Structure of 31374-18-2
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CAS No. : | 31374-18-2 |
Formula : | C8H5ClN2O |
M.W : | 180.59 |
SMILES Code : | C1=C(Cl)C=CC2=C1NC=NC2=O |
MDL No. : | MFCD00115130 |
InChI Key : | PMLONMIODRHERC-UHFFFAOYSA-N |
Pubchem ID : | 135416175 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.37 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.58 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.71 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.629 mg/ml ; 0.00348 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.96 |
Solubility | 1.96 mg/ml ; 0.0108 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.85 |
Solubility | 0.0255 mg/ml ; 0.000141 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 |
-6.41 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) |
1.52 |
* 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 |
---|---|---|
72% | With sulfuric acid; nitric acid; at 0 - 90℃; for 3h; | To a 100-mL flask was added concentrated sulfuric acid (10 mL),concentrated nitric acid (5 mL) and 6b (10 g, 55.4 mmol) understirring at 0 C. The mixture was heated and stirred at 90 C for 3 h.After cooling to rt, the mixture was poured onto ice-water, filtered,washed with water, dried. The crude product was recrystallizedfrom acetic acid to afford 7-chloro-6-nitroquinazolin-4(3H)-one(6c) as a light yellow solid (9 g, yield 72%). mp 315e316 C; 1H NMR(DMSO-d6, ppm): d 12.79 (b, 1H), 8.67 (s, 1H), 8.31 (s, 1H), 8.01 (s,1H). |
71.2% | With sulfuric acid; nitric acid; at 90℃; for 3h;Cooling with ice; | 200 mL of concentrated sulfuric acid was placed in a 500 mL single-mouth round bottom flask under ice bath, and stirred.Slowly add 20 mL of concentrated nitric acid to concentrated sulfuric acid.After stirring for 30 min, it was slowly added dropwise to Intermediate 4 (50 g, 0.28 mol, 1 eq) using a constant pressure dropping funnel.The reaction solution was yellowish brown, most of the raw materials were insoluble, and the temperature was slowly raised to 90 C, and the reaction was carried out for 3 hours, and the reaction was completely confirmed by TLC. After cooling to room temperature, the reaction solution was poured into 3 L of ice water, stirred for 30 min, suction filtered, and the filter cake was washed with water.Drying, recrystallization from glacial acetic acid gave 44.5 g of a yellow solid.Yield 71.2%, |
68.3% | With sulfuric acid; nitric acid; at 20 - 45℃; | Under ice-water bath cooling,A solution of 7-chloro-3H-quinazolin-4-one (9.00 g, 50.0 mmol)(Concentrated sulfuric acid 30mL and fuming nitric acid 30mL), plus complete, stirring at room temperature lh,Heat to 45 C and stir overnight. The reaction solution was then poured into 60 mL of ice water, filtered and the resulting solid was filtered and washed with water, recrystallized from acetic acid, dried,To give 7.78 g of 7-chloro-6-nitro-3H-quinazolin-4-one as a yellow solid in 68.3% yield. |
62.7% | With sulfuric acid; nitric acid; In water; at 0 - 45℃; | Compound 0302 (18.0 g, 100 mmol) was added portionwise to a stirred mixture of concentrated sulfuric acid (60 mL) and fuming nitric acid (60 mL) which had been cooled to 0 0C, the mixture was stirred at ambient temperature for 1 hour and then heated to 45 0C overnight. The mixture was poured into the mixture of ice and water. The precipitate was isolated, washed with water and dried. Recrystallization from acetic acid to give the title compound 0303 (14.1 g, 62.7%). 1H NMR (DMSO-J6): delta 8.00 (s, IH), 8.27 (s, IH), 8.65 (s, IH), 12.70 (s, IH). |
62.7% | With sulfuric acid; nitric acid; at 0 - 45℃; | Step 22b. 7-Chloro-6-nitroquinazolin-4(3H)-one (compound 0303) Compound 0302 (18.0 g, 100 mmol) was added portionwise to a stirred mixture of concentrated sulfuric acid (60 mL) and fuming nitric acid (60 mL) which had been cooled to 0 C., the mixture was stirred at ambient temperature for 1 hour and then heated to 45 C. overnight. The mixture was poured into the mixture of ice and water. The precipitate was isolated, washed with water and dried. Recrystallization from acetic acid to give the title compound 0303 (14.1 g, 62.7%). 1H NMR (DMSO-d6): delta 8.00 (s, 1H), 8.27 (s, 1H), 8.65 (s, 1H), 12.70 (s, 1H). |
62.7% | With sulfuric acid; nitric acid; at 0 - 45℃; | Step 22b. 7-Chloro-6-nitroquinazolin-4(3H)-one (compound 0303); Compound 0302 (18.0 g, 100 mmol) was added portionwise to a stirred mixture of concentrated sulfuric acid (60 mL) and fuming nitric acid (60 mL) which had been cooled to 0 C., the mixture was stirred at ambient temperature for 1 hour and then heated to 45 C. overnight. The mixture was poured into the mixture of ice and water. The precipitate was isolated, washed with water and dried. Recrystallization from acetic acid to give the title compound 0303 (14.1 g, 62.7%). 1H NMR (DMSO-d6): delta 8.00 (s, 1H), 8.27 (s, 1H), 8.65 (s, 1H), 12.70 (s, 1H). |
With sulfuric acid; nitric acid; | Reference example 3: 7-chloro-6-nitro-4(3H)-quinazolone 7-Chloro-4(3H)-quinazolone (20.9 g, 0.116 mmol) obtained in Reference example 2 was dissolved in a mixed solution of concentrated sulfuric acid (45 ml) and fuming nitric acid (45 ml) and stirred at 80 C for 2 hours. After completion of the reaction, the reaction solution was cooled to room temperature and poured into ice water (900 ml). The precipitated solid was filtered off, and the filtered crude crystal was suspended in acetic acid (440 ml) and stirred at 80 C for 1 hour. | |
With sulfuric acid; nitric acid; at 0 - 90℃; for 3h; | 10g of the above 7-chloro-quinazolone was added into a mixed acid of concentrated sulphuric acid and fuming nitric acid (40ml) slowly in an ice-bath. Then the mixture was heated to 90 and reacted at this temperature for 3h. The clear solution formed was then poured into 300mL of ice-water carefully, and yellow solid was deposited, which was filtered, washed with water and redissolved into hot acetic acid, to deposit the crystalline of 6-nitro-7-chloro-quinazolone, which was collected and 6.50g of the product was achieved. | |
With sulfuric acid; nitric acid; at 0 - 90℃; for 3h; | 10 g of the above 7-chloro-quinazolone was added into a mixed acid of concentrated sulphuric acid and fuming nitric acid (40 ml) slowly in an ice-bath. Then the mixture was heated to 90 C. and reacted at this temperature for 3 h. The clear solution formed was then poured into 300 mL of ice-water carefully, and yellow solid was deposited, which was filtered, washed with water and redissolved into hot acetic acid, to deposit the crystalline of 6-nitro-7-chloro-quinazolone, which was collected and 6.50 g of the product was achieved. | |
With sulfuric acid; nitric acid; at 90℃; for 1h;Cooling with ice; | The compound BB2 under 10g ice bath was slowly added concentrated sulfuric acid and fuming nitric acid (20ml: 20ml) mixed acid, the addition is complete warm to 90 C, for about 1 hour. The reaction solution was poured into 300ml of ice water, the precipitated solid was collected by filtration and the solid was the crude compound 12g BB3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1-methyl-pyrrolidin-2-one; | EXAMPLE 2 7-Chloro-3H-quinazolin-4-one To a solution of <strong>[5900-59-4]2-amino-4-chlorobenzamide</strong> (58 g, 0.34 mol) in hot (60° C.) N-methylpyrrolidone (170 mL), triethylorthoformate (151 g, 1.02 mol, 3 equiv) and a 1,4-dioxane 5N HCl solution (ca. 15 mL) were added. The resulting solution was heated at 110° C. for 18 h. Then, the mixture was cooled to room temperature, was poured over cold water and was brought to pH 7 with saturated NaHCO3 solution. The formed precipitate was filtered, washed with water and dried to give the desired product as a slightly beige solid (58 g, 94percent). mp 253-256° C.; 1H NMR (300 MHz, MeOH-d4) delta (MeOH) 8.19 (d, J=8.6 Hz, 1H, arom), 8.10 (s, 1H, N=CH-N), 7.70 (d, J=2, 1H, arom), 7.54 (dd, J=2, J=8.6, 1H, arom). Analysis calculated for C8H5ClN2O: C 53.21; H 2.79; N 15.51. Found: C 53.46; H 2.77; N 15.48. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With hydrogenchloride; In water; trimethyl orthoformate; | Reference example 2: 7-chloro-4(3H)-quinazolone 2-Amino-4-chlorobenzamide (25.6 g, 0.150 mol) obtained in Reference example 1 was dissolved in trimethyl orthoformate (560 ml), and to this added was concentrated hydrochloric acid (15 ml), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was filtered, and the crude crystal filtered was suspended in water (250 ml) and neutralized with 3N NaOH aqueous solution. The neutralized solution was filtered, the solid being washed with water on the funnel to give 20.9 g (yield 77percent) of the title compound as white crystal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With [Cp*Ir(2,2'-bpyO)(H2O)]; caesium carbonate; at 130℃; for 2h;Inert atmosphere; Microwave irradiation; | 2-Amino-4-chlorobenzamide (85 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO)(5.4 mg, 0.005 mmol, 1 molpercent),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.The tube was nitrogen protected and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ° C for 2 hours, it was cooled to room temperature. Rotary evaporation to remove the solvent,Pure target compound was then obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 70percent |
Tags: 31374-18-2 synthesis path| 31374-18-2 SDS| 31374-18-2 COA| 31374-18-2 purity| 31374-18-2 application| 31374-18-2 NMR| 31374-18-2 COA| 31374-18-2 structure
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H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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