Structure of 171366-19-1
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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. : | 171366-19-1 |
Formula : | C6H5FINO |
M.W : | 253.01 |
SMILES Code : | OCC1=C(I)C=CN=C1F |
MDL No. : | MFCD03095295 |
InChI Key : | FQCZQIGAGKWNEA-UHFFFAOYSA-N |
Pubchem ID : | 11021396 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.04 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.59 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.6 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.45 |
Solubility | 0.901 mg/ml ; 0.00356 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.34 |
Solubility | 11.7 mg/ml ; 0.0461 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.09 |
Solubility | 0.206 mg/ml ; 0.000815 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 |
-7.1 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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.83 |
* 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 |
---|---|---|
77% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; | Preparation 45; 2-Fluoro-4-iodo-3-methoxymethoxymethyl-pyridine; Add chloromethyl methyl ether (2 g, 25.0 mmol) gradually to a solution of 2-fluoro- 4-iodo-pyridin-3-yl)-methanol (1.0 g, 3.95 mmol) and N, N-diisopropylethylamine (5 g, 39 mmol) in dichloromethane (5 mL). Stir the mixture at room temperature overnight. Dilute the mixture with chloroform. Wash the organic layer with saturated aqueous sodium chloride and water. Dry the mixture over sodium sulfate. Concentrate the solution in vacuo to a brown oil. Purify by column chromatography (10 % methanol in dichloromethane) to afford the title compound (0.90 g, 77 %) as yellow oil. MS (ES) m/z 298 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
708 mg (62%) | With n-butyllithium; sodium borohydrid; diisopropylamine; In tetrahydrofuran; ethyl acetate; | EXAMPLE 1 2-Fluoro-4-iodo-3-(hydroxymethyl)pyridine To a solution of LDA, freshly prepared from diisopropylamine (0.63 mL, 4.49 mmol) and n-BuLi (4.49 mmol) in THF (10 mL) at -78 C., is cannulated a solution of 2-fluoro-3-iodopyridine (1 g, 4.48 mmol) in 2 mL of THF, and the mixture is stirred for 1 hour at -78 C. under nitrogen. Ethyl formate (1.1 mL, 13.6 mmol) is added to the reaction mixture at -78 C. and stirring is continued for 30 min. The reaction is quenched with saturated sodium bicarbonate solution at -78 C. and allowed to warm to room temperature. Sodium borohydride (0.34 g, 8.99 mmol) is slowly added to the reaction mixture and then stirred for 30 min. The mixture is extracted with ethyl acetate. The combined ethyl acetate extracts are washed with brine, dried (MgSO4) and concentrated in vacuo. The residue is purified by radial plc (silica gel, hexanes, 10% EtOAc/hexanes, 20% EtOAc/hexanes) to afford 708 mg (62 %) of the product as a white solid having a mp of 69-70 C. Elemental Analysis for C6 H5 FINO: theory: C 28.48, H 1.99, N 5.54; found: C 28.55, H 1.94, N 5.48. IR (KBr): cm1 3336, 1584, 1541, 1446, 1401, 1264, 1218, 1003, 870, 833,803,761,577. 1 H NMR (CDCl3): delta7.79-7.82 (d, 1H,J=5 Hz), 7.66-7.68 (d, 1H, J=5 Hz), 4.82-4.86 (d, 2H, J=7 Hz), 1.99-2.04 (t, 1H, J=14 Hz). 13 C NMR (CDCl3): delta 162.29, 159.05, 147.30, 147.09, 132.79, 132.73,126.14, 125.73, 114.21, 62.24. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1H-imidazole; tert-butyldimethylsilyl chloride; In dichloromethane; at 20.0℃; for 1.0h; | [00344] 3-(((tert-Butyldimethylsilyl)oxy)methyl)-2-fluoro-4-iodopyridineTo a solution of <strong>[171366-19-1](2-fluoro-4-iodopyridin-3-yl)methanol</strong> (3.52 g, 13.91 mmol) in CH2CI2 (80 mL) at room temperature was sequentially added imidazole (1.894 g, 27.8 mmol) and TBDMS-C1 (2.52 g, 16,69 mmol). The reaction was stirred at room temperature for 1 h before diethylether was added and the insoluble salts were filtered. Silica gel was added to the filtrate prior to the solvent removal under vacuum. The dry silica gel was packed, and the adsorbed product was purified by flash chromatography (hexane/EtOAc 10:0 to 7:3) to give 3-(((ieri-butyldimethylsilyl)oxy)methyl)-2-fluoro-4-iodopyridine as a white solid (4.5 g). LC/MS m/z 368 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00343] (2-Fluoro-4-iodopyridin-3-yl)methanol F OH. To a solution of 2-fluoro-4- iodonicotinaldehyde (3.50 g, 13.94 mmol) in absolute EtOH (56 mL) was added sodium borohydride (0.264 g, 6.97 mmol) at room temperature. The reaction was stirred at room temperature for 1 h, followed by the slow addition of 1 M aqueous hydrochloric acid. The product was extracted with CH2CI2 (repeated four times), and the organic layers were combined, dried over sodium sulfate, filtered and concentrated to dryness. The aqueous phase was basified to pH 8-10 with 2 M aqueous sodium hydroxide and extracted with diethylether (repeated four times). Then the organic layers were combined, dried over sodium sulfate, filtered, combined with the previously obtained residue and concentrated to dryness under vacuum. The residue was used without any purification in the next step. LC/MS m/z 254[M+H]+. |
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