Structure of 24167-56-4
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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. : | 24167-56-4 |
Formula : | C9H10FNO |
M.W : | 167.18 |
SMILES Code : | O=C(N(C)C)C1=CC=C(F)C=C1 |
MDL No. : | MFCD01214152 |
InChI Key : | NUOGEPIJFRZXIN-UHFFFAOYSA-N |
Pubchem ID : | 141077 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.95 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.27 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.81 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 2.64 mg/ml ; 0.0158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.11 |
Solubility | 13.0 mg/ml ; 0.0778 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.73 |
Solubility | 0.313 mg/ml ; 0.00187 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) |
Yes |
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 |
-6.55 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) |
1.0 |
* 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 |
---|---|---|
70% | With 1-fluoro-2,4,6-trimethylpyridinium hexafluorophosphate; (tBuCN)2Cu*OTf; silver fluoride; In tetrahydrofuran; at 80℃; for 18h;Inert atmosphere; | General procedure: To an oven-dried 4 mL vial was added AgF (25 mg, 0.2 mmol, 2.0 equiv), ('BuCN^CuOTf (76 mg, 0.2 mmol, 2.0 equiv), [Me3pyF]PF6 (86 mg, 0.3 mmol, 3.0 equiv) and THF (2.0 mL). The aryl boronate ester (0.1 mmol, 1.0 equiv) was added (solid aryl boronate esters were weighed in the vial prior to adding THF, and liquid aryl boronate esters were added neat by syringe after the addition of THF). The vial was sealed with a Teflon- lined cap and heated at 50 C with vigorous stirring for 18 h. The solution was allowed to cool to room temperature, and 11.0 mu^ (0.1 mmol, 1.0 equiv) of 1 -bromo-4-fluorobenzene was added as an internal standard. The crude reaction mixture was analyzed by 19F NMR spectroscopy to determine the yield of aryl fluoride. 19F NMR chemical shifts were compared to authentic samples of the aryl fluoride product to confirm the identity of the product, and the identities of the products were further assessed by GC/MS.; cReactions were conducted at 80 C. |
The procedure of Example IA is followed substituting the following N,N-dimethyl aryl carboxamides for 4-methyl-N,N-dimethylbenzamide: 4-chloro-N,N-dimethylbenzamide; N,n-dimethyl-4-fluorobenzamide; N,n-dimethyl-4-methoxybenzamide; N,n-dimethyl-4-trifluoromethyl benzamide; N,n-dimethyl-2-thienylcarboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With sodium acetate; trichlorophosphate; In water; 1,2-dichloro-ethane; | EXAMPLE 10 Preparation of 2-(methylthio)-5-(4-fluorobenzoyl)pyrrole (Step 2) A solution of <strong>[24167-56-4]N,N-dimethyl-4-fluorobenzamide</strong> (8.4 g, 0.05 moles) in anhydrous 1,2-dichloroethane (170 ml) containing phosphorous oxychloride (7.7 g, 0.05 moles) was heated at reflux temperature for 1 hour. At the end of this time 2-methylthiopyrrole (2.82 g, 0.025 moles) was added and heating was continued for an additional 0.5 hour. The solution was cooled to room temperature, and to the cooled solution was cautiously added, with good agitation, a solution of sodium acetate (12.3 g, 0.15 moles) in water (50 ml) and the mixture was then boiled under reflux for 1 hour. The organic phase was separated, washed with water, dried, and evaporated. The residue was subjected to column chromatography on silica gel using ethyl acetate-hexane (1:9) as the eluding solvent. A yellow colored solid 2-(methylthio)-5-(4-fluorobenzoyl)pyrrole (3.2 g, 54%) was obtained which after crystallization from ether-hexane had m.p. 112-113 C. UV: (MeOH) 218.5, 248, 343 nm(epsilon9770, 8510, 13,800). IR: (CHCl3) 3440, 3250, 1610 cm-1. |
54% | With sodium acetate; trichlorophosphate; In water; 1,2-dichloro-ethane; | EXAMPLE 10 Preparation of 2-(methylthio)-5-(4-fluorobenzoyl)pyrrole (Step 2) A solution of <strong>[24167-56-4]N,N-dimethyl-4-fluorobenzamide</strong> (8.4 g, 0.05 moles) in anhydrous 1,2-dichloroethane (170 ml) containing phosphorus oxychloride (7.7 g, 0.05 moles) was heated at reflux temperature for 1 hour. At the end of this time 2-methylthiopyrrole (2.82 g, 0.025 moles) was added and heating was continued for an additional 0.5 hour. The solution was cooled to room temperature, and to the cooled solution was cautiously added, with good agitation, a solution of sodium acetate (12.3 g, 0.15 moles) in water (50 ml) and the mixture was then boiled under reflux for 1 hour. The organic phase was separated, washed with water, dried, and evaporated. The residue was subjected to column chromatography on silica gel suing ethyl acetate-hexane (1:9) as the eluding solvent. A yellow colored solid 2-(methylthio)-5-(4-fluorobenzoyl)pyrrole (3.2 g, 54%) was obtained which after crystallization from ether-hexane had m.p. 112-113 C. UV: (MeOH) 218.5, 248, 343 nm (epsilon 9770, 8510, 13,800). IR: (CHCl3) 3440, 3250, 1610 cm-1. NMR: (CDCl3) 2.48 (s, 3H); 6.25 (q, 1H; J=2.5, 4 Hz); 6.80 (q, 1H; J=2.5, 4 Hz); 7.12 (q, 2H; J=8, 8); 7.92 (q, 2H; J=5.5, 8); 10.67 (s, 1H, WH=22). Calcd. for C12 H10 FNOS: C, 61.24; H, 4.28. Found: C, 61.01; H, 4.21. |
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