Structure of 226260-01-1
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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. : | 226260-01-1 |
Formula : | C9H10FNO2 |
M.W : | 183.18 |
SMILES Code : | O=C(N(OC)C)C1=CC=CC(F)=C1 |
MDL No. : | MFCD02684305 |
InChI Key : | RQOXEMMAAVCMRU-UHFFFAOYSA-N |
Pubchem ID : | 21265757 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.38 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.54 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.25 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.88 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.08 |
Solubility | 1.51 mg/ml ; 0.00826 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.76 |
Solubility | 3.19 mg/ml ; 0.0174 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.48 |
Solubility | 0.611 mg/ml ; 0.00333 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 |
-6.33 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 |
1.0 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) |
1.6 |
* 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 |
---|---|---|
86.5% | With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere | To a solution of Ν,Ο-dimethylhydroxylamine hydrochloride (138 g, 1.42 mol) in DCM (1.5 L) was added Et3N (383 g, 3.78 mol) at room temperature (RT). To the stirred mixture, 1-1 (150 g, 946 mmol) was added dropwise at 0 °C under N2 atmosphere. The solution was stirred at the same temperature for 1 h, and then slowly warmed to RT for 10 h. The mixture was added to water (~1L) and extracted with EtOAc (2 x 500 mL). The combined organic phases were dried with Na2S04, filtered and concentrated. The residue was purified by flash column chromatography (eluent: PE) to give 1-2 as a white solid (150 g, yield: 86.5percent). 1H NMR (400 MHz, CDC13): δ 7.49-7.43 (1 H, m), 7.41-7.32 (2 H, m), 7.18- 7.10 (1 H, m), 3.54 (3 H, s), 3.34 (3 H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 75 h; | EXAMPLE 4 3-Fluoro-N-methoxy-N-methylbenzamide To a suspension of 3-fluorobenzoic acid (140 mg, 1 mmol) and N dimethylhydroxylamine hydrochloride (107 mg, 1.1 mmol) in dichloromethane (2.5 mL) was added 1- [3- (dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (EDC) (211 mg, 1.1 mmol) and the mixture stirred at room temperature for 75 h. The solvents were removed under reduced pressure and the residue chromatographed using ethyl acetate- hexane (4: 6) to separate the pure product (130 mg, 71percent). H-n. m. r. (CDC13) 8 3.36 (s, 3H, N-Me), 3.55 (s, 3H, N-OMe), 7. 1. -7.2 (m, 1H, ArH), 7.3-7. 5 (m, 3H, Ar) |
71% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 25℃; for 75 h; | Example 4 3-Fluoro-N-methoxy-N-methylbenzamide To a suspension of 3-fluorobenzoic acid (140 mg, 1 mmol) and AC (7 dimethylhydroxylamine hydrochloride (107 mg, 1.1 mmol) in dichloromethane (2.5 mL) was added 1- [3- (DIMETHYLAMINO) PROPYL]-3-ETHYLCARBODIIMIDE hydrochloride (EDC) (211 mg, 1.1 mmol) and the mixture stirred at room temperature for 75 h. The solvents were removed under reduced pressure and the residue chromatographed using ethyl acetate- hexane (4: 6) to separate the pure product (130 mg, 71percent). APOS;H-N. m. r. (CDCL3) 8 3.36 (s, 3H, N-Me), 3.55 (s, 3H, N-OMe), 7.1.-7. 2 (m, 1H, Ar), 7.3-7. 5 (m, 3H, Ar) |
61% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 3 h; Inert atmosphere | 3-fluoro-N-methoxy-N-methylbenzamide To a solution of 3-fluorobenzoic acid (30 g, 214.1 mmol) in DCM (300 mL) were added EDC.HCl (45 g, 235 mmol) and N,O-dimethylhydroxylamine.HCl (23 g, 235 mmol) at 0° C. under N2. The reaction mixture was stirred at rt for 3 h, then diluted with water (1000 mL) and extracted with DCM (3*200 mL). The organics were washed with brine, dried over Na2SO4, and concentrated to obtain the 3-fluoro-N-methoxy-N-methylbenzamide (24 g, 61percent). (183.91 [M+H]) 1H NMR: (400 MHz, CDCl3) δ: 3.38 (s, 3H), 3.57 (s, 3H), 7.14-7.19 (m, 1H), 7.37-7.43 (m, 2H), 7.48-7.50 (d, J=7.6, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.5% | With triethylamine In dichloromethane at 0 - 20℃; for 11 h; Inert atmosphere | 10264] To a solution of N,O-dimethylhydroxylamine hydrochloride (138 g, 1.42 mol) in DCM (1.5 L) was addedEt3N (383 g, 3.78 mol) at RT. To the stirred mixture, G-1 (150 g, 946 mmol) was added dropwise at 00 C. under N2 atmosphere. The solution was stirred at the same temperature for 1h, and then slowly warmed to RT for 10 h. The mixture wasadded to water (.—1 L) and extracted with EtOAc (2x500 mE).The combined organic phases were dried with Na2504, filtered and concentrated. The residue was purified by flashcolunm chromatography (eluent: PE) to give G-2 as a white solid (150 g, yield: 86.5percent). ‘H NMR (400 MHz, CDC13): ö 7.49-7.43 (1H, m), 7.41-7.32 (2H, m), 7.18-7.10 (1H, m),3.54 (3H, s), 3.34 (3H, s). |
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