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CAS No. : | 5509-65-9 |
Formula : | C6H5F2N |
M.W : | 129.11 |
SMILES Code : | C1=CC=C(C(=C1F)N)F |
MDL No. : | MFCD00007655 |
InChI Key : | ODUZJBKKYBQIBX-UHFFFAOYSA-N |
Pubchem ID : | 79647 |
GHS Pictogram: | ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301+H311+H331-H315-H319-H226 |
Precautionary Statements: | P501-P261-P270-P240-P210-P233-P243-P241-P242-P271-P264-P280-P370+P378-P337+P313-P305+P351+P338-P361+P364-P303+P361+P353-P332+P313-P301+P310+P330-P304+P340+P311-P403+P233-P403+P235-P405 |
Class: | 3(6.1) |
UN#: | 1992 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 30.76 |
TPSA ? Topological Polar Surface Area: Calculated from | 26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.4 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 2.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.93 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.04 |
Solubility | 1.17 mg/ml ; 0.0091 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.59 |
Solubility | 3.3 mg/ml ; 0.0256 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.56 |
Solubility | 0.357 mg/ml ; 0.00277 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) | 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 | -6.07 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 | 2.0 |
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 |
---|---|---|
88% | at 40℃; for 1.5 h; | B. A solution of 5.1 g (40 mmol) of 2,6-difluoroaniline, 10 mL of alcohol solvent and a few crystals of naphthalene (liquid chromatography internal standard) was placed in a 50 mL flask and heated to 40°C. Solid 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine (2.67 g, 10 mmol) was added with stirring under nitrogen and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. The mixture was cooled to ambient temperature and the solids were recovered by filtration, washed with 10 mL of 2-propanol and then water, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 4 to 6 in the following table. |
84.6% | at 25 - 45℃; for 5.5 - 8 h; | A jacketed 250 mL (milliliter) round bottom flask equipped with a stirrer, condenser, and nitrogen inlet and outlet was loaded with 49.1 g (grams), 0.38 mol (mole) of 2,6-difluoroaniline and 25 g of 1,2-propanediol. The mixture was warmed to 35°C by heating the jacket fluid and a solution of 30.3 g of 93 percent purity (0.10 mol) of 2-chlorosulfonyl-8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine in 30.2 g of dichloromethane was added portionwise with stirring under a nitrogen blanket over 3.5 hours. A solid began to form in about one hour and all of the chlorosulfonyl starting material was consumed in 5.5 hours. The resulting mixture was cooled to 20°C and filtered, collecting the solids. The solids were washed 2x40 mL with methanol and then with 112 g of water. The white solid obtained after drying was found to be the title compound with a purity of greater than 99 percent and to amount to 34.2 g (88.9 percent of theory); The preparation of the title compound was carried out as in Example 1 except that some of the parameters were varied. When the reaction was carried out at 25, 35, and 45°C, the time to complete disappearance of 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine and the recovered yield of title compound were 6.5 hours/86.5 percent of theory, 5.5 hours/87.9 percent of theory, and 4.9 hours/84.6 percent of theory, respectively. When the amount of 1,2-propanediol was 1.88, 0.95, and 0.48 grams per gram of 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c]-pyrimidine, the time to complete disappearance of the latter was 3, 5, and 8 hours, respectively. |
83% | at 40℃; for 1.5 h; | B. A solution of 5.1 g (40 mmol) of 2,6-difluoroaniline, 10 mL of alcohol solvent and a few crystals of naphthalene (liquid chromatography internal standard) was placed in a 50 mL flask and heated to 40°C. Solid 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine (2.67 g, 10 mmol) was added with stirring under nitrogen and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. The mixture was cooled to ambient temperature and the solids were recovered by filtration, washed with 10 mL of 2-propanol and then water, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 4 to 6 in the following table. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sodium perborate; In acetic acid; at 80 - 90℃; for 1h; | Step 1: A mixture of sodium perborate tetrahydrate (65 g, 422 mmol) in glacial acetic acid (250 mL) was stirred at 80 C. 2,6-Difluoroaniline (11.0 g, 85 mmol) in glacial acetic acid (50 mL) was added slowly to the mixture. The temperature was maintained between 80-90 C. for 1 hour. The cooled reaction mixture was poured into water and extracted twice with diethyl ether. The combined organic layers were washed with a dilute solution of sodium bicarbonate, dried over anhydrous magnesium sulfate and evaporated. The residue was purified via Biotage chromatography (FlasH90i, silica, 10% THF/hexane) and the product washed with hexane to afford 2,6-difluoronitrobenzene (7.0 g) (52%). MS (ESI) m/z 160 ([M+H]+). |
52% | With sodium perborate; In acetic acid; at 80 - 90℃; for 1h; | Step 1: A mixture of sodium perborate tetrahydrate (65 g, 422 mmol) in glacial acetic acid (250 mL) was stirred at 80 C. 2,6-Difluoroaniline (11.0 g, 85 mmol) in glacial acetic acid (50 mL) was added slowly to the mixture. The temperature was maintained between 80-90 C. for 1 hour. The cooled reaction mixture was poured into water and extracted twice with diethyl ether. The combined organic layers were washed with a dilute solution of sodium bicarbonate, dried over anhydrous magnesium sulfate and evaporated. The residue was purified via Biotage chromatography (FlasH90i, silica, 10% THF/hexane) and the product washed with hexane to afford 2,6-difluoronitrobenzene (7.0 g) (52%). MS (ESI) m/z 160 ([M+H]+). |
With sodium perborate; acetic acid; at 80 - 90℃; for 1h; | 2,6-Difluoroaniline (11.0 g, 85 mmol) in glacial acetic acid (50 mL) was added slowly to a stirred suspension of sodium perborate tetrahydrate (65 g, 422 mmol) in glacial acetic acid (250 mL) at 80 C. The temperature was maintained between 80-90 C. for 1 hour. The cooled reaction mixture was poured into water and extracted twice with diethylether and the combined organic layers were washed with a dilute solution of sodium bicarbonate, dried (MgSO4) and evaporated. The residue was purified by silica gel column chromatography (Hexane:THF, 9:1) and the product washed with hexane to afford 2,6-difluoronitrobenzene (7.0 g) which was used without further examination. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Iodine monochloride; In acetic acid; at 20℃; for 0.25h; | 2, 6-Difluorobenzenamine (3. 0g, 22.56 mmoles) was dissolved in acetic acid (10 ml). Iodine monochloride (3.581g, 22.56 mmoles) was added to the solution. The mixture was stirred for 15 minutes at room temperature. After evaporation of the solvent, the residue was treated with an aqueous solution of sodium carbonate. The aqueous solution was extracted with dichloromethane. The organic extract was dried over MgS04 and was evaporated. Yield: 95% of intermediate 33. |
95% | Example A1; a) Preparation of intermediate 1; 2,6-difluorobenzeneamine (3.0g, 22.56 mmoles) was dissolved in acetic acid (10 ml).Iodine monochloride (3.58lg, 22.56 mmoles) was added to the solution. The mixturewas stirred for 15 minutes at room temperature. After evaporation of the solvent, theresidue was treated with an aqueous solution of sodium carbonate. The aqueoussolution was extracted with dichloromethane. The organic extract was dried overMgSCU and was evaporated. Yield : 95% of intermediate 1. | |
51% | With silver(I) nitrite; iodine; In dichloromethane; at 0 - 20℃; for 1h; | Step 1: 4-Amino-3,5-difluoro-benzonitrile; To a suspension of iodine (5.59g, 22.0mmol) and AgNO2 (6.85g, 22.0mmol) in EPO <DP n="79"/>methylene chloride was added a solution of 2,6-difluoroaniline (2.58g, 20.0mmol) in methylene chloride at O0C, and the mixture was stirred for 30min at O0C and 30min at ambient temperature. The reaction was quenched with Na2S2O3. The reaction solution was extracted with methylenechloride, washed with water and brine, dried over anhyd. MgSO4, filtered and concentrated under reduced pressure. The obtained liquid was column-chromatographed (hexane/ethylacetate = 15/1) to yield a yellow solid (2.57mg, 51%). |
With Iodine monochloride; In acetic acid; | Step 3: 60 g of 2,6-difluoroaniline was dissolved in 180 ml of acetic acid. A solution containing 75 g of iodine chloride dissolved in 48 ml of acetic acid was added dropwise therein, and then agitated at 80 C. for 2 hours. The reaction solution was poured into water, and the resulting deposited crystals were filtrated and washed with water. The crystals were recrystallized with methanol, vacuum distilled (125 C./22 mmHg), and recrystallized again with methanol to obtain 57 g of 2,6-difluoro-4-iodoaniline. | |
With pyridine; Iodine monochloride; In chloroform; water; acetic acid; | Step 3: 2,6-Difluoroaniline (38 g) was dissolved in acetic acid (120 ml), and then pyridine (25 g) was added thereto, followed by stirring. Then, a mixture of iodine monochloride (50 g) with acetic acid (30 ml) was added dropwise thereto. After stirring at room temperature for 1 hour, the reaction solution was further stirred at 70 to 80 C. for 2 hours. Then, the reaction solution was poured into water, and the precipitated crystals were filtered, followed by washing with water. The resulting crystals were dissolved in chloroform, and then washed with water twice, further with 10% potassium hydroxide aqueous solution twice, and furthermore with water twice, followed by distilling off chloroform. The residue was distilled under reduced pressure (b.p. 120 to 130 C./20 mmHg), and then recrystallized from methanol to give 4-iodo-2,6-difluoroaniline (44 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.2% | Under nitrogen protection,Add to a 500mL four-neck reaction flask100mL of acetonitrile and 12.9g (0.1moL) of 2,6-difluoroaniline,Stir down to -20 C,A drop of dimethyl sulfide 3.1g (0.05moL),After dripping, stir for 30min.Then slowly dropwise add 26.67 g of N-chlorosuccinimide in acetonitrile solution.(Contains 6.67 g of N-chlorosuccinimide, 0.05 moL),After dropping, continue to react for 1 ~ 2h,Then slowly add 27.9g (0.3moL) of 3-methylpyridine,After stirring for 1h,56.6g of2-chlorosulfonyl-8-fluoro-5-methoxy [1,2,4] triazole[1,5-c] pyrimidine in acetonitrile(Containing 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4] triazole [1,5-c] pyrimidine26.6g, 0.1moL) slowly added to the above reaction solution,Finished in 1h, then,Stir at room temperature for 1h,The temperature was increased to 40 C, and the reaction was performed for 3 to 4 hours.HPLC traced the 2,6-difluoroaniline content to <0.5% to end the reaction.After the reaction is over,Reduce the temperature of the reaction solution to below 0 C,Add 250 g of dilute acid water (containing 41.7 g of 35% by weight hydrochloric acid),Acidified to pH <2,Precipitation of a large amount of solids,Stir for 1h, suction filter,Filter cake washedRinse with a small amount of methanol, dry,33.8 g of diflusulfuron was obtained as a white powder,The yield was 94.2% and the purity was 98.5% (HPLC). | |
88% | In propylene glycol; at 40℃; for 1.5h;Product distribution / selectivity; | B. A solution of 5.1 g (40 mmol) of 2,6-difluoroaniline, 10 mL of alcohol solvent and a few crystals of naphthalene (liquid chromatography internal standard) was placed in a 50 mL flask and heated to 40C. Solid 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine (2.67 g, 10 mmol) was added with stirring under nitrogen and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. The mixture was cooled to ambient temperature and the solids were recovered by filtration, washed with 10 mL of 2-propanol and then water, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 4 to 6 in the following table. |
84.6 - 88.9% | In propylene glycol; dichloromethane; at 25 - 45℃; for 5.5 - 8h;Product distribution / selectivity; | A jacketed 250 mL (milliliter) round bottom flask equipped with a stirrer, condenser, and nitrogen inlet and outlet was loaded with 49.1 g (grams), 0.38 mol (mole) of 2,6-difluoroaniline and 25 g of 1,2-propanediol. The mixture was warmed to 35C by heating the jacket fluid and a solution of 30.3 g of 93 percent purity (0.10 mol) of 2-chlorosulfonyl-8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine in 30.2 g of dichloromethane was added portionwise with stirring under a nitrogen blanket over 3.5 hours. A solid began to form in about one hour and all of the chlorosulfonyl starting material was consumed in 5.5 hours. The resulting mixture was cooled to 20C and filtered, collecting the solids. The solids were washed 2x40 mL with methanol and then with 112 g of water. The white solid obtained after drying was found to be the title compound with a purity of greater than 99 percent and to amount to 34.2 g (88.9 percent of theory); The preparation of the title compound was carried out as in Example 1 except that some of the parameters were varied. When the reaction was carried out at 25, 35, and 45C, the time to complete disappearance of 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine and the recovered yield of title compound were 6.5 hours/86.5 percent of theory, 5.5 hours/87.9 percent of theory, and 4.9 hours/84.6 percent of theory, respectively. When the amount of 1,2-propanediol was 1.88, 0.95, and 0.48 grams per gram of 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c]-pyrimidine, the time to complete disappearance of the latter was 3, 5, and 8 hours, respectively. |
83% | In ethylene glycol; at 40℃; for 1.5h;Product distribution / selectivity; | B. A solution of 5.1 g (40 mmol) of 2,6-difluoroaniline, 10 mL of alcohol solvent and a few crystals of naphthalene (liquid chromatography internal standard) was placed in a 50 mL flask and heated to 40C. Solid 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine (2.67 g, 10 mmol) was added with stirring under nitrogen and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. The mixture was cooled to ambient temperature and the solids were recovered by filtration, washed with 10 mL of 2-propanol and then water, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 4 to 6 in the following table. |
82% | In 1,1,1-trichloroethanol; at 45℃; for 2h;Product distribution / selectivity; | A. A 4.8 g (18 mmol) sample of 2-chlorosulfonyl-8-- fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine was placed in a 50 mL round bottom flask and then the following were added with stirring under nitrogen: 10 mL of an alcohol solvent, 12.9 g (100 mmol) of 2,6-difluoroaniline, and a few crystals of naphthalene (liquid chromatography internal standard). The mixture was heated to the desired temperature and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. When the reaction was complete, the mixture was cooled to 0 to 5C over a 30-min period and the solids were recovered by filtration, washed with cold solvent, washed with 0.5 N aqueous hydrochloric acid, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 1 to 3 in the table below. |
79% | To a solution of 3.87 grams (0.03 mol) of 2,6-difluoroaniline in 5.4 grams of propylene glycol was added a solution of 5.73 grams (0.02 mol) of 8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonyl chloride (SC) in 7 grams of methylene chloride over 1 hour. The SC solution was added in about 0.5 mL portions every 5-10 minutes. The temperature of the resulting mixture was maintained at less than 25 C. during the addition of the SC. After stirring the reaction mixture for another 1 hour at room temperature, 2.20 grams (0.02 mol) of triethylamine was added over 2.45 hours using a syringe pump. The reaction mixture was stirred at room temperature overnight and then was diluted with 5 g of water over 15 minutes. The resulting mixture was cooled to about 5 C. with an ice bath and then filtered. The collected white solid was rinsed with 15 mL of 7:3 (v/v) methanol-water and then dried at 50 C. to provide 5.44 g (74%) of florasulam (97.7 wt %). An additional 5% yield (total yield 79%) of florasulam was detected in the aqueous filtrate. | |
68% | In 2,2,2-trifluoroethanol; at 40℃; for 2.5h;Product distribution / selectivity; | A. A 4.8 g (18 mmol) sample of 2-chlorosulfonyl-8-- fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine was placed in a 50 mL round bottom flask and then the following were added with stirring under nitrogen: 10 mL of an alcohol solvent, 12.9 g (100 mmol) of 2,6-difluoroaniline, and a few crystals of naphthalene (liquid chromatography internal standard). The mixture was heated to the desired temperature and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. When the reaction was complete, the mixture was cooled to 0 to 5C over a 30-min period and the solids were recovered by filtration, washed with cold solvent, washed with 0.5 N aqueous hydrochloric acid, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 1 to 3 in the table below. |
68% | In 2-methoxy-ethanol; at 40℃; for 3h;Product distribution / selectivity; | B. A solution of 5.1 g (40 mmol) of 2,6-difluoroaniline, 10 mL of alcohol solvent and a few crystals of naphthalene (liquid chromatography internal standard) was placed in a 50 mL flask and heated to 40C. Solid 2-chlorosulfonyl-8-fluoro-5-methoxy[1,2,4]triazolo-[1,5-c]pyrimidine (2.67 g, 10 mmol) was added with stirring under nitrogen and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. The mixture was cooled to ambient temperature and the solids were recovered by filtration, washed with 10 mL of 2-propanol and then water, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 4 to 6 in the following table. |
67% | In 2-methoxy-ethanol; at 30℃; for 3h;Product distribution / selectivity; | A. A 4.8 g (18 mmol) sample of 2-chlorosulfonyl-8-- fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine was placed in a 50 mL round bottom flask and then the following were added with stirring under nitrogen: 10 mL of an alcohol solvent, 12.9 g (100 mmol) of 2,6-difluoroaniline, and a few crystals of naphthalene (liquid chromatography internal standard). The mixture was heated to the desired temperature and the disappearance of the chlorosulfonyl starting material was monitored by high pressure liquid chromatography. When the reaction was complete, the mixture was cooled to 0 to 5C over a 30-min period and the solids were recovered by filtration, washed with cold solvent, washed with 0.5 N aqueous hydrochloric acid, and dried. The recovered title compound product was over 99 percent pure. The results are given as Runs 1 to 3 in the table below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With formic acid; In ethanol; at 20℃; for 3h; | General procedure: To a stirred solution of 3,5-dichlorosalicylaldehyde (2.00 g,10.47 mmol) in ethanol (20 mL) was slowly added 2,6-difluoroaniline (1.37 g, 10.47 mmol) at room temperature in the presence of trace amount of formic acid as a catalyst. The reaction mixture was stirred at room temperature for 3 h. Orange crystals were formed and then filtered. The product was obtained in 64%yield (2.74 g). 1H NMR data (500.13 MHz, CDCl3, 298 K): δ 13.77(s, 1H, OH), 8.87 (s, 1H, NCH), 7.48 (d, 4JHH 2.5, 1H, salicyl-H), 7.31(d, 4JHH 2.5, 1H, salicyl-H), 7.23e7.16 (m, 1H, aniline-H), 7.06e6.98(m, 2H, aniline-H). 13C NMR data (125.77 MHz, CDCl3, 298 K):δ 166.50 (HCN), 157.61 (d, CF), 156.22 (COH), 155.57 (d, CF), 133.61(salicyl-CH), 130.50 (salicyl-CH), 128.15 (t, aniline-CN), 124.14(t, CCHN), 123.90 (CCl), 123.35 (CCl), 120.68 (aniline-CH), 112.64(d, aniline-CH). Elemental analysis for C13H7Cl2F2NO: C, 51.68; H,2.34; N, 4.64%. Found C, 51.89; H, 2.31; N, 4.66%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With phosphorus trichloride; In toluene; at 100.0℃; for 72h; | To a stirred solution of 9 <strong>[397308-78-0]4-hydroxy-2-(methylthio)pyrimidine-5-carboxylic acid</strong> (5 g, 26.88 mmol, 1.0 eq) in 100 mL of 24 Toluene was added 394 2,6-difluoroaniline (3.81 g, 29.55 mmol, 1.1 eq) and 91 PCl3 (25 mL). Reaction was allowed to stir at 100 C. for 72 h. Progress of reaction was monitored by LCMS. After consumption of starting material, solvent was removed under reduced pressure, residue was diluted with diethyl ether (100 mL) and 10 mL of MeOH. Solid was filtered out and dried under vacuum to obtain 7 g (88%) of 393 N-(2,6-difluorophenyl)-4-hydroxy-2-(methylthio)pyrimidine-5-carboxamide. (0473) LCMS: 298 [M+1]+ |
Tags: 5509-65-9 synthesis path| 5509-65-9 SDS| 5509-65-9 COA| 5509-65-9 purity| 5509-65-9 application| 5509-65-9 NMR| 5509-65-9 COA| 5509-65-9 structure
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P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
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. |
P271 | Use only outdoors or in a well-ventilated area. |
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. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
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. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
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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