liquid which solidified to a very paleyellow to colorless crystalline solid (794.0 mg, yield 25percent). LC-MS analysis of the solid showed the desired product with a purity >98percent and the desired product?s mass: m/z 289 (35C1M+H), and m/z 291(37dlM+H); Calcd for C3H2C1F5N2S: 288.62 1H NMR (400 MHz, CDC13): oe 7.59 (d, J = 6.00 Hz, 1H, H-5), 7.88 (d, J = 6.11 Hz, 1H, H-6); 19F NMR (376 MHz, CDC13): oe -83.68 (s, 3F, 2-CF3CF2-), -116.13 (s, 2F, CF3CF2-). |
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