Structure of 50534-42-4
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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. : | 50534-42-4 |
Formula : | C6H16Cl2N2 |
M.W : | 187.11 |
SMILES Code : | CN(C)C1CNCC1.[H]Cl.[H]Cl |
MDL No. : | MFCD13561578 |
InChI Key : | LCPKWRSLMCUOOZ-UHFFFAOYSA-N |
Pubchem ID : | 22120278 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.38 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.96 |
Solubility | 2.05 mg/ml ; 0.0109 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.56 |
Solubility | 5.11 mg/ml ; 0.0273 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.86 |
Solubility | 25.6 mg/ml ; 0.137 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 |
-6.28 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 |
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) |
1.81 |
* 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 |
---|---|---|
61% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 140.0℃; for 0.5h;Microwave irradiation; | (3R)-N,N-Dimethylpyrrolidin-3-amine dihydrochloride (90 mg, 0.48 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 200 mg, 0.48 mmol) and DIPEA (0.250 mL, 1.45 mmol) in DMA (3 mL). This mixture was heated at 140C in a microwave for 0.5h. The mixture was then diluted with CH3OH and absorbed onto an SCX column, washed with CH3OH and eluted with 1:1 methanolic ammonia in CH2Cl2. Fractions containing the product were combined and concentrated in vacuo. Purification by FCC, eluting with 1.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (149 mg, 61%) as an orange foam; 1H NMR: 1.76-1.89 (1H, m), 2.14-2.25 (7H, m), 2.69-2.84 (1H, m), 3.12-3.27 (3H, m), 3.41-3.53 (1H, m), 3.89 (3H, s), 6.56 (1H, s), 7.13 (1H, td), 7.26-7.38 (1H, m), 8.06 (1H, s), 8.40-8.43 (2H, m), 8.73 (1H, s), 8.85 (1H, d), 8.95 (1H, s); m/z: ES+ MH+ 509.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.5% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A solution of N(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)-N-phenylethenesulfonamide(0.100 g, 0.255 mmol), <strong>[50534-42-4](R)-(+)-3-(dimethylamino)pyrrolidine dihydrochloride</strong> (0.096 g, 0.511 mmol) and N-,N-diisopropylethylamine (0.176 mL, 1.022 mmol) in dichloromethane (5 mL) was stirred at the room temperature for 18 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. Theorganic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 12 g cartridge; methanol / dichloromethane = 3 % to 5 %) to give (R)-N-(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)-2-(3-(dimethylamino)pyrro lidin-1-yl)-N-phenylethane-1-sulfonamide as white solid (0.082 g, 63.5 %).?H NMR (700 MHz, CDC13) oe 8.00 (d, 2 H, J = 8.5 Hz), 7.44 (d, 2 H, J = 8.5 Hz),7.33 - 7.24 (m, 5 H), 6.90 (t, 1 H, J= 51.7 Hz), 4.96 (s, 2 H), 3.28 (t, 2 H, JJ= 7.5Hz), 3.05 - 2.98 (m, 2 H), 2.97 - 2.90 (m, 2 H), 2.78 - 2.59 (m, 2 H), 2.47 (m, 1 H),2.27 (s, 6 H), 2.06 - 1.98 (m, 1 H), 1.79 (m, 1 H) ; LRMS (ES) mlz 506.4 (M÷+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 80.0℃; | 1-Fluoro-4-nitro-2- (trifluoromethyl) benzene(300 mg, 1.4 mmol), (R) - (+) - 3-dimethylaminopyrrolidine dihydrochloride(261 mg, 1.4 mmol) was dissolved in acetonitrile (20 mL) and potassium carbonate (387 mg, 2.8 mmol) was added. The reaction system at 80 C overnight, then allowed to cool. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3 x 20 mL). The organic phase is collected, dried over Na2SO4, filtered and concentrated to dryness. The crude title compound (320 mg) was used as a yellow solid for the next reaction. |
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