Structure of 886498-98-2
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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. : | 886498-98-2 |
Formula : | C9H8F2O3 |
M.W : | 202.16 |
SMILES Code : | FC1=C(C(=CC(=C1)OC)F)CC(=O)O |
MDL No. : | MFCD04115927 |
InChI Key : | KXWRAINJKJTUDG-UHFFFAOYSA-N |
Pubchem ID : | 5187379 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.74 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.56 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.2 |
Solubility | 1.29 mg/ml ; 0.00638 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.15 |
Solubility | 1.44 mg/ml ; 0.00713 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.87 |
Solubility | 0.274 mg/ml ; 0.00136 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 |
-6.43 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 |
0.56 |
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) |
1.64 |
* 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 |
---|---|---|
92% | With hydrogenchloride; In water;Heating; Reflux; | Methyl 2-(2,6-difluoro-4-methoxyphenyl)acetate (PMW04141)A solution of PMW04140 (3.37 g, 16.7 mmol) in MeOH (70 mL) containing cone. HCl (15 drops) was heated at reflux overnight. The mixture was allowed to cool and was neutralised with sat. aq. NaHCO3. The solvent was removed in vacuo and the residue was dissolved in EtOAc (100 mL) and washed with H2O (100 mL), sat. aq. NaHCO3 (100 mL) and brine (100 mL) then dried (MgSO4) and the solvent was removed in vacuo. The title compound (3JO g, 92%) was obtained as a pale yellow oil; 1H NMR (270 MHz, DMSO-de) 3.61 (2H, s, CH2), 3.69 (3H, s, CH3), 3.76 (3H, s, CH3), 6,40-6 49 (2H, m, ArH); 19F NMR (376.4 MHz, DMSO-d6) 414.4 (d); HRMS (ES+) calcd, for Ci0HnF2O3 (M++H) 217.0657, found 217.0663; LC/MS (ES+) tr = 1.69 min, m/z 216.8 (M+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | at 160℃; | 2- (2,6-Difluoro-4-methoxyphenyl)acetic acid (PMW04140)PMW04138 (4,49 g, 18.3 mmol) was heated at 160 0C until melting was complete and fizzing had ceased. Following cooling, the product was recrystallised from PE/EtOAC to give the title compound as a white crystalline solid (3.43 g, 93%); mp 137-139 0C; 1H NMR (270 MHz, DMSO-d6) 3,52 (2H, s, CH2), 3.77 (3H, s, CH3), 6.68-6,79 (2H, m, AiH); HRMS (ES+) calcd. for C9H9F2O2 203.0514, found 203.0508. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With boron tribromide; In dichloromethane; at 0 - 20℃; for 2.5h; | To a stirred solution of <strong>[886498-98-2](2,6-difluoro-4-methoxyphenyl)acetic acid</strong> (1.50 g, 7.42 mmol) in 20 ml anhydrous dichloromethane at 0C was added a solution of boron tribromide (4.29 ml, 44.5 mmol) in 10 ml anhydrous dichloromethane. The cooling bath was removed and the mixture allowed to warm to RT for 2 hours. The reaction was diluted with 20 ml anhydrous methanol, and stirred for 30 minutes. The mixture was concentrated under reduced pressure, and the residue purified by column chromatography on silica gel, (Biotage column, 50 g) using a gradient eluent of 0-30% ethyl acetate in hexanes (700 ml) to afford the title compound. 1H NMR (CDC13): delta 6.30 (d, J = 8.3 Hz, 2H), 6.12 (br, 1H), 3.76 (s, 3H), 3.63 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; acetic acid; at 100℃; | To a solution of the methyl ether (2.0 g, 9.9 mmol) in AcOH (10 mL) was added HBr(10mL).Then the mixture was stirred at 100 C over night. Then the reaction mixture was15 concentrated to give the desired product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; | To a stirred suspension of tert-butyl piperazine-1-carboxylate (1 g, 5.37 mmol), <strong>[886498-98-2]2-<strong>[886498-98-2](2,6-difluoro-4-methoxyphenyl)acetic acid</strong></strong> (45a) (1.09 g, 5.37 mmol; CAS 886498-98-2), EDC (1.24 g, 6.44 mmol), in acetonitrile (15 mL) and DMF (1 mL) was added TEA (2.25 mL, 16.11 mmol) and DMAP (33 mg, 0.27 mmol) and stirred at room temperature for 16 h. The reaction was concentrated to remove acetonitrile and diluted with ethyl acetate (100 mL), washed with IN KHSO4 (2 x 20 mL), saturated sodium bicarbonate (2 x 20 mL), water (20 mL), brine (20 mL), dried and concentrated to afford tert-butyl 4-(2-(2,6-difluoro-4-methoxyphenyl)acetyl)piperazine-1-carboxylate (45b) (1.00 g, 50 % yield) as a colorless solid;H NMR (300 MHz, DMSO-i%) delta 6.72 (s, 1H), 6.69 (d, J= 1.4 Hz, 1H), 3.77 (s, 3H), 3.66 (s,2H), 3.57 (t, J= 5.3 Hz, 2H), 3.49 - 3.24 (m, 6H), 1.41 (s, 9H); MS (ES+): 393.5 (+Na) (ES-): 369.3 (M-l). |
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