Structure of 945381-62-4
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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. : | 945381-62-4 |
Formula : | C8H7FN2O |
M.W : | 166.15 |
SMILES Code : | O=C1NC2=C(C=C(F)C=C2N)C1 |
MDL No. : | MFCD13193359 |
InChI Key : | DIFFVSPISVQLKF-UHFFFAOYSA-N |
Pubchem ID : | 59250054 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 46.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.76 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.52 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.36 |
Solubility | 7.26 mg/ml ; 0.0437 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.91 |
Solubility | 20.6 mg/ml ; 0.124 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.8 |
Solubility | 0.263 mg/ml ; 0.00158 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 |
-7.18 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) |
1.7 |
* 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 |
---|---|---|
96% | With triethylamine; In tetrahydrofuran; at 0℃;Reflux; | A stirred solution of <strong>[945381-62-4]7-amino-5-fluoro-1,3-dihydro-indol-2-one</strong> (1.0 g, 6 mmol) obtained from Example 4 in 30 ml of tetrahydrofuran was added with triethylamine (1.3 ml, 9 mmol). The solution was cooled down to 0 C. in an ice-water bath and added with acetyl chloride (1.3 ml, 9 mmol) dropwise. The resulting mixture was heated to reflux for 1.5 hours and cooled until precipitate was formed. The solid was filtered, washed with water (50 ml×3) and dried in vacuo to give N-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-7-yl)-acetamide (1.2 g, 96%) as a white solid. |
96% | With triethylamine; In tetrahydrofuran; at 0℃; for 1.5h;Heating / reflux; | A stirred solution of 7-amino-5-fluoro-l,3-dihydro-indol-2-one (1.0 g, 6 mmol) obtained from Example 4 in 30 ml of tetrahydrofuran was added with tirethylamine (1.3 ml, 9 mmol). The solution was cooled down to 0C in an ice-water bath and added with acetyl chloride (1.3 ml, 9 mmol) dropwise. The resulting mixture was heated to reflux for 1.5 hours and cooled until precipitate was formed. The solid was filtered, washed with water (50 ml><3) and dried in vacuo to give N-(5-fluoro-2-oxo-2,3-dihydro-lH-indol-7-yl)-acetamide (1.2 g, 96%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.5% | With sulfuric acid; nitric acid; at -5 - 20℃; | 5-Fluoro-1,3-dihydro-indol-2-one (5.0 g, 33 mmol) was added with 98% sulfuric acid (17.6 ml) and 65%-68% nitric acid (2.1 ml) in an ice-water bath with salt at -5 C. Upon the completion of the addition, the mixture was stirred for 1 hour at room temperature and added with ice-water until precipitate was formed. The solid was filtered and washed with water (50 ml×3) and recrystallized from acetic acid and water to give 7-amino-5-fluoro-1,3-dihydro-indol-2-one (4.0 g, 62.5%) as an orange solid.MS m/z (ESI): 196 [M+1] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.4% | A solution of acetic anhydride (0.8 ml) and formic acid (0.6 ml) was stirred for 1 hour at room temperature, and added with <strong>[945381-62-4]7-amino-5-fluoro-1,3-dihydro-indol-2-one</strong> (2.0 g, 12 mmol) obtained from Example 4 in 30 ml of tetrahydrofuran and piperidine (0.02 ml). The resulting mixture was stirred for 3 hours at room temperature until a precipitate was formed. The solid was filtered and recrystallized from methanol to give N-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-7-yl)-formamide (700 mg, 30.4%) as a white solid.MS m/z (ESI): 195 [M+1] | |
30.4% | A mixture of acetic anhydride (0.8 ml) and formic acid (0.6 ml) was stirred for 1 hour at room temperature, and added with <strong>[945381-62-4]7-amino-5-fluoro-1,3-dihydro-indol-2-one</strong> 20b (2.0 g, 12 mmol) in 30 ml of tetrahydrofuran to the above mixture, followed by piperidine (0.02 ml). The resulting mixture was stirred for 3 hours until precipitates were formed, filtered to provide the crude product (1.95 g), and recrystallized from methanol to obtain the title compound 5-fluoro-7-formamido- indol-2-one 20c (700 mg, yield 30.4%) as a white solid. MS m/z (ESI): 195.1[M+1] | |
30.4% | A solution of acetic anhydride (0.8 ml) and formic acid (0.6 ml) was stirred for 1 hour at room temperature, and added with 7-amino-5-fluoro-l,3-dihydro-indol-2-one (2.0 g, 12 mmol) obtained from Example 4 in 30 ml of tetrahydrofuran and piperidine (0.02 ml). The resulting mixture was stirred for 3 hours at room temperature until a precipitate was formed. The solid was filtered and recrystallized from methanol to give N-(5-fluoro-2-oxo-2,3-dihydro-lH-indol-7-yl)-formamide (700 mg, 30.4%) as a white solid. MS m/z (ESI): 195[M+1] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.5% | With hydrogen;5% Pd(II)/C(eggshell); In acetic acid; at 20℃; | Step 2 7-Amino-5-fluoro-1,3-dihydro-indol-2-one 5-Fluoro-7-nitro-1,3-dihydro-indol-2-one 20a (4.0 g, 20 mmol) was dissolved in 200 ml of acetic acid under stirring, and added with palladium on activated carbon (1.0 g, 5%) at room temperature. The reaction system was stirred under a hydrogen atmosphere. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was filtered, and concentrated under reduced pressure to obtain the title compound 7-amino-5-fluoro-1,3-dihydro-indol-2-one 20b (3.2 g, yield 97.5%) as a white solid. |
97.5% | With hydrogen;5% Pd(II)/C(eggshell); In acetic acid; at 20℃; | 5-Fluoro-7-nitro-1,3-dihydro-indol-2-one 20a (4.0 g, 20 mmol) was dissolved in 200 ml of acetic acid under stirring, and added with palladium on activated carbon (1.0 g, 5%) at room temperature. The reaction system was stirred under a hydrogen atmosphere. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was filtered, and concentrated under reduced pressure to obtain the title compound 7-amino-5-fluoro-1,3-dihydro-indol-2-one 20b (3.2 g, yield 97.5%) as a white solid. MS m/z (ESI): 167.4[M+1] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.4% | Step 3 5-Fluoro-7-formamido-indol-2-one A mixture of acetic anhydride (0.8 ml) and formic acid (0.6 ml) was stirred for 1 hour at room temperature, and added with <strong>[945381-62-4]7-amino-5-fluoro-1,3-dihydro-indol-2-one</strong> 20b (2.0 g, 12 mmol) in 30 ml of tetrahydrofuran to the above mixture, followed by piperidine (0.02 ml). The resulting mixture was stirred for 3 hours until precipitates were formed, filtered to provide the crude product (1.95 g), and recrystallized from methanol to obtain the title compound 5-fluoro-7-formamido-indol-2-one 20c (700 mg, yield 30.4%) as a white solid. |
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