Structure of 222036-66-0
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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. : | 222036-66-0 |
Formula : | C8H8N2O |
M.W : | 148.16 |
SMILES Code : | NC2=CC=C1C(NCC1=C2)=O |
MDL No. : | MFCD10000828 |
InChI Key : | RGJCJWXNNDARPQ-UHFFFAOYSA-N |
Pubchem ID : | 21956239 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 45.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.22 |
Solubility | 8.95 mg/ml ; 0.0604 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.8 |
Solubility | 23.4 mg/ml ; 0.158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.459 mg/ml ; 0.0031 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 |
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 |
-7.14 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) |
1.08 |
* 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 |
---|---|---|
84% | With hydrogenchloride; iron; In ethanol; water; for 2h;Heating; | A mixture of 5-nitro-1 lead noise isobutyl ketone Jie (100mg, 0.56mmoL), reduced iron powder (314mg, 5.6mmoL) was added to ethanol (2. OmL) and concentrated hydrochloric acid (0.5mL) and heated under reflux for 2 hours , TLC the reaction was complete. Cooling, the methanol solution saturated with ammonia (NH3) neutralizing the acid, diatomaceous earth filtration, washed with methanol, the solvent evaporated under reduced pressure to give a white solid 70.0mg, 84% yield |
76.2% | With hydrogen;palladium 10% on activated carbon; In methanol; for 1h; | Step C / Intermediate B8: 5-aminoisoindoiin-1 -oneTo a solution of 5-nitroisoindolin-1 -one (60 mg, 0.337 mmoi) in methanol (20 mL) was added palladium on carbon (10 %, 50 mg). The mixture was stirred under an atmosphere of hydrogen for 1 hour. Filtration through Celite, followed by concentration led to 5-aminoisoindoiin-1 -one as a tan solid (38 mg, yield 78.2 %). |
48% | With iron; ammonium chloride; In ethanol; water; at 80℃; for 2h; | Step 4: Synthesis of 5-Amino-2,3-dihydro-isoindol-1-one To a suspension of Fe (1.1 g, 19.6 mmole), NH4Cl (1.5 g, 28 mmole) in a mixture of ethanol/water (30 ml/7 ml) at 80 C. was added a mixture of 5-Nitro-2,3-dihydro-isoindol-1-one (1 g, 5.6 mmole) in 10 ml ethanol. The reaction mixture was stirred at 80 C. for 2 hours. Mixture was cooled down, filtered off, solid was washed with 50 ml ethanol. The filtrate was concentrated, taken into 50 ml ethylacetate, washed with 20 ml water. Organic layer was dried over Na2SO4, filtered and concentrated to give about 900 mg crude. Trituration with methyl t-butylether gave 400 mg pure product, 48% yield. A 18 ml vial was loaded with a mixture of 30% H2O2 (1 ml), 3N NaOH (3 ml) and MeOH (2.5 ml). To this mixture 5-Amino-pyridine-2-carbonitrile (450 mg, 3.78 mmole) was added at room temperature. Reaction mixture was stirred at rt for 45 minutes, TLC showed the starting material to be consumed. The mixture was diluted with water and filtered; the solid was washed with water and dried to give 480 mg product, 92% yield. |
With hydrogenchloride; ethanol; water; iron; at 95℃; for 2h; | 5-Amino-2,3-dihydroisoindol-l-oneH2N; [693] Iron powder (158mg, 2.83mmol), water (61uL), and HC1 (37%, 5uL,0.566mmol) were added into the suspension of 5-nitro-2,3-dihydroisoindol-l-one (50.4mg,0.283mmol) in EtOH (754|^L). The above mixture was heated at 95C for 2h. After thattime, several drops of 7N NH3 in MeOH were added to basify the solution, and the solid wasfiltered off. The filtrate was concentrated in vacua to obtain a light-yellow solid that waspurified by preparative TLC eluting with 10% MeOH/CH2Cl2 to give a light-yellow solid of5-amino-2,3-dihydroisoindol-l-one. 'HNMR (CD3OD, 400 MHz): 5 = 7.48 (s, 1 H), 8.08 (s,2 H), 9.91 (s, 1 H), 10.66 (d, 1 H, J= 8.8 Hz). MS (ES+): m/z 149.21 (100) [MH1"]. HPLC: *R= 1.20 min (ZQ2000, polar_5 min). | |
With hydrogen;palladium on activated charcoal; In methanol; for 1h;Inert atmosphere; | To a solution of <strong>[110568-64-4]5-nitro-2,3-dihydro-1H-isoindol-1-one</strong> (60 mg, 0.337 mmol) in methanol (20 mL) was added 50 mg of 10% Pd on carbon. The mixture was hydrogenated (with a balloon) for 1 hour. Filtration through Celite followed by concentration led to 38 mg of 5-amino-2,3-dihydro-1H-isoindol-1-one as a tan solid. | |
Step 3: 5-aminoisoindolin-1-oneIron powder (2.51 g, 45 mmol), water (0.97 ml) and HCl (37%, 0.74 ml), were added to a stirred suspension of the <strong>[110568-64-4]5-nitroisoindolin-1-one</strong> (800 mg, 4.5 mmol) from step 2 of this example in EtOH (11.2 ml). The mixture was heated at 95 C for 2h. Ammonia (7N in MeOH) was added (ImL) to make the pH of the mixture alkaline. The mixture was filtered to removed undissolved solids and the filter cake washed with EtOH (2x40 ml). The filtrate and organic washes were combined and concentrated in vacuum to give the titled compound. | ||
With palladium on activated charcoal; hydrogen; In methanol; at 50℃; under 2585.81 Torr; for 2h; | Toa solution of7D (35 g, 0.2 mol) in MeOH(350 mL) was added Pd/C (7 g), the mixture was stirred at 50C underH2 at 50 psi for 2 hr.Themixturewas filtered and concentratedin vacuumto afford crude7E (30g) as a white solid. |
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