Structure of 799557-86-1
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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. : | 799557-86-1 |
Formula : | C5H2BrF3N2 |
M.W : | 226.98 |
SMILES Code : | BrC1=CN=C(N=C1)C(F)(F)F |
MDL No. : | MFCD09754046 |
InChI Key : | GIFDWXWNFKZVEI-UHFFFAOYSA-N |
Pubchem ID : | 33697963 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.81 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.65 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.24 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.73 |
Solubility | 0.427 mg/ml ; 0.00188 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.97 |
Solubility | 2.43 mg/ml ; 0.0107 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.4 |
Solubility | 0.0908 mg/ml ; 0.0004 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 |
-6.4 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) |
1.48 |
* 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 |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 14h;Inert atmosphere; Sealed tube; | Example 68 2-[(4-Fluoro-benzenesulfonyl)-isopropyl-amino]-N-[3-(2-trifluoromethyl-pyrimidin-5-yl)- benzyl] -acetamide A solution of 3-[(teri-butoxycarbonylamino)methyl]phenylboronic acid (500 mg, 1.99 mmol), 5- bromo-2-(trifluoromethyl)pyrimidine (452 mg, 1.99 mmol) and potassium carbonate (0.28 g, 1.99 mmol) in DMF (5 mL) at 25C was purged with nitrogen gas and evacuated three times. The solution was then treated with teira/3's(triphenylphosphine)-palladium(0) (115 mg, 100 μιηο) and then sealed and heated to 120C for 14 h. The reaction mixture was cooled to 25 C, unsealed and poured into water. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. Filtration followed by concentration in vacuo gave [3-(2-trifluoromethyl-pyrimidin-5-yl)-benzyl]-carbamic acid teri-butylester (0.50 g, 71%) as a brown solid. MH+ = 354.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.2% | With n-butyllithium; In tetrahydrofuran; hexane; at -78℃; for 2.0h;Inert atmosphere; | To a solution of 5-bromo-2-(trifluoromethyl)pyrimidine (700.6 mg, 3.1mmol) and(iPrO)3B (1.1 mL, 4.7mmol) in THF (10 mL) was added dropwise n-BuLi (1.7 mL , 2.4M in hexane, 4.0 mmol) at -78oC. The mixture was stirred at the same temperature for 2 h and quenched with water. The solvent was removed under reduced pressure and the residue was extracted with Ether (2 x 40 mL). The aqueous layer was separated, then adjusted to pH 6 with 1N HCl and extracted with EA (3 x 40 mL). Combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the title product (400 mg, 67.2percent yield) as a white solid. Retention time (LC-MS): 0.66 min. MH+ 193 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35 g | 28 g of 5-bromo-2-trifluoromethylpyrimidine was added to 300 ml of tetrahydrofuran, and the temperature was lowered to -78 C. 120 ml of 2.5 M n-butyllithium was added dropwise, and the mixture was stirred for 1 hour, and 25 g of N-benzylpiperidine was added dropwise. The ketone in tetrahydrofuran solution was stirred for 3 hours, naturally warmed to room temperature, and a saturated aqueous solution of ammonium chloride was added dropwise, and water and ethyl acetate were separated to separate fractions. The organic phase was collected, dried, concentrated, and separated by column to obtain 35 g of 1-benzyl- 4-(2-Trifluoromethylpyrimidin-5-yl)piperidin-4-ol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29 g | With bromine; acetic acid;Reflux; | 24 g of 2-trifluoromethylpyrimidine was added to 200 ml of acetic acid, 50 g of bromine was added dropwise, and the mixture was heated under reflux overnight, cooled, water and ethyl acetate were added, and the mixture was separated, and the organic phase was collected, dried and concentrated to give 29 g. 5-Bromo-2-trifluoromethylpyrimidine. |
29 g | With bromine; acetic acid;Reflux; | Add 24g of 2-trifluoromethylpyrimidine to 200ml of acetic acid,50 g of bromine was added dropwise, and the mixture was stirred under heating and refluxed overnight.Cool, add water and ethyl acetate, extract the liquid,Collect the organic phase, dry, concentrate,29 g of 5-bromo-2-trifluoromethylpyrimidine were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Water (7 kg, 0.28 kg/kg compound 8B) as a solution in THF (22.4 kg, 0.88 kg/kg compound 8B) was added to the reaction product mixture with stirring while maintaining the temperature -55 to -65 C, and the reaction product mixture was held at that temperature for at least 30 minutes with stirring. The reaction product heated to 0 C over 1-2 hours and then water (376 kg, l3kg/kg compound 8B) was combined with the reaction product mixture while maintaining the temperature under 10 C and the reaction product mixture was maintained under those conditions for at least 30 minutes. The admixture was allowed to settle for at least 10 minutes and the bottom aqueous layer comprising compound 8 was removed. The aqueous layer was admixed with MTBE (93.2 kg, 3.7 kg/kg compound 8B) and stirred for at least 10 minutes. The admixture was allowed to settle for at least 10 minutes and the bottom aqueous layer comprising compound 8 was removed. The pH of the aqueous layer was adjusted to 1 to 2 at a temperature of less than 25C with concentrated The pH-adjusted aqueous phase was admixed with MTBE (93.2 kg, 3.7 kg/kg compound 8B) and stirred for at least 10 minutes. The admixture was allowed to settle for at least 10 minutes and the bottom aqueous layer was removed leaving an organic layer comprising compound 8. The aqueous layer was admixed with MTBE (93.2 kg, 3.7 kg/kg compound 8B) and stirred for at least 10 minutes, the admixture was allowed to settle for at least 10 minutes, and the bottom aqueous layer was removed. The aqueous layer was step was repeated and the aqueous layer was discarded. The organic layers were combined in a reactor and distilled under reduced pressure at a temperature of less than 45 C to reduce the volume to about 3 L/kg compound 8B. l,4-dioxane (130.16 kg, 5.17 kg/kg compound 8B) was charged to the reactor with stirring and the rector contents were distilled under reduced pressure to reduce the volume to about 3 L/kg compound 8B. The reactor contents were cooled to 25 C to yield a solution of compound 8 in l,4-dioxane (71.3 kg, 82% yield). The assay was determined to be 24.5 w/w % compound 8. |
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