Structure of 20274-69-5
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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. : | 20274-69-5 |
Formula : | C7H6FNO3 |
M.W : | 171.13 |
SMILES Code : | OCC1=CC(=C(F)C=C1)[N+]([O-])=O |
MDL No. : | MFCD01861396 |
Boiling Point : | No data available |
InChI Key : | MKWJZTFMDWSRIH-UHFFFAOYSA-N |
Pubchem ID : | 4167587 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.75 |
Solubility | 3.04 mg/ml ; 0.0178 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.94 |
Solubility | 1.94 mg/ml ; 0.0114 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.88 |
Solubility | 2.25 mg/ml ; 0.0131 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 |
-6.66 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 |
2.0 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) |
1.74 |
* 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 |
---|---|---|
50.2% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 70℃; | Intermediate 163: (3-nitro-4-((tetrahydro-2H-pyran-4-yl)amino)phenyl)methanol A round bottom flask was charged with (4-fluoro-3-nitrophenyl)methanol (1 g, 5.84 mmol), tetrahydro-2H-pyran-4-amine, hydrochloride (0.9 g, 6.54 mmol, J&W PharmLab), DMF (10 mL) and DIPEA (4.1 mL, 23.48 mmol). An air condensor was fitted and the slurry warmed to 70C overnight. The mixture was cooled to room temperature, diluted with EtOAc and the organics washed with 1M HCl followed by brine before being passed through a hydrophobic frit. The filtrate was concentrated in vacuo to give an orange oil. The sample was loaded in dichloromethane and purified by silica gel column chromatography (50g silica) using a gradient of 0-100percent ethyl acetate-cyclohexane over 15 CV. The appropriate fractions were combined and evaporated in vacuo to give an orange oil. The sample was dissolved in EtOAc before being washed with 10percent LiCl solution. the organics were passed through a hydrophobic frit before being concentrated in vacuo to give the title compound (740 mg, 2.93 mmol, 50.2 percent yield) as an orange solid. LCMS (System A): tRET = 0.71 min, MH+ = 253. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With N-ethyl-N,N-diisopropylamine; In 2-methyltetrahydrofuran; at 80℃; | Intermediate 84: (S)-tert-butyl 3-(((4-(hydroxymethyl)-2- nitrophenyl)amino)methyl)piperidine-1-carboxylate DIPEA (7.65 mL, 43.8 mmol) was added to a stirred solution of 4-Fluoro-3-nitrobenzyl alcohol (2.50 g, 14.61 mmol) and (3S)-3-(aminomethyl)piperidine (4.70 g, 21.91 mmol in 2-Methyltetrahydrofuran (15 mL). The solution was heated to 80 oC ovenight , the reaction mixture cooled to room temperature and the resulting solid partitioned between EtOAc and sat. aq. NaHCO3. The aqueous layer was removed and the organic layer washed (1x sat. aq. NaHCO3, 1x brine). The organic portion was dried over MgSO4 and evaporated in vacuo to an orange oil. The residue was dissolved in DCM and purified by silica gel chromatography eluting with cyclohexane:EtOAc (10 - 66%). The product containing fractions were evaporated in vacuo to an orange oil foam. The oil was dissolved in TBME and evaporated in vacuo to an orange oil to give the title compound as an orange oil (5.52 g). The total yield of the reaction was 88%. LCMS (System C): tRET = 1.27 min, MH+ = 366. |
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