Structure of 1544-85-0
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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. : | 1544-85-0 |
Formula : | C7H5F2NO2 |
M.W : | 173.12 |
SMILES Code : | NC1=CC2=C(OC(F)(F)O2)C=C1 |
MDL No. : | MFCD00190144 |
InChI Key : | CVYQRDKVWVBOFP-UHFFFAOYSA-N |
Pubchem ID : | 2736893 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H317-H319-H412 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.48 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.58 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
Solubility | 0.643 mg/ml ; 0.00372 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.732 mg/ml ; 0.00423 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.33 |
Solubility | 0.802 mg/ml ; 0.00463 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) |
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 |
-6.06 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 |
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) |
2.27 |
* 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 |
---|---|---|
67% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 60℃; for 16h; | 3-[(Tert-butoxycarbonyl)amino]thiophene-2-carboxylic acid (7.3 g, 30.3 mmol) (step 2) was dissolved in DCM (155 niL), triethyl amine (12 mL), DMF (31 mL) and 2,2-difluoro- l,3-benzodioxol-5-amine (5 g, 29 mmol) was added. PyBOP (16.5 g, 32 mmol) was added and the mixture was stirred at 600C for 16 h. The reaction mixture was cooled and diluted with water and EtOAc. The organic layer was washed with water, dried with Na2SO4, and evaporated. The crude residue was purified using silica gel chromatography to yield the desired product (7.7 g, 67 %). 1H NMR (DMSO-J6) 69.95 (bs, IH), 7.95 (d, IH), 7.65, (s, IH), 7.45 (m, 2H), 7.10 (s, 2H), 1.50 (s, 9H); LCMS: 398.9 [M+H]+, RT 4.12 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.65% | To a 40 mL microwave vial were added <strong>[1171919-75-7]2-chloro-4-iodonicotinonitrile</strong> (1.451 g, 5.488 mmol), bis(2-diphenylphosphinophenyl)ether (90 mg, 0.17 mmol), palladium(II) acetate (25 mg, 0.11 mmol), cesium carbonate (2.503 g, 7.683 mmol), 2,2-difluoro-5-aminobenzodioxole (1.0 g, in 1.0 mL dioxane), and dioxane (10 mL) and was purged with N2stream for 30 min. The reaction was heated in the microwave at 150 C for 30 min. To the reaction mixture was added fert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperi dine- 1-carboxy late (Intermediate 22) ( 8.44 mL, 5.49 mmol) and was purged with N2stream for 15 min. The reaction was heated in microwave at 150 C for 30 min. To the mixture was added CDI (3.6 g, 22 mmol) and was heated at 150 C for 30 min. The reaction mixture was extracted with EtOAc and the organic phase was washed with water and brine. The precipitate was filtered off through Celite. The organic phase was over anhydrous Na2SC>4, filtered, and concentrated to dryness. The reaction mixture was purified by flash column chromatography, then by HPLC to give the title compound as a brown solid (82.4 mg, 2.65% yield). MS (ESI): mass calcd. for C25Hi9F2N705S, 567.5; m/z found, 568.0 [M+H]+.1H NMR (500 MHz, CD3OD): δ 8.16 - 8.06 (m, 2H), 7.47 (s, 1H), 7.27 - 7.20 (m, 2H), 7.15 - 7.08 (m, 1H), 7.06 (s, 1H), 6.80 (d, J= 5.9 Hz, 1H), 5.16 - 5.06 (m, 1H), 4.17 (t, J = 12.0 Hz, 1H), 4.12 - 3.97 (m, 2H), 3.13 (t, J = 12.4 Hz, 1H), 2.86 - 2.71 (m, 1H), 1.92 (t, J= 13.3 Hz, 2H), 1.83 - 1.72 (m, 1H). | |
2.65% | To a 40 mL microwave vial were added <strong>[1171919-75-7]2-chloro-4-iodonicotinonitrile</strong> (1.451 g, 5.488 mmol) , bis (2-diphenylphosphinophenyl) ether (90 mg, 0.17 mmol) , palladium (II) acetate (25 mg, 0.11 mmol) , cesium carbonate (2.503 g, 7.683 mmol) , 2, 2-difluoro-5-aminobenzodioxole (1.0 g, in 1.0 mL dioxane) , and dioxane (10 mL) and was purged with N2stream for 30 min. The reaction was heated in the microwave at 150 for 30 min. To the reaction mixture was added tert-butyl (3R) -3- [ (2-sulfanylacetyl) amino] piperidine-1-carboxylate (Intermediate 22) (8.44 mL, 5.49 mmol) and was purged with N2stream for 15 min. The reaction was heated in microwave at 150 for 30 min. To the mixture was added CDI (3.6 g, 22 mmol) and was heated at 150 for 30 min. The reaction mixture was extracted with EtOAc and the organic phase was washed with water and brine. The precipitate was filtered off through Celite. The organic phase was over anhydrous Na2SO4, filtered, and concentrated to dryness. The reaction mixture was purified by flash column chromatography, then by HPLC to give the title compound as a brown solid (82.4 mg, 2.65yield) . MS (ESI) : mass calcd. for C25H19F2N7O5S, 567.5 m/z found, 568.0 [M+H]+.1H NMR (500 MHz, CD3OD) : δ 8.16 -8.06 (m, 2H) , 7.47 (s, 1H) , 7.27 -7.20 (m, 2H) , 7.15 -7.08 (m, 1H) , 7.06 (s, 1H) , 6.80 (d, J 5.9 Hz, 1H) , 5.16 -5.06 (m, 1H) , 4.17 (t, J 12.0 Hz, 1H) , 4.12 -3.97 (m, 2H) , 3.13 (t, J 12.4 Hz, 1H) , 2.86 -2.71 (m, 1H) , 1.92 (t, J 13.3 Hz, 2H) , 1.83 -1.72 (m, 1H) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.43% | To a Biotage vial were added 2-chloro-4- iodonicotinonitrile (1.03 g, 3.90 mmol), 2,2-difluoro-5-aminobenzodioxole (710 mg, 3.90 mmol), bis(2-diphenylphosphinophenyl)ether (64 mg, 0.12 mmol), palladium(II) acetate (17 mg, 0.078 mmol), CS2CO3(1.777 g, 5.453 mmol), and dioxane (7.8 mL) and was stirred at rt while purging with N2stream for 30 min, then it was placed in heating block at 110 C for 1.5 h. Next, fert-butyl (3R)-3-[(2-sulfanylacetyl)amino]piperidine-1-carboxylate (Intermediate 22) (6.0 mL, 3.9 mmol) was added and it was purged with N2for 15 min, then was heated at 90 C for 1.5 hr. The reaction mixture was diluted with EtOAc, filtered through Celite, concentrated to dryness, and purified by flash column chromatography to give the title compound as a yellow oil (1.715 g, 80.43% yield). |
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