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Structure of 1-Fluoro-2-iodoethane
CAS No.: 762-51-6
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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. : | 762-51-6 |
Formula : | C2H4FI |
M.W : | 173.96 |
SMILES Code : | ICCF |
MDL No. : | MFCD00748131 |
InChI Key : | LVYJIIRJQDEGBR-UHFFFAOYSA-N |
Pubchem ID : | 69804 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P210-P233-P240-P241+P242+P243-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P403+P235-P501 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅱ |
Num. heavy atoms | 4 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 24.74 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.91 |
Solubility | 2.14 mg/ml ; 0.0123 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.29 |
Solubility | 8.83 mg/ml ; 0.0508 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.92 |
Solubility | 2.12 mg/ml ; 0.0122 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-6.17 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 |
3.0 |
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) |
2.92 |
* 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 |
---|---|---|
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 18h; | To a solution of 4-chloro-3-hydroxy-benzoic acid (1.04 g, 6.03 mmol, 1.0 equiv) in anhydrous DMF (12 mL) under Ar was added K2CO3 (2.08 g, 15.07 mmol, 2.5 equiv) and 1-fluoro-2-iodo-ethane (3.67 g, 21.09 mmol, 3.5 equiv) and the mixture stirred at 50 C. for 18 h. The reaction mixture was poured on ice, extracted with ethyl acetate (2×100 mL) and the combined organic phases washed with water (2×100 mL). The organic phase was dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude reaction product purified with column chromatography on silica eluting with hexane/ethyl acetate (1:3) to give 1.57 g (98%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Intermediates 72 and 73Ethyl 1-(2-fluoroethyl)-1H-pyrazole-5-carboxylate and ethyl 1-(2-fluoroethyl)-1H- pyrazole-3-carboxylate To a solution of ethyl 1 H-pyrazole-3-carboxylate (0.77g) (available from ABCR) in acetonitrile (30ml) was added cesium carbonate (1.79g) and the mixture stirred for 5min when 1-fluoro-2-iodoethane (0.96g) was added and the mixture stirred at 200C for 18h.The mixture was evaporated and the residue taken up in water (30ml) and DCM (30ml) separated by hydrophobic frit and concentrated to ~5ml, placed on an SPE cartridge (5Og silica) and eluted with a gradient of ethyl acetate in cyclohexane to give the Ethyl 1-(2- fluoroethyl)-1 H-pyrazole-5-carboxylate (0.42g) as a colourless oil.LC/MS R1 2.09 min m/z 186 [MH+]. Method C and ethyl 1-(2-fluoroethyl)-1 H-pyrazole-3-carboxylate (g) as a colourless oilLC/MS R1 1.73 min m/z 186 [MH+]. Method C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.69 g | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | Step A: 2-bromo-5-(2-fluoroethoxy)benzonitrile. To <strong>[189680-06-6]2-bromo-5-hydroxybenzonitrile</strong> (1.5 g, 7.6 mmol) in DMF (5 mL) was added Cs2CO3 (3.7 g, 11.4 mmol) and 1-iodo-2-fluoroethane (1.23 mL, 15.1 mmol) and the mixture was left to stir at room temperature. Upon completion the reaction mixture was diluted with H2O and the aqueous layer extracted with EtOAc (3*). The combined organics were washed with 5% LiCl solution, brine, dried with MgSO4, filtered and concentrated. Purification via silica gel chromatography (0-30% EtOAc in hexanes) gave the title compound (1.69 g) as a light yellow oil. 1H NMR (500 MHz, Chloroform-d) delta 7.56 (d, J=8.9 Hz, 1H), 7.18 (d, J=3.0 Hz, 1H), 7.05 (dd, J=8.9, 3.0 Hz, 1H), 4.87-4.63 (m, 2H), 4.30-4.14 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.6% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | To a mixture of 2- chloropyrimidin-5-ol (1 g, 7.6 mmol) and i-fluoro-2-iodoethane (1.73 g, 9.9 mmol) in DMF (2.9 mL) was added 052003 (3.2 g, 9.9 mmol). The mixture was stirred vigorously for 3 h. The reaction mixture was diluted with EtOAc (20 mL) and filtered, and the solid was washed with EtOAc (20 mL). Thefiltrate was washed with water (3x30 mL) and dried (Na2504) and concentrated. Purification (FCC, 5i02, DCM/EtOAc) afforded the title compound as a white solid (847 mg, 62.6percent). MS (ESI): mass calcd. for C5H5CIFN2O, 176.0; m/zfound, i7i.i[M+H]. |
27% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h; | Step A: 2-chloro-5-(2-fluoroethoxy)pyrimidine. To a vial charged with <strong>[4983-28-2]2-chloropyrimidin-5-ol</strong> (300 mg, 2.23 mmol) and Cs2CO3 (0.97 g, 3.0 mmol), was added 1-fluoro-2-iodoethane (480 mg, 2.76 mmol) in DMF (5 mL). The mixture was stirred vigorously at rt for 3, then diluted with water, extracted with EtOAc, washed with brine. The organic layers were dried and concentrated. The residue was purified on a silica gel chromatography to afford 2-chloro-5-(2-fluoroethoxy)pyrimidine (111 mg, Yield 27percent). MS (ESI): mass calcd. for C5H6ClFN2O, 176.0; m/z found, 177.0 [M+H]+. 1H NMR (400 MHz, d-chloroform) delta 8.31-8.24 (s, 2H), 4.80-4.74 (m, 1H), 4.70-4.64 (m, 1H), 4.31-4.20 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | To a solution of <strong>[1025718-84-6]3-bromo-5-(trifluoromethyl)phenol</strong> (500 mg, 2.1 mmol) in DMF (3.2 mL) was added potassium carbonate (573 mg, 4.1 mmol).1-fluoro-2-iodoethane was added dropwise at rt. The reaction was stirred overnight. The reaction mixture was diluted with EtOAc (50 mL) and brine (30 mL). The organic layer was collected, dried over Na2SO4 and concentrated. The residue was purified (FCC EtOAc in Hexanes 0% to 50%) to afford colorless oil (380 mg, yield 64%) MS (ESI): mass calcd. for 286.0; m/z found, 287.1 [M+H]+.1H NMR (400 MHz, CDCl3) delta 7.43 (d, J = 0.7 Hz, 1H), 7.38- 7.24 (s, 1H), 7.15 (d, J = 0.7 Hz, 1H), 4.92- 4.69 (m, 2H), 4.37- 4.24 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.1 g | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; | To a solution of <strong>[610-37-7]5-hydroxy-2-nitrobenzoic acid</strong> in a 100 mL RBF (3.50 g, 19.11 mmol) in DMF (22 mL) was added powered K2C03(5.28 g, 38.23 mmol). Then 1- fluoro-2-iodoethane (13.9 g, 81.91 mmol, 8.0 mL) was added to the mixture. The reaction mixture was heated at 80 C overnight. Then the reaction was checked by LC-MS. The product doesn't ionize well. There were 3 major peaks, one of which corresponded to the starting acid, another corresponding to the desired product (the largest of the 3) and a third peak presumed to be a monoalkylated intermediate. The mixture was heated at 90 C for 3 d after which LC-MS showed there was one peak which corresponded to the desired product. The mixture was cooled to rt and poured into EtOAc then it was diluted with water. The biphasic mixture was shaken in a sep funnel and the aqueous layer was separated. The aqueous layer was then extracted twice more with EtOAc. The combined organic layers were washed twice with saturated NaCl, dried over sodium sulfate, decanted from the drying agent, and concentrated in vacuo to give 6.10 g, 116%, of a yellow oil. |