Structure of 39549-79-6
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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. : | 39549-79-6 |
Formula : | C8H10N2O |
M.W : | 150.18 |
SMILES Code : | O=C(N)C1=CC=C(C)C=C1N |
MDL No. : | MFCD00221474 |
Boiling Point : | No data available |
InChI Key : | RUHKZVAPXHIWJH-UHFFFAOYSA-N |
Pubchem ID : | 2801474 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H317-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 43.91 |
TPSA ? Topological Polar Surface Area: Calculated from |
69.11 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.85 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.56 |
Solubility | 4.17 mg/ml ; 0.0278 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.74 |
Solubility | 2.74 mg/ml ; 0.0182 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.0 |
Solubility | 1.51 mg/ml ; 0.0101 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 |
-6.71 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) |
1.0 |
* 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 |
---|---|---|
91% | at 100℃; for 6h; | 2-amino-4-mthylbenzamide (4.93 g, 32.8 mmol) obtained in above was added with formic acid (30 mL, 787.9 mmol), followed by stirring for 6 hours at 100°C. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and washed with water. The filtered solid was dried with warm wind in an oven (40°C) for 6 hours or more to obtain the title compound (4.79 g, 91percent). 1H-NMR Spectrum (300 MHz, DMSO-rftf): delta 8.06 (s, 1H), 8.00 (d, 1H), 7.47 (s, 1H), 7.34 (d, 1H), 2.45 (s, 3H) MS(ESI+, m/z): 161 [M+H]+ |
91% | at 100℃; for 6h; | <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (4.93 g, 32.8 mmol) obtained in <Step 1> above was added with formic acid (30 mL, 787.9 mmol), followed by stirring for 6 hours at 100° C. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and washed with water. The filtered solid was dried with warm wind in an oven (40° C.) for 6 hours or more to obtain the title compound (4.79 g, 91percent). 1H-NMR Spectrum (300 MHz, DMSO-d6): delta 8.06 (s, 1H), 8.00 (d, 1H), 7.47 (s, 1H), 7.34 (d, 1H), 2.45 (s, 3H) MS (ESI+, m/z): 161 [M+H]+ |
84% | at 100℃; for 6h; | A mixture of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (20 g, 133 mmol) and formic acid (120 ml, 3129 mmol) was heated to 100 0C for 6 h. The reaction was cooled to RT and the volatiles were removed under reduced pressure. The residue was then washed carefully with aqueous saturated sodium bicarbonate and then with water. The tan solid was then dried in a vacuum oven at 45 0C overnight to give 7-methylquinazolin-4(3H)-one (18.00 g, 84percent yield). MS (ESI, pos. ion) m/z: 161 [M+H]+ |
Example 332; Preparation of 7-methyIquinazolin-4(3H)-oneA mixture of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (20 g, 133 mmol)and formic acid (120 ml, 3129 mmol) was heated to 100 0C. After 6 hours, the reaction was cooled down to to RT and the volatiles were removed under reduced pressure. The residue was then washed carefully with aqueous saturated sodium bicarbonate and then with water. The tan solid <n="118"/>was then dried in a vacuum oven at 45 0C overnight to give 7-methylquinazolin-4(3H)- one. MS (M+H)+ 161. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | A suspension of 2-amino-5-methylbenzamide (404 mg, 2.7 mmol) in HCl (2N, 5 mL) at 0 C was treated with NaNO2 (208 mg, 3.0 mmol). The mixture was stirred for 1 h, then made basic with Na2CO3 (20 % soln). The resulting solid was collected via vacuum filtration to provide 249 mg (57 %) of the title compound as a brown solid. 1H EPO <DP n="53"/>NMR (DMSO-J6) delta 8.11 (d, 1 H), 7.96 - 8.00 (m, 1 H), 7.73 (ddd, 1 H), 2.56 (s, 3 H). MS (ES) 160 (M - H), 162 (M + H). | |
General procedure: A solution of anthranilamide (30 mmol) in 1N HCl (120 mL) was stirred at 0 C for 20 min. Then, sodium nitrite (60 mmol) dissolved in deionized water (100 mL) was added dropwise to the above solution for 40 min. After another 2 h of stirringat 0 C, 30% NaOH solution was added slowly to adjustp H value to 8.0. The reaction mixture was allowed to stir vigorously for 15 min. The precipitated product was filtered, washed with deionized water (200 mL), and dried to afford compounds 10 in yields of 40-92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sulfuric acid; In water; at 120℃; for 0.333333h; | Concentrated sulfuric acid (3 mL) was carefully added to a suspension of 2- amino-4-methylbenzonitrile (800 mg, 6.1 mmol) in H2O (1 mL). The solution was then placed into an oil bath, pre-heated to 120 0C, the reaction stirred for 20 min and then immediately cooled in an ice bath. The solution was made basic via the addition of 5 percent NaOH and the resulting solid collected via vacuum filtration. 484.4 mg (53 percent) of the title compound as a light brown solid were obtained. 1H NMR (DMSO-dbeta) delta 7.63 (br s, 1 H), 7.42 (d, 1 H), 6.95 (br s, 1 H), 6.55 (br s, 2 H), 6.45 - 6.48 (m, 1 H), 6.29 (ddd, 1 H), 2.16 (s, 3 H). MS (ES) 134 (M - 16). |
43% | With potassium hydroxide; In ethanol; for 8h;Reflux; | 2-amino-4-methylbenzonitrile (10 g, 75.7 mmol) was dissolved in ethanol, added with potassium hydroxide (21.2 g, 378 mmol), followed by refluxing for 8 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and dissolved in ethyl acetate. The organic layer formed was washed with a saturated aqueous solution of sodium bicarbonate and brine. The obtained organic layer is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized from ethanol to obtain the title compound (4.9 g, 43percent). 1H-NMR Spectrum (300 MHz, DMSO- 6): delta 7.40 (d, 1H), 6.52 (s, 2H), 6.45 (s, 1H), 6.28 (d, lH), 2.14 (s, 3H) |
43% | With potassium hydroxide; In ethanol; for 8h;Reflux; | 2-amino-4-methylbenzonitrile (10 g, 75.7 mmol) was dissolved in ethanol, added with potassium hydroxide (21.2 g, 378 mmol), followed by refluxing for 8 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and dissolved in ethyl acetate. The organic layer formed was washed with a saturated aqueous solution of sodium bicarbonate and brine. The obtained organic layer is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized from ethanol to obtain the title compound (4.9 g, 43percent). 1H-NMR Spectrum (300 MHz, DMSO-d6): delta 7.40 (d, 1H), 6.52 (s, 2H), 6.45 (s, 1H), 6.28 (d, 1H), 2.14 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.2 g | With iron; ammonium chloride; In ethanol; water; for 2h;Reflux; | General procedure: To a solution of 5-nitro-N-(3-(trifluoromethyl)phenyl)isoquinolin-1-amine (1.0 g, 3.0 mmol) in a mixture of EtOH:H2O (8:2, 10 mL) were added iron powder (1.26 g, 4.8 mmol), and NH4Cl (1.6 g, 30.0 mmol). The reaction mass was heated at reflux for 2 h and filtered. The filtrate was concentrated and the residue was purified by column chromatography to afford 0.800 g of the title product. 1H NMR (300 MHz, DMSO-d6): delta 9.18 (s, 1H), 8.35 (s, 1H), 8.20 (d, J=7.8 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.42-7.24 (m, 3H), 6.86 (d, J=7.5 Hz, 1H), 5.84 (s, 2H). The title compound was prepared following the procedure described in Step 3 of Intermediate-i using 4-methyl- 2-nitrobenzamide (1.60 g, 8.88 mmol), iron powder (2.97 g,53.33 mmol), and NH4C1 (2.85 g, 53.33 mmol) in EtOH (8 mE) and water (2 mE) to afford 1.2 g of the title product. 1HNMR (300 MHz, DMSO-d5): oe 7.62 (br s, 1H), 7.42 (d, J=7.8 Hz, 1H), 6.93 (br s, 1H), 6.53 (s, 2H), 6.46 (s, 1H), 6.29 (d, J=7.8 Hz, 1H), 2.15 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With hydrogenchloride; sodium methylate; In tetrahydrofuran; methanol; | Step A:To a solution of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (3 g, 20.0 mmol) in THF (40 mL) was added 5-(4-fluorophenyl)-1,3-dioxolane-2,4-dione from Example 16 (4.7 g, 24 mmol) and the solution was stirred for 2 hrs at 50° C. Sodium methoxide in MeOH (25percent, 5.2 mL, 24 mmol) was then added and the solution was stirred at 50° C. overnight.The reaction mixture solution was concentrated, 2N HCl was added and the mixture was filtered.The collected solid was dried to give 2-((4-fluorophenyl)(hydroxy)methyl)-7-methylquinazolin-4-ol (5.14 g, 91percent) which was used without further purification. LC-MS (ESI) m/z 285 (M+H)+. |
00319] Step A: To a solution of <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (3 g, 20.0 mmol) in THF (40 mL) was added 5-(4-fluorophenyl)-l,3-dioxolane-2,4-dione from Example 16 (4.7 g, 24 mmol) and the solution was stirred for 2 h at 50 0C. Sodium methoxide in MeOH (25percent, 5.2 mL, 24 mmol) was then added and the solution was stirred at 50 0C overnight. The reaction mixture solution was concentrated, 2N HCl was added and the mixture was filtered. The collected solid was dried to give 2-((4- fluorophenyl)(hydroxy)methyl)-7-methylquinazolin-4-ol (5.14 g, 91percent) which was used without further purification. LC-MS (ESI) m/z 285 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; In 1,2-dichloro-ethane; at 20℃; | 00325] Step B: To a solution of 2-(2,2-difluoro-2-(4-fluorophenyl)acetamido)-4- methylbenzamide (5.85 g, 0.0181 mol) in DCE (120 mL) were added TEA (91.5 mL, 0.724 mol) and chlorotrimethylsilane (34.4 mL, 0.272 mol) at rt. The reaction mixuture was stirred at 85 0C overnight. After cooling to rt, the solid was filtered and the filtrate was concentrated to dryness. The residue was taken in a mixture of EtOAc/THF (1: 1) and washed with water and brine. Pure product was obtained after crystallization from hot EtOAc (2.02 g, 37percent); LC-MS (ESI) m/z 305 (M+H)+. |