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Structure of 1220910-89-3
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 1220910-89-3 |
Formula : | C21H17FN6O2 |
M.W : | 404.40 |
SMILES Code : | O=C(OCC1=CC=CC=C1)NC2=CC=C(C3=CC=C(C4=NN(C)N=N4)N=C3)C(F)=C2 |
MDL No. : | MFCD22418002 |
Boiling Point : | No data available |
InChI Key : | GIBJIBYBOVNDET-UHFFFAOYSA-N |
Pubchem ID : | 73014119 |
GHS Pictogram: | ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H315-H319-H228 |
Precautionary Statements: | P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅲ |
Num. heavy atoms | 30 |
Num. arom. heavy atoms | 23 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 7.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 107.98 |
TPSA ? Topological Polar Surface Area: Calculated from | 94.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 3.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 3.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 3.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 3.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 3.39 |
Log S (ESOL):? ESOL: Topological method implemented from | -4.69 |
Solubility | 0.00827 mg/ml ; 0.0000205 mol/l |
Class? Solubility class: Log S scale | Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from | -5.23 |
Solubility | 0.0024 mg/ml ; 0.00000594 mol/l |
Class? Solubility class: Log S scale | Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -7.57 |
Solubility | 0.0000108 mg/ml ; 0.0000000267 mol/l |
Class? Solubility class: Log S scale | Poorly 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) | Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | Yes |
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) | Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.25 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 3.35 |
* 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 |
---|---|---|
86.7% | Stage #1: With potassium <i>tert</i>-butylate; lithium tert-butoxide In tetrahydrofuran; acetonitrile at 25℃; for 2 h; Inert atmosphere Stage #2: for 3 h; | In a 1L three-necked bottle, 50 g of a compound of Formula X3, 400 ml of tetrahydrofuran and 400 ml of acetonitrile were added.Nitrogen gas, temperature 25°C, solids insolubleThen, 9.9 g of lithium tert-butoxide and 13.9 g of potassium tert-butoxide were added, and the solid matter dissolved.The reaction solution changed from colorless to yellow,After stirring for 2 hours, the reaction solution was added dropwiseR-(-)-glycidol butyric acid and compound of formula R 19.7 g,After completion of the addition, the reaction was incubated for 3 hours, and the sample was subjected to a TLC (developing solvent: chloroform/methanol = 10/1). After the spot of the compound of Formula X3 disappeared, the sample was dropped.Add dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, fully stir for 30 minutes, the water bath temperature is 35°C to 55°C, and the vacuum degree -0.07MPa to -0.1MPa is concentrated under reduced pressure to stop flow. |
85% | Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 1.41667 h; Inert atmosphere Stage #2: With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In tetrahydrofuran at 20℃; for 15 h; Inert atmosphere; cooling with ice | A 5-L, three-neck, round-bottom flask was equipped with an overhead stirrer, a thermocouple, a 500-mL addition funnel and a nitrogen-inlet adapter. The flask was dried with a heat gun under a flow of nitrogen to an internal temperature of 60°C. The flask was charged with intermediate 7 (110.0 g, 0.272 mol, AMRI lot No. DUG-AF-202Q)) and anhydrous THF (2.2 L, 20 vol). The slurry was stirred and a light green solution formed. The addition funnel was charged with 1.0 M lithium hexamethyldisilazide (299 mL, 0.286 mol, 1.05 eq.). The LiHMDS solution was added dropwise to the solution of intermediate 7 over approximately 25 minutes. A red solution formed. The solution was stirred one hour at room temperature and then DMPU (34.9 g, 0.272 mol, 1 eq) was added, and the mixture turned to a yellow slurry. The batch was cooled in an ice bath to 5.7°C. R-(-)-Glycidyl butyrate (41.25 g, 0.286 mol, 1.05 eq) was then added in one portion. The mixture was stirred in the ice bath for 0.5 hour and then was warmed to room temperature and stirred overnight. The reaction formed a tan slurry at this point, and HPLC analysis after 15 hours indicated that there was approximately 87percent TR-700, 1.6percent intermediate 7, and approximately 7percent of the butyrate ester of TR-700. A small amount of sodium methoxide in methanol (11 mL, 0.1 vol) was added, and the batch was stirred for 1 hour to remove the residual ester. The in-process HPLC analysis at this point showed there was approximately 90.7percent TR-700 and 0.2percent of the butyrate ester. The reaction was quenched by the addition of 10percent w/w ammonium chloride solution (1.1 L, 10 vol). A modest exothermic event from 22°C to 25°C was observed upon addition of the ammonium chloride solution. The two-phase mixture was distilled to a pot temperature of 700C (atmospheric pressure) to remove approximately 2.2 L of the THF. This formed a thick slurry which is diluted with water (550 mL, 5 volumes). The slurry was cooled to room temperature (23.6°C) and was filtered. The filter cake was washed with water (1.1 L, 10 vol) and methanol (550 mL, 5 vol) to give TR-700 as a white solid. The wet cake was dried overnight in a vacuum oven at 500C to give 89.7 g of TR-700 (89percent yield) that was 97.8percent (AUC) by HPLC analysis. The TR-700 was further purified by reslurrying in 2.7 L (30 vol) of 4: 1 methanol/water at 700C, cooling to 230C, filtering and washing with methanol (180 ml). This removed some of the over-alkylated product that is observed. The purified TR- 700 was recovered in 96percent yield (85percent overall yield), and the purity was improved to 98.4percent (AUC) by HPLC analysis. The palladium content was 10 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; tert.-butyl lithium; (R)-glycidyl butyrate In tetrahydrofuran at 0 - 30℃; for 15 h; Large scale | To the kettle was added tetrahydrofuran (20 L)And benzyl N- [3-fluoro-4- [6- (2-methyl- 2H- tetrazolium- 5 -yl) -3-pyridyl] phenyl] carbamateCompound (II) (1 Kg, 2.47 mol),0 ~ 30 ° C After mixing,1,3-Dimethyl-3,4,5,6-tetrahydro-2-pyrimidone was added sequentially (DMPU, 0.63 Kg, 4.94 mol, 2 equivalents),Lithium tert-butoxide (0.396 Kg, 4.94 mol, 2 equivalents)Add R-glycidyl butyrate(0.39 Kg, 2.72 mol, 1.1 equivalents)0 ~ 30 ° C for 15 hours.After the reaction,The reaction was quenched by adding a mass-volume ammonium chloride solution (1 Kg / 10 L)Concentrated under reduced pressure,The residue was added to methanol (10 L)Stirred for 0.5 hours to give suction filtration,The filter cake was washed with methanol,45 ~ 50 ° C under vacuum to give a white solid(5R) -3- (4- (6- (2-methyl- 2H- tetrazolium- 5-yl) -3-pyridyl) -3- fluorophenyl) -5-hydroxymethyl oxazoline -2-one Compound (III) (0.87 Kg, yield: 95percent). |
Tags: 1220910-89-3 synthesis path| 1220910-89-3 SDS| 1220910-89-3 COA| 1220910-89-3 purity| 1220910-89-3 application| 1220910-89-3 NMR| 1220910-89-3 COA| 1220910-89-3 structure
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P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
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P230 | Keep wetted |
P231 | Handle under inert gas. |
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P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
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P240 | Ground/bond container and receiving equipment. |
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P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
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P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
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P285 | In case of inadequate ventilation wear respiratory protection. |
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Code | Phrase |
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P378 | |
P380 | Evacuate area. |
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P391 | Collect spillage. Hazardous to the aquatic environment |
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P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
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P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
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P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
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P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
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H242 | Heating may cause a fire |
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H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
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H272 | May intensify fire; oxidizer |
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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 |
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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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