Structure of 63875-18-3
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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. : | 63875-18-3 |
Formula : | C4H5N3O2S |
M.W : | 159.17 |
SMILES Code : | O=C(C1=NSN=C1N)OC |
MDL No. : | MFCD01208070 |
InChI Key : | DOLNBTMCAGQKDX-UHFFFAOYSA-N |
Pubchem ID : | 1540439 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
106.34 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.44 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.76 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.54 |
Solubility | 4.55 mg/ml ; 0.0286 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.57 |
Solubility | 0.425 mg/ml ; 0.00267 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.63 |
Solubility | 37.6 mg/ml ; 0.236 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 |
-6.73 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 |
2.0 |
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) |
2.39 |
* 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 |
---|---|---|
2.19 g (78%) | To this crude material was slowly added 15 mL of thionyl chloride under nitrogen and the mixture was refluxed for 20 minutes. After removal of the excess thionyl chloride under reduced pressure, 100 mL of methanol was added, and the mixture was refluxed for 2 hours. The solvents were removed under reduced pressure and the solid obtained was recrystallized from methanol to afford 2.19 g (78%) of the title compound. m.p. 142-143 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,1'-carbonyldiimidazole; In tetrahydrofuran; ethyl acetate; for 2.0h;Inert atmosphere; | 4-amino-i ,2,5-thiadiazole-3-carboxylic acid (500 mg, 3.44 mmol, 1 .0 eq.) wassuspended in ethyl acetate (10 mL) and tetrahydrofuran (3 mL) with stirring under N2.Treated with solid i,i?-carbonyldiimidazole (670 mg, 4.13 mmol, 1.2 eq.).After 2 h, the reaction was quenched with methanol (18 ml). Further methanol was thenadded until all material dissolved (to a total reaction volume of 50 ml). The reactionwas evaporated to dryness to afford a crude yellow solid. The crude was partitioned between ethyl acetate and sat. NaHCO3 (aq). The organic layer was kept and the aqueous re-extracted. The combined organics were dried over Na2504, filtered and evaporated to give methyl 4-amino-i ,2,5-thiadiazole-3-carboxylate (338 mg, 61.6 %), asa yellow solid.1H NMR (400 MHz, CDCI3): oe: 5.95 (br. s, 2H), 4.00 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.6% | With pyridine; In dichloromethane; at 20.0℃; for 1.0h; | 2-(2-benzyloxy-3,6-dichloro-phenyl)acetic acid (300 mg, 0.964 mmol, 1 .0 eq.) was suspended in dichloromethane (3 ml) under N2 and a drop of N,Ndimethylformamide added. The mixture was treated with oxalyl chloride (0.17 mL, 1.93 mmol, 2.0 eq.) and immediately started to effervesce. Stirred at rt for 2.5 h.The reaction mixture was evaporated to dryness and the crude acyl chloride redissolvedin dichloromethane (2.5 ml). With stirring, solid <strong>[63875-18-3]methyl 4-amino-1,2,5-thiadiazole-3-carboxylate</strong> (153 mg, 0.96 mmol, 1.0 eq.) was added, followed by pyridine (0.16 mL,1.93 mmol, 2.0 eq.). The reaction was stirred at rt for 1 h then diluted with further dichloromethane and quenched with sat. NaHCO3 (aq). The mixture was phase- separated and the organics dried over Na2504. Evaporation to dryness gave a crudesolid which was further purified by flash column chromatography (silica, eluent 0-80 % ethyl acetate in isohexane). The target methyl 4-[[2-(2-benzyloxy-3,6-d ichlorophenyl)acetyl]amino]-1,2,5-thiadiazole-3-carboxylate was obtained as a white solid (251 mg, 57.6 %).1H NMR (400 MHz, d6-DMSO): oe: 11.46 (br. s, 1H), 7.56-7.29 (m, 7H), 4.96 (s, 2H), 4.01 (s, 2H), 3.72 (s, 3H). |
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