Structure of 401930-07-2
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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. : | 401930-07-2 |
Formula : | C10H12F3N3O |
M.W : | 247.22 |
SMILES Code : | OC1CCN(C2=NC=CC(C(F)(F)F)=N2)CC1 |
MDL No. : | MFCD01311906 |
InChI Key : | QQWTYVSELDRYPM-UHFFFAOYSA-N |
Pubchem ID : | 2795837 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.6 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 57.64 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.42 |
Solubility | 0.95 mg/ml ; 0.00384 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.09 |
Solubility | 2.01 mg/ml ; 0.00813 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.46 |
Solubility | 0.849 mg/ml ; 0.00344 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) |
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 |
-6.78 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) |
2.55 |
* 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 |
---|---|---|
3.89 g | With triethylamine; In isopropyl alcohol; for 5.0h;Reflux; | Piperidin-4--ol (1.65 g, 16.3 mmol), 2-chioro-4-(trifluoromethyl)pyrimidine (2.98 g,16.3 mmoi), and triethylamine (4.5 mL, 32.7 mmol) were refluxed in isopropanol (60 mU) for 5h. The reaction was cooled to room temperature and diluted with hexanes causing a white precipitate to fOrm. The solids were removed by filtration, and the filtrate was passed through a plug of silica, washing with 1: 1 EtOAc/hexanes and then EtOAc, The combined filtrate and washings were concentrated to dryness to afford 3,89 g of the title compound. Exact mass calculated for C,0H7F3N,O: 247,09, found: LCMS rn/a = 248.2 [M±H1*. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium tert-butylate; In tetrahydrofuran; at 0 - 20℃; for 0.5h; | To a solution of I -(4-(trit1uorometIYy1)pyTitnidin-2-ypiperidin-4-ol (1.01 g, 4,08 rarnol) and 4,6-diehloro-5-rnethylpyrimidine (0.66 g, 4,08 rnrnoi) in TI-IF (15 mE) was added potassium tert-butoxide (0.50 g, 4.48 mmol) portior-wise at 0 C. The reaction was then stirredat room temperature for 30 nin, The crude reaction mixture was partitioned between EtOAc/I-{20. The organic layer was dried over MgSO4, fihered, and concentrated, The residue was purified by Biotage column chromatography (0-100% EtOAc/Hex in 30 mm) to give the title compound (1.40g. 3.73 mmoi, 92%). Exact mass calculated for C,5H,5C1F3N50: 373.1, found LCMS rn/a = 374.2 [M÷Hj?. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.07 g | With potassium tert-butylate; In tetrahydrofuran; at 0 - 20℃; for 1.0h; | Potassium 2-niethylpropan-2-olate (17.3 niL, 17.3 mmol) was added to a solution of 1- (4-(irifiuoromethyl)pyrimidin-2--yl)piperidin-4-ol (3.89 g, 15.7 mmoi) and 4,6-dichioro--5- methoxypyrimidinc (2.82 g, 15.7 mmol) in THF (58 mL) at 0 C. The reaction was warmed toroom temperature and stirred fOr I Iv The reaction was concentrated to a yellow solid and triturated with EtOAc and hexanes to afford 6.07 g of the tide compound. Exact mass calculated for C,1H,5CIF,N501?. 38909, found: LCMS rn/a = 390.4 [M+H]?; ?H NMR (400 MHz, CDCI3) S ppm I .86-1.96 (m, 2H), 2,08-2,17 (in, 21-1), 3.75-3.84 (in. 2Fl), 3.92 (s, 3H), 4.21-4.29 (m. 21-1), 5.50 (septet, J= 3.8 Fiz, 11-1). 6.77 (d, .J= 4,8 1-lz, lFl). 8.29 (s, 11-1), 8,50 (d,,J= 4.8 Flz, 1H). |
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