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CAS No. : | 18740-39-1 |
Formula : | C6H2Cl2N2S |
M.W : | 205.06 |
SMILES Code : | ClC1=NC2=C(C(=N1)Cl)C=CS2 |
MDL No. : | MFCD09743991 |
InChI Key : | HRXNGIQKOWQHCX-UHFFFAOYSA-N |
Pubchem ID : | 12217324 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.44 |
TPSA ? Topological Polar Surface Area: Calculated from | 54.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 3.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 3.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.85 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 3.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.9 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.91 |
Solubility | 0.0253 mg/ml ; 0.000123 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -4.3 |
Solubility | 0.0104 mg/ml ; 0.0000505 mol/l |
Class? Solubility class: Log S scale | Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.83 |
Solubility | 0.03 mg/ml ; 0.000146 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 | -5.08 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 | 0.0 |
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) | 2.37 |
* 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 |
---|---|---|
63% | With ammonium hydroxide; In ethanol; at 20℃; for 48h; | <strong>[18740-39-1]2,4-dichlorothieno[2,3-d]pyrimidine</strong> (51 g, 250 mmol),28percent aqueous ammonia (94g, 750mmol a flask containing 500mL of ethanol,The reaction was stirred for 48 hours with stirring at room temperature.TLC monitors the reaction endpoint.The precipitated solid was filtered, and the ethanol was rinsed.Drying gave Compound 22-1 (29 g, yield 63percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With trichlorophosphate; In N,N-dimethyl-formamide; at 115℃; for 8h; | Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (12) (2.5 g, 0.012 mol) and a drop of DMF were added to 20 mL POCl3. Heated to 115 C for 8 h. After cooling to room temperature, the reactant was added to 500 g ice-water mixture slowly. The product was filtered off and dissolved in CH2Cl2. The insoluble was filtered off and the filtrate was distilled under reduced pressure to afford 1.7g 2,4-dichlorothieno[2,3-d]pyrimidine (13). Yield: 56.0 %, 1H NMR (400 MHz, DMSO) delta 8.16 (d, J=3.4 Hz, 1H, Ar-H), 7.62 (d, J=3.4 Hz, 1H, Ar-H). ESI-MS m/z: 205.1. |
56% | With N,N-dimethyl-formamide; trichlorophosphate; at 115℃; for 5h; | To 1 g of dry thieno [2,3-d] pyrimidine-2,4 (1H, 3H) -dione was added 10 g of phosphorus oxychloride,Add 1 drop of DMF catalyst, heating to 115 , the reaction 5h, the reaction is completed, the reaction slowly added to the crushed ice,While stirring vigorously,A brown solid,Filter, filter residue dissolved in 50mL of dichloromethane, to the solution by adding 1g activated carbon and 2g silica gel,Heated to 45 reflux decolorization 1h, while the hot filter, remove the solvent,Pale yellow solid,2,4-dichlorothieno [2,3-d] pyrimidine in a yield of 56.0%. |
56% | With N,N-dimethyl-aniline; trichlorophosphate; In acetonitrile; at 0 - 85℃; for 24h; | Thieno[2,3-d] pyrimidine-2,4 (1H, 3H) -dione (IX-2) (5.0 g, 29.7 mmol)And 3 mL of N, N-dimethylaniline were dissolved in 30 mL of acetonitrile,It was cooled to 0 C.16 mL of phosphorus oxychloride is kept at the reaction temperature not higher than 25 C.I am dripping slowly. The reaction mixture was heated and stirred at 80-85 C. for 24 hours.The reaction solution was cooled to 15 C.,Was slowly added to 70 mL of ice water.The obtained slurry was collected by filtration,And washed with cold water (20 mL).After drying, column chromatography (elution solvent: hexane: dichloroMethane = 1: 2)3.41 g (yield 56%) of the dichloro compound (IIa-2) was obtained as gray crystals. |
49% | 3 g (0.018 mol) of the intermediate lib was placed in a 100 mL three-necked flask,30 mL (0.329 mol) of phosphorus oxychloride was slowly added dropwise,After 30 min addition, 2 drops of DMF were added to the reaction mixture and the reaction was heated to reflux for 8 h. The reaction was poured into 1000 g of ice water with stirring, and a large amount of orange-colored solid was precipitated. The filter cake was washed with a large amount of water and dried at 45 C for 24 hours to obtain 1.8 g of an orange solid in a yield of 49%. | |
41% | With trichlorophosphate; at 106℃; for 3h;Inert atmosphere; | Under a nitrogen streamThieno [2,3-d] pyrimidine-2,4 (1H, 3H) -dione (8.4 g, 50.0 mmol) and phosphoryl chlorideL), which was stirred for 3 hours at 106 C. After completion of the reaction, the organic layer was separated using ethyl acetateWater was removed using MgSO4. The solvent of the organic layer was removed, and the residue was purified by column chromatography to obtain the target compound2,4-dichlorothieno [2,3-d] pyrimidine (4.2 g, 20.5 mmol, yield 41%). |
40% | With trichlorophosphate; at 116℃; for 3h; | A mixture of thieno[2,3-phiyrimidine-2,4(l//,3//)-dione (100 mg, 0.59 mmol) and phosphonyl chloride (2 mL, 21.5 mmol) was heated at 1 16 0C for 3 h. Upon completion of the reaction, the reaction mixture was poured into ice and extract with ethyl acetate 3 times. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by column chromatography, eluting with Hexanes/Ethyl Acetate (9: 1) afforded the product as a white solid (48.1 mg, 40%): 1H NMR (DMSO, 300 MHz) delta 7.6 (d, J = 6.3 Hz, IH), 8.13(d, J = 5.7 Hz, IH). |
35.5% | With N,N-dimethyl-aniline; trichlorophosphate; for 16h;Reflux; | A total of 0.8 mL N,N-dimethylaniline was added to 3.0 g of thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione 6a in 20 mL POCl3. The mixture was then heated under reflux for 16 h. Excess POCl3 was removed in vacuo, and the resulting residue was treated with ice water to yield a precipitate. The solid was collected by filtration, washed with water and dried over a funnel to afford solid 7a (1.3 g, yield 35.5%). 1H NMR (400 MHz, CDCl3): delta 7.62 (d, J = 6.4 Hz, 1H), 7.43 (d, J = 6.4 Hz, 1H). |
With trichlorophosphate; at 200℃; for 2.3h; | EXAMPLE 402,4-Dichlorothieno[2,3-d]pyrimidine; The dione of Example 39 (2.6 g) was placed into a pressure vessel with phosphorus oxychloride (15 mL). The mixture was heated at 200 0C for 2.3 hours and then cooled to room temperature and concentrated under reduced pressure. Residual phosphorus oxychloride was azeotroped . twice with toluene (30 mL) under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The resulting layers were separated and the organic layer was filtered through anhydrous magnesium sulfate and concentrated to dryness under reduced pressure to give 1.06 g of the title compound: MS (ESI+) for C6H2N2CI2S m/z205.0 (M+H)+. 1H NMR (400 MHz, CDCI3) delta 7.42 (d,1 H), 7.61 (d,1 H). | |
With N,N-dimethyl-aniline; trichlorophosphate; In toluene; at 100℃; for 3h; | To a solution of 1H-thieno[2,3-d]pyrimidine-2,4-dione (62) (92.8 mg, 0.552 mmol) in toluene (1 mL) were added N,N-dimethylaniline (0.140 mL, 1.10 mmol) and phosphoryl chloride (0.280 mL, 3.00 mmol). The reaction mixture was warmed to 100 C and stirred for 3 h. After cooling to room temperature, H2O was added to the reaction mixture and the mixture was extracted with CHCl3. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give 2,4-dichlorothieno[2,3-d]pyrimidine (63). This compound was used for the next reaction without further purification.To a solution of 63 in DMF (4 mL) was added ethyl 2-(4-aminophenyl)acetate (95.2 mg, 0.531 mmol) and the reaction mixture was stirred at 65 C for 2.5 h. After cooling, H2O was added to the reaction mixture and the mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was chromatographed (EtOAc/hexane = 0% to 100%) to give the title compound (85.9 mg, 0.247 mmol, 45%) as a colorless solid. 1H NMR (CDCl 3) delta: 1.28 (3H, t, J = 7.4 Hz), 3.64 (2H, s), 4.18 (2H, q, J = 7.4 Hz), 7.03 (1H, d, J = 5.7 Hz), 7.21 (1H, s), 7.29 (1H, d, J = 5.7 Hz), 7.32 (2H, d, J = 8.6 Hz), 7.56 (2H, d, J = 8.6 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate; In N,N-dimethyl-aniline; for 3h; | General procedure: 2,4-Dihydroxythieno[3,2-d]pyrimidine (M1) (3.38 g, 0.020 mol) was added to the reaction flask.Phosphorus oxychloride (11.6 ml, 0.127 mol) was added.N,N-dimethylaniline (7.44 ml, 0.058 mol) was added dropwise with stirring at room temperature for 3 hours under reflux.Stop heating,Pour into 100ml of ice water.Precipitating a brownish black solid,Filtering,dry,Column chromatography (petroleum ether - ethyl acetate = 3: 1) to give a pale yellow solid 2.10g,The yield was 51.2percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; | EXAMPLE 41 4-[4-(1 ,1 '-biphenyl-4-ylcarbonyl) piperazin-1 -yl]-2-chlorothieno[2,3d]pyrimidine; To a mixture of <strong>[18740-39-1]2,4-dichlorothieno[2,3-d]pyrimidine</strong> (Example 40, 0.4 g) in THF/DMF (20/8 mL) was added diisopropylethylamine (0.44mL) and (1,1'-biphenyl-4-yl)piperazine trifluoroacetate (0.780 g). The mixture was stirred overnight at room temperature. The mixture was then partitioned between ethyl acetate and brine. The layers were separated and the organic layer was washed four times with brine, dried over anhydrous magnesium sulfate and concentrated. EPO <DP n="95"/>"The resulting crude mixture was stirred in hot MeOH to remove impurities and the remaining solid was collected and dried to give 0.34 g of the title compound: MS (ESI+) for C23H19CIN4O1S1 m/z 435.25 (M+H)+.1H NMR (400 MHz, CDCI3). delta 3.6 to 4.2 (m, 8H) 7.3 to 7.67 (m.11 H). To a mixture of the pyrimidine of Example 40 (0.4 g) in THF/DMF (20/8 ml_) was added diisopropylethylamine (0.44 ml_) and the TFA salt of Example 15 (0.780 g). The mixture was stirred overnight at room temperature. The mixture was then partitioned between ethyl acetate and brine. The layers were separated and the organic layer was washed four times with brine, dried over anhydrous magnesium sulfate and concentrated. The resulting crude mixture was stirred in hot methanol to remove impurities and the remaining solid was collected and dried to give 0.34 g of the title compound: MS (ESI+) for C23H19CIN4OS m/z 435.25 (M+H)+. 1H NMR (400 MHz, CDCI3). delta 3.6-4.2 (m, 8H) 7.3-7.67 (m, 11H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; chloroform; | EXAMPLE 8 2,4-Bis(N-methylphenylamino)thieno(2,3-d)pyrimidine 2,4-Dichlorothieno[2,3-d]pyrimidine (2 g, 0.00975 mol) and N-methylaniline (5 ml) were heated in an oil bath at 150° for 2 hours. The reaction mixture was dissolved in chloroform (200 ml) and extracted with 2N hydrochloric acid (3*100 ml). The chloroform solution was then washed with sodium carbonate solution, dried over magnesium sulphate, filtered and evaporated to give an oil. The oil was purified by chromatography using dichloromethane as eluant. The solid obtained was recrystallized from ether/petroleum ether (b.p. 40°-60°) to give the title compound, (1.2 g) m.p. 85°-87°. | |
In dichloromethane; chloroform; | Example 8 2,4-Bis(N-methylphenylamino)thieno(2,3-d)pyrimidine 2,4-Dichlorothieno[2,3-d]pyrimidine (2 g, 0.00975 mol) and N-methylaniline (5 ml) were heated in an oil bath at 150° for 2 hours. The reaction mixture was dissolved in chloroform (200 ml) and extracted with 2N hydrochloric acid (3x100 ml). The chloroform solution was then washed with sodium carbonate solution, dried over magnesium sulphate, filtered and evaporated to give an oil. The oil was purified by chromatography using dichloromethane as eluant. The solid obtained was recrystallized from ether/petroleum ether (b.p. 40-60°) to give the title compound, (1.2 g) m.p. 85-87°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aniline; In diethyl ether; ethanol; | (b) 2-Chloro-4-(phenylamino)thieno[2,3-d]pyrimidine 2,4-Dichlorothieno[2,3-d]pyrimidine (3.2 g, 0.0156 mol) and aniline (2.9 g, 0.0311 mol) in ethanol were stirred at room temperature for 20 hours. The solvent was evaporated under reduced pressure to give an oil. The oil was treated with diethyl ether to give a solid, aniline hydrochloride. The filtrate was evaporated under reduced pressure to give the product as a solid, (3.74 g). Recrystallization (0.7 g) from methanol gave a pure sample of the title compound, (0.53 g), m.p. 149°-151°. | |
With aniline; In diethyl ether; ethanol; | (b) 2-Chloro-4-(phenylamino)thieno[2,3-d]pyrimidine 2,4-Dichlorothieno[2,3-d]pyrimidine (3.2 g, 0.0156 mol) and aniline (2.9 g, 0.0311 mol) in ethanol were stirred at room temperature for 20 hours. The solvent was evaporated under reduced pressure to give an oil. The oil was treated with diethyl ether to give a solid, aniline hydrochloride. The filtrate was evaporated under reduced pressure to give the product as a solid, (3.74 g). Recrystallization (0.7 g) from methanol gave a pure sample of the title compound, (0.53 g), m.p. 149-151°. |
Tags: 18740-39-1 synthesis path| 18740-39-1 SDS| 18740-39-1 COA| 18740-39-1 purity| 18740-39-1 application| 18740-39-1 NMR| 18740-39-1 COA| 18740-39-1 structure
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P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
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 |
Sorry,this product has been discontinued.
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