Structure of 476342-37-7
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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. : | 476342-37-7 |
Formula : | C10H15N3O |
M.W : | 193.25 |
SMILES Code : | NC1=CC=C(N=C1)N1CCC(O)CC1 |
MDL No. : | MFCD09728697 |
InChI Key : | JFSQCTGGZLCLFF-UHFFFAOYSA-N |
Pubchem ID : | 16781994 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 59.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.38 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.27 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.38 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.56 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.6 |
Solubility | 4.81 mg/ml ; 0.0249 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.38 |
Solubility | 8.06 mg/ml ; 0.0417 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.59 |
Solubility | 4.99 mg/ml ; 0.0258 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 |
No |
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 |
-7.12 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) |
2.26 |
* 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 |
---|---|---|
89% | With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 3.0h; | Example 18C. l-(5-Aminopyridin-2-yl)piperidin-4-ol [00153] A solution of l-(5-nitropyridin-2-yl)piperidin-4-ol (Example, 18B, 0.6g, 2.6 mmol) in ethanol was added 10% palladium on carbon (0.3 g) and the mass was stirred at RT with hydrogen bladder for 3 h. Reaction mass was filtered through CELITE and concentrated to remove ethanol to yield Example 18C (0.45 g, 89% yield) as a brown oil. LC-MS, [M+H]+ = 194. 1U NMR (CD3OD, 400MHz): delta 7.70 (d, J = 2.6 Hz, IH), 7.10 (dd, J = 2.6, 8.8 Hz, IH), 6.73 (d, J = 8.8 Hz, IH), 3.76 (m, 3H), 2.91 (m, 2H), 1.89 (m, 2H), 1.51 (m, 2H). |
51% | With hydrogenchloride; iron; In ethanol; water; at 90℃; for 2.0h; | To a suspension of 1.35g (6.04mmol) of the compound obtained in the Manufacturing Example 73 in 18mL of ethanol and 3mL of water were added 1.3g of reduced iron and 0.25mL of conc. hydrochloric acid, and the mixture was stirred for 2 hours at 90C. After cooling the reaction mixture, the mixture was filtrated by Celite and filtrate was condensed under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol = 10/1) to give 601mg (51%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 5.0h; | General procedure: 10%) Palladium on carbon (0.095g) was added to a solution of 3'- fluoro-3 -nitrobiphenyl (L) (0.63 g, 2.88 mmol) in EtOH (20.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 5 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography using a 40 g Thomson normal phase silica gel cartridge (100% hexanes ? 15:85 EtOAc:hexanes) to afford 3'-fluoiObiphenyl-3-amine (LI) (0.34 g, 1.81 mmol, 63% yield) as a light yellow oil. 1H NMR (DMSO-d6) delta ppm 7.47-7.44 (m, 1H), 7.40- 7.39 (m, 1H), 7.36-7.33 (m, 1H), 7.15-7.14 (m, 1H), 7.10 (t, J=7.7Hz, 1H), 6.85-6.84 (m, 1H), 6.80-6.79 (m, 1H), 6.60-6.58 (m, 1H), 5.18 (s, 2H); ESIMS found for C12H10FN mlz 188 (M+H). |
99.5% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 6.0h; | General procedure: Step 2 10% Palladium on carbon (40 mg) was added to a solution of 1-methyl-4-(5-nitropyridin-2-yl)piperazine (LIX) (3.80 g, 17.09 mmol) in EtOH (50.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 6 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure to afford 6-(4-methylpiperazin-1-yl)pyridin-3-amine (LX) as a brown viscous oil which solidified under vacuum (3.30 g, 17.1 mmol, quantitative). |
99.5% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 6.0h; | General procedure: 10% Palladium on carbon (0.095g) was added to a solution of 3'-fluoro-3- nitrobiphenyl (L) (0.63 g, 2.88 mmol) in EtOH (20.0 mL). The flask was evacuated and replaced with a hydrogen atmosphere. The solution was stirred at room temperature for 5 h under hydrogen. The catalyst was filtered through a pad of Celite, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography using a 40 g Thomson normal phase silica gel cartridge ( 100% hexanes? 15 : 85 EtOAc:hexanes) to afford 3'-fluorobiphenyl-3-amine (LI) (0.34 g, 1.81 mmol, 63% yield) as a light yellow oil. |
Preparation of 5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-ol With a method similar to that used for the preparation of 6-morpholin-4-yl-pyridin-3-ylamine above, 5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-ol was prepared from 2-chloro-5-nitro-pyridine and piperidin-4-ol. LCMS calcd for C10H15N3O (m/e) 193, obsd 194 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 18D. 4-(4-Chlorophenyl)- 1 -((dimethylamino)methyleneamino)-N-(6-(4- hydroxypiperidin- 1 -yl)pyridin-3-yl)- lH-pyrrole-2-carboxamide[00154] To a mixture of 5-(4-chlorophenyl)-2-(dimethylamino-methyleneamino)- 2H-pyrazole-3-carboxylic acid (Example 18A, 0.175 g, 0.59mmol) and DMF (2 mL) was added EtaOBT (0.039g, 0.3mmol), EDCI HCl (0.33 g, 1.7mmol) and DIPEA (0.15g, 1.18mmol). The resulting mixture was stirred at room temperature for 15 min. Example 18C was then added and the mixture was stirred at room temperature overnight. Reaction mass was quenched into water, solid obtained was filtered and washed with water. Pale brown solid (Example 18D, 0.1 g, 37% yield) obtained was taken to the next step without purification. LC-MS, [M+Eta]+ = 467. |
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