Structure of 624734-22-1
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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. : | 624734-22-1 |
Formula : | C7H2ClF3N2 |
M.W : | 206.55 |
SMILES Code : | FC(F)(F)C1=CC(C#N)=C(Cl)N=C1 |
MDL No. : | MFCD10697685 |
InChI Key : | BWFBFKPZLKQYPR-UHFFFAOYSA-N |
Pubchem ID : | 20071599 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.7 |
Solubility | 0.412 mg/ml ; 0.00199 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.47 |
Solubility | 0.701 mg/ml ; 0.00339 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.62 |
Solubility | 0.0495 mg/ml ; 0.00024 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 |
-6.09 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 |
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) |
2.15 |
* 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 |
---|---|---|
95% | Step E; To a suspension of NaH (7.8 g, 200 mmol) in tetrahydrofuran (100 mL) under nitrogen was added dropwise a solution of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (20 mL, 120 mmol) in anhydrous tetrahydrofuran (100 mL) via syringe. The reaction mixture was stirred for 0.5 h before a solution of the intermediate prepared in Step D, Intermediate 8 (20.1 g, 97.6 mmol) in tetrahydrofuran (200 mL) was added slowly via syringe. The reaction was stirred at room temperature overnight, then quenched with a saturated solution of NHtCl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 x). The combined organic layers were washed with water (3 x), dried over Na2S04, filtered, and evaporated i71 vacuo. Flash chromatography afforded 31.76 g (95percent) of the pure desired product. 1H NMR (500 MHz, CDCl3) 8 9.03 (d, J=1.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 5.25 (s, 1H), 3.86 (s, 3H), 1.52 (s, 9H). | |
95% | Step E; To a suspension of NaH (7.8 g, 200 mmol) in tetrahydrofuran (100 mL) under nitrogen was added dropwise a solution of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (20 mL, 120 mmol) in anhydrous tetrahydrofuran (100 mL) via syringe. The reaction mixture was stirred for 0.5 h before a solution of the intermediate prepared in Step D, Intermediate 8 (20.1 g, 97.6 mmol) in tetrahydrofuran (200 mL) was added slowly via syringe. The reaction was stirred at room temperature overnight, then quenched with a saturated solution of NH4Cl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 x). The combined organic layers were washed with water (3 x), dried over Na2S04, filtered, and evaporated in vacuo. Flash chromatography afforded 31.76 g (95percent) of the pure desired product. | |
95% | To a suspension of NaH (7.8 g, 200 mmol) in tetrahydrofuran (100 mL) under nitrogen was added dropwise a solution of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (20 mL, 120 mmol) in anhydrous tetrahydrofuran (100 mL) via syringe. The reaction mixture was stirred for 0.5 h before a solution of the intermediate prepared in Step D, Intermediate 11 (20.1 g, 97.6 mmol) in tetrahydrofuran (200 mL) was added slowly via syringe. The reaction was stirred at room temperature overnight, then quenched with a saturated solution of NH4Cl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3.x.). The combined organic layers were washed with water (3.x.), dried over Na2SO4, filtered, and evaporated in vacuo. Flash chromatography afforded 31.76 g (95percent) of the pure desired product. 1H NMR (500 MHz, CDCl3) delta 9.03 (d, J=1.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 5.25 (s, 1H), 3.86 (s, 3H), 1.52 (s, 9H). |
94.6% | To a suspension of NaH (7.8 g, 200 mmol) in THF (100 mL) under nitrogen was added dropwise a solution of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (20 mL, 120 mmol) in anhydrous THF (100 mL) via syringe. The reaction mixture was stirred for 0.5 h before a solution of the intermediate prepared in Step D (20.1 g, 97.6 mmol) in THF (200 mL) was added slowly via syringe. The reaction was stirred at room temperature overnight, then quenched with a saturated solution of NH4Cl. The organic layer was separated and the aqueous layer extracted with ethyl acetate (3.x.). The combined organic layers were washed with water (3.x.), dried over Na2SO4, filtered, and evaporated in vacuo. Flash chromatography afforded 31.76 g (94.6percent) of the pure desired product. 1H NMR (500 MHz, CDCl3) delta 9.03 (d, J=1.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 5.25 (s, 1H), 3.86 (s, 3H), 1.52 (s, 9H). | |
84% | To a suspension of sodium hydride (0.752 g, 29.8 mmol) in THF (18 mL) under nitrogen was added dropwise a solution of <strong>[42726-73-8]tert-butyl methyl malonate</strong> (3.18 mL, 17.9 mmol) in dry THF (15 mL) via syringe during a period of 15 min. The reaction mixture was stirred for 30 min before a solution of 2-chloro-5-(trifluoromethyl)nicotinonitrile (4.0 g, 14.5 mmol) in THF (30 mL) was added slowly. After being stirred at room temperature overnight, the reaction mixture was quenched with aqueous NH4Cl. THF was removed in vacuo and the aqueous solution was extracted with EtOAc three times. The combined organic layers were dried over MgSO4, filtered, and evaporated in vacuo. The crude brown product (7.1 g) was purified by flash chromatography (10:90 EtOAc/hexanes) to afford 4.20 g (84percent) of desired product as a yellow oil. LC-MS calculated for C15H15F3N2O4: (M+H)+345; found 245.0 (M-CO2tBu+H+1)+. |
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