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CAS No. : | 37045-73-1 | MDL No. : | MFCD03094037 |
Formula : | C7H10N2O2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UQRRCQRFQGOHAI-UHFFFAOYSA-N |
M.W : | 186.23 | Pubchem ID : | 2734262 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 49.12 |
TPSA : | 80.57 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.14 cm/s |
Log Po/w (iLOGP) : | 0.69 |
Log Po/w (XLOGP3) : | 0.42 |
Log Po/w (WLOGP) : | 1.54 |
Log Po/w (MLOGP) : | 0.05 |
Log Po/w (SILICOS-IT) : | -0.36 |
Consensus Log Po/w : | 0.47 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.5 |
Solubility : | 5.93 mg/ml ; 0.0318 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.68 |
Solubility : | 3.9 mg/ml ; 0.0209 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.4 |
Solubility : | 0.735 mg/ml ; 0.00394 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
69% | With iron; ammonium chloride In methanol; water at 70℃; Inert atmosphere | A solution ofN-(3-nitrophenyl)methanesulfonamide (2.6 g, 12.0 mmol, Eq: 1.00), iron (3.38 g, 60.5 mmol, Eq: 5.03) and ammonium chloride (6.48 g, 121 mmol, Eq: 10.1) in methanol (40 mL)/water (20 mL) was heated at 70°C o/n. The reaction mixture was filtered over Celite. The filtrate was concentrated, diluted with ethyl acetate, washed with brine 2x, dried over sodium sulfate, and chromatographed (1 15g Analogix, 20 to 40percent> EtO Ac/hex) to give 1.55 g (69percent>) of desired product as an orange solid. |
65.95% | With hydrogen In tetrahydrofuran; methanol | Step: 3A - 2Synthesis of N-(3-Amino-phenyl)-methanesulfonamide.Procedure:Pd-C was added to a solution of N-(3-Nitro-phenyl)-methanesulfonamide (900mg, 6.5217mmol) in MeOH(10 ml) and THF (10 ml) and the reaction mixture was subjected to hydrogenation overnight. The reaction was monitored by the TLC (50percent EtOAc: hexane). The resulting reaction mixture was filtered through celite, concentrated to afford 800mg (65.95percent yield) of N-(3-Amino-phenyl)-methanesulfonamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With iron; ammonium chloride; In methanol; water; at 70℃; under 760.051 Torr;Inert atmosphere; | A solution ofN-(3-nitrophenyl)methanesulfonamide (2.6 g, 12.0 mmol, Eq: 1.00), iron (3.38 g, 60.5 mmol, Eq: 5.03) and ammonium chloride (6.48 g, 121 mmol, Eq: 10.1) in methanol (40 mL)/water (20 mL) was heated at 70C o/n. The reaction mixture was filtered over Celite. The filtrate was concentrated, diluted with ethyl acetate, washed with brine 2x, dried over sodium sulfate, and chromatographed (1 15g Analogix, 20 to 40%> EtO Ac/hex) to give 1.55 g (69%>) of desired product as an orange solid. |
65.95% | With hydrogen;palladium on activated charcoal; In tetrahydrofuran; methanol; | Step: 3A - 2Synthesis of N-(3-Amino-phenyl)-methanesulfonamide.Procedure:Pd-C was added to a solution of N-(3-Nitro-phenyl)-methanesulfonamide (900mg, 6.5217mmol) in MeOH(10 ml) and THF (10 ml) and the reaction mixture was subjected to hydrogenation overnight. The reaction was monitored by the TLC (50% EtOAc: hexane). The resulting reaction mixture was filtered through celite, concentrated to afford 800mg (65.95% yield) of N-(3-Amino-phenyl)-methanesulfonamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methoxy-ethanol; at 80℃; | A mixture of intermediate 43 (prepared according to A2. c-6) (0. 0002 mol), N- (3-aminophenyl) methane sulfonamide (0. 0004 mol) in 2- methoxyethanol (2 ml) was stirred at least overnight at at least 80C and then the crude mixture was purified by high-performance liquid chromatography. The product fractions were collected and the solvent was evaporated (Genevac). The obtained residue was dissolved in CH30H and then the solvent was evaporated (Genevac), yielding compound 202. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In DMF (N,N-dimethyl-formamide); at 25℃; for 4h; | Example 33 5-Methyl-4-[[3-[(methylsulfonyl)amino]phenyl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic Acid Methyl Ester Phosphorus oxychloride was combined with Example 19 (30 mg, 0.14 mmol) and heated to 100 C. for 15 hrs. The melt was cooled and concentrated to remove excess reagent, then extracted with ethyl acetate (20 mL). The extract was washed with sat aqueous NaHCO3, (10 mL) dried over MgSO4 and concentrated in vacuo to provide chlorinated compound Example 27. The residue was dissolved in DMF (2 mL) and 3(methylsulfonylamino)aniline (54 mg, 0.3 mmol) was added. The reaction mixture was stirred for 4 hrs under argon at 25 C. The crude reaction mixture was purified by preparative HPLC. The material obtained appeared to be a salt of the desired compound. The material was dissolved in ethyl acetate and washed with saturated aqueous NaHCO3. Evaporation of the solvent gave 24 mg (40%) of Example 33. MS: [M+H]+=376.2; 1H NMR (d-DMSO): delta 8.89 (s, 1H), 8.14 (s, 1H), 7.95 (s, 1H), 7.55 (s, 1H), 7.38 (s, 1H), 7.34-7.32 (m, 2H), 7.01 (d, J=8.0 Hz, 1H), 3.81 (s, 3H), 3.02 (s, 3H), 2.82 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 2,6-dimethylpyridine; In N,N-dimethyl acetamide; at 130℃; for 4h; | To trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)- 3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3- d] pyrimidin-5-yl ester 70 (3.00 g) obtained in Step 6 and N-(3- aminophenyl) methanesulfonamide 44 (1.14 g) were added N,N- dimethylacetamide (6.00 ml) and 2,6-lutidine (0.712 ml), and the mixture was stirred at 130C for 4 hrs. After allowing to cool to room temperature, methanol/water [1: 2 (volume ratio), 18.0 ml] was added.under stirring. The crystals were collected by filtration and dried to give N-{3-[1-(2-fluoro-4-iodophenyl)- 3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3- d] pyrimidin-5-ylamino]phenyl}methanesulfonamide 71 (3.13 g, yield 98%) as a pale-gray solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 2,6-dimethylpyridine; In N,N-dimethyl acetamide; at 130℃; for 3.5h; | To trifluoromethanesulfonic acid 3-cyclopropyl-l-(2-fluoro- 4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro- pyrido [2,3-d]pyrimidin-5-yl ester 43 (30.0 g) obtained in the same manner in Example 4-2, Step 6 to be mentioned later and N- (3-aminophenyl) methanesulfonamide 44 (10.9 g) were added N,N- dimethylacetamide (60.0 ml) and 2,6-lutidine (6.82 ml), and the mixture was stirred at 130C for 3.5 hrs. After allowing to cool to room temperature, methanol (60 ml) was added with stirring and the mixture was stirred for 2 hrs. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-l-(2-fluoro-4- iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro- pyrido [2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 45 (30.5 g, yield 96%) as colorless crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With toluene-4-sulfonic acid; In ethanol; | EXAMPLE 2 Synthesis of Dye 2 Synthesis of 1-(3-methanesulfonamidoanilino)-1,2-dicyanoethylene. 3-Methanesulfonamidoaniline (11.7 g, 0.063 mmol) and 2-cyano-1,1,1-trimethoxyethane (11.8 g, 0.082 mol) were combined in a 100-mL round-bottomed flask, and heated to 140 C. with stirring in a pre-heated oil bath until the mixture became a homogeneous melt. A few crystals of p-toluenesulfonic acid were added to the melt, causing vigorous bubbling in the reaction mixture as the methanol by-product boiled away. Heating at 140 C. continued at atmospheric pressure for 15 minutes, then under vacuum at approximately 20 mm for another 15 minutes to remove the remaining methanol. The mixture was cooled to 25 C. under vacuum to form a brown-colored glass. Trituration with anhydrous ethanol (50 mL) gradually produced a granular solid. The mixture was cooled, and the product was collected by filtration and washed with cold ethanol to yield 14.2 g (84% yield) of methyl 2-cyano-N-(3-methanesulfonamido)-phenylacetimidate as an off-white powder, m.p. 118-120 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; hydrogen;palladium-charcoal; In tetrahydrofuran; pyridine; alpha-picoline; methanol-tetrahydrofuran; water; | EXAMPLE 12 Preparation of 3-Methanesulfonamido-2'-octanamido-4'-(2,4,6-triisopropylbenzenesulfonamido)diphenylamine The following reaction was carried out: STR45 A mixture of meta-methanesulfonamidoaniline (1.86 grams, 0.01 mole) and 2-fluoro-5-(2,4,6-triisopropylbenzenesulfonamido)nitrobenzene (4.29 grams, 0.01 mole) in 25 ml of alpha-picoline was refluxed for 29 hours. This mixture was poured into a mixture of 100 grams of ice and 100 ml of 1N hydrochloric acid, and the separated oil extracted with 100 ml of ethyl acetate. The extract was washed with water, dried by means of anhydrous sodium sulfate, and freed of solvent. The resulting oil was chromatographed on Woelm's silica gel using methylene chloride as the eluent. The column held material was eluted with 1:1 parts by volume methylene chloride-ethyl acetate, freed of solvent, and characterized as 3-methanesulfonamido-2'-nitro-4'-(2,4,6-triisopropylbenzenesulfonamido)diphenylamine. This compound was identified by nuclear magnetic resonance. 2.9 grams of the oily product were dissolved in 150 ml of 1:1 methanol-tetrahydrofuran and reduced with hydrogen over a palladium-charcoal catalyst by means of a Parr apparatus. After removal of catalyst and solvent, the solid product was characterized by nuclear magnetic resonance as 3-methanesulfonamido-2'-amino-4'-(2,4,6-triisopropylbenzenesulfonamido)diphenylamine. 1.5 grams (0.003 mole) of this compound were then dissolved in 20 ml of dry pyridine and reacted at 5 C. with 6.5 grams of octanoyl chloride in 20 ml of dry tetrahydrofuran. After 18 hours at 25 C., the reaction mixture was poured into ice and 20 ml of concentrated hydrochloric acid, and the separated oil extracted with methylene chloride. The extract was washed with 10 percent sodium bicarbonate in water, dried, and freed of solvent. The resulting oil was purified by pressure liquid chromatography to yield 1.3 grams of a glass that was recrystallized from ether-hexane to give white leaflets. The desired product was characterized by nuclear magnetic resonance and had a melting point of 146 to 148 C. A sample of this compound was oxidized in butyl acetate with potassium ferricyanide in pH 10 buffer, yielding a yellow dye possessing a maximum absorption of 429 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methoxy-ethanol; at 110℃; for 2h; | N-(3-Aminophenyl)methanesulfonamide (7.4 g, 40 mmol) is added to a solution of 6-Amino- 2-bromo-pyrimidin-4-ol (7.6 g, 40 mmol) (described in Hirayama et al., Chemical & Pharmaceutical Bulletin (1976), 24(1), 26-35) in 2-methoxythoxyethanol (240 ml_). The resulting solution is heated at 1100C for 2 h. The mixture is cooled to room temperature and the solvent is evaporated off under reduced pressure. Water is then added and the suspension is filtered, washed twice with water to give, after drying in high vacuum, the title compound as a grey solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methoxy-ethanol; at 110℃; for 15h; | N-(3-Aminophenyl)methanesulfonamide (4.1 g, 22 mmol) is added to a solution of 2-bromo- 1 ,9-dihydro-purin-6-one (4.30 g, 20 mmol) in 2-methoxythoxyethanol (120 mL). The resulting solution is heated at 1100C for 15h. The mixture is cooled to room temperature and the solvent is evaporated off under reduced pressure. Water is then added and the suspension <n="18"/>is filtered, washed twice with water to give, after drying in high vacuum, the title compound as a pale pink solid, MS: 321 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With acetic acid; In butan-1-ol; at 150℃; for 0.666667h;Microwave irradiation; | Intermediate 6 (41 mg, 0.121 mmol), N-(3-amino-phenyl)-methane sulfonamide (68 mg, 0.365 mmol), glacial acetic acid (8 mul, 0.121 mmol) and n-butanol (1.3 ml) were combined and irradiated at 150 0C for 40 minutes in a Biotage 1-60 microwave reactor. The reaction mixture was evaporated and then purified by preparative LCMS (low pH buffer) to give a white solid (42 mg, 57%). 1H nuMR (400 MHz, DMSO-Cf6) delta ppm 0.53 - 0.61 (m, 2 H), 0.86 - 0.93 (m, 2 H), 1.49 - 1.57 (m, 1 H), 1.80 - 1.89 (m, 2 H), 3.00 (s, 3 H), 3.27 - 3.35 (m, 2 H), 3.53 - 3.61 (m, 2 H), 6.92 - 6.97 (m, 1 H), 7.13 (dd, 7=4.8, 3.9 Hz, 1 H), 7.27 - 7.34 (m, 1 H), 7.36 - 7.42 (m, 2 H), 7.58 (s, 1 H), 7.68 - 7.76 (m, 2 H), 8.46 - 8.60 (m, 2 H), 9.86 (s, 1 H), 10.20 (br. s, 1 H); m/z (ES+APCI)+: 487 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; for 1h; | Example 237Preparation of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-phenyl)-amide To a stirred solution of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (100 mg, 0.22 mmol) in methylene chloride (10 mL), HATU (Aldrich, 83 mg, 0.22 mmol) was added followed by the addition of DIPEA (0.20 mL) and 3-aminophenyl-methanesulfonamide (Aldrich, 0.25 mmol). The mixture was stirred at rt 1 hr. The reaction was quenched with addition of water. The mixture was extracted with methylene chloride (2×10 mL) and the extracts were dried with magnesium sulfate. The solvent was removed and the residue was purified on an ISCO machine (40 g column, eluent, 35-80% EtOAc/hexanes) to give a white solid. 64 mg.MS (ES+) m/z Calcd: [(M+H)+]: 634. found: 634 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 8h; | General procedure: 4-Aminobenzoic acid (10a) (0.80 g, 5.89 mmol) and potassium carbonate (0.62 g, 5.89 mmol) were added to a solution of compound 9 (0.5 g, 1.96 mmol) in DMF (1 mL). The reaction mixture was stirred at rt for 8 h, quenched into cold water and neutralized (pH 4.5-5.0) with dilute hydrochloric acid. The precipitate formed was filtered, washed with cold water and dried. The solid thus obtained was recrystallized from a mixture of chloroform and methanol to afford compound 11a (0.24 g, 35%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | In isopropyl alcohol; at 80℃; for 24h; | Example 20Synthesis of N-(3-((5-(isoquinolin-6-yl)oxazol-2-yl)amino)phenyl)methanesulfonamide The general synthetic scheme for CH2002 (compound 59) is found in FIG. 40. Compound 1, compound 10, compound 11, compound 12, compound 13, and compound 14 were prepared as described above. Compound 59: N-(3-((5-(isoquinolin-6-yl)oxazol-2-yl)amino)phenyl)methanesulfonamideA mixture of 2-chloro-5-(isoquinolin-6-yl)oxazole 14 (0.15 g, 0.652 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.121 g, 0.649 mmol) in 2-propanol (20 mL) was heated to 80 C. for 12 h with stirring. Additional one more equivalent of <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.121 g, 0.649 mmol) was added to reaction mixture and heated to 80 C. for further 12 h with stirring. Upon cooling, solvent was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide N-(3-((5-(isoquinolin-6-yl)oxazol-2-yl)amino)phenyl)methane sulfonamide 59 (0.09 g, 38% yield) as pale yellow solid. MS (ES) m/z 381 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | In isopropyl alcohol; at 80℃; for 14h; | Compound 24: tert-butyl 2-(2-((3-(methylsulfonamido)phenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylateA mixture of tert-butyl 2-(2-chlorooxazol-5-yl)-1H-indole-1-carboxylate 21 (0.281 g, 0.883 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.321 g, 1.723 mmol) in 2-propanol (20 mL) was heated to 80 C. for 14 h with stirring. Upon cooling, solvent was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide tert-butyl 2-(2-((3-(methylsulfonamido) phenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylate 24 (0.221 g, 54% yield) as solid. MS (ES) m/z 469 (M+H+).(NOTE: In this case, the entire product is isolated as free base due to sulfonamide functionality. No hydrochloride salt is observed). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | In isopropyl alcohol; at 80℃; for 14h; | Example 11Synthesis of N-(3-((5-(4-(trifluoromethyl)phenyl)oxazol-2-yl)amino)phenyl)methanesulfonamide The general synthetic scheme for CH1232 (compound 33) is found in FIG. 21. Compound 30 and compound 31 were prepared as described above. Compound 33: N-(3-((5-(4-(trifluoromethyl)phenyl)oxazol-2-yl)amino)phenyl)methanesulfonamideA mixture of 2-chloro-5-(4-(trifluoromethyl)phenyl)oxazole 31 (0.599 g, 2.42 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.451 g, 2.42 mmol) in 2-propanol (20 mL) was heated to 80 C. for 14 h with stirring. Upon cooling, solvent was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide N-(3-((5-(4-(trifluoromethyl)phenyl)oxazol-2-yl)amino)phenyl)methane sulfonamide 33 (0.393 g, 41% yield) as a solid. MS (ES) m/z 398 (M+H+).(NOTE: In this case, the entire product is isolated as free base due to phenolic functionality. No hydrochloride salt is observed) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In isopropyl alcohol; at 80℃; for 18h; | Compound 40: N-(3-((5-(4-cyano-3-fluorophenyl)oxazol-2-yl)amino)phenyl)methanesulfonamideA mixture of 4-(2-chlorooxazol-5-yl)-2-fluorobenzonitrile 39 (0.225 g, 1.01 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.188 g, 1.01 mmol) in 2-propanol (20 mL) was heated to 80 C. for 18 h with stirring. Reaction mixture was evaporated and crude product was purified using MPLC (Biotage) silica column (Biotage) (Acetone/hexane as an eluent) to provide N-(3-((5-(4-cyano-3-fluorophenyl)oxazol-2-yl)amino)phenyl)methane sulfonamide 40 (0.319 g, 84% yield) as a solid. MS (ES) m/z 373 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | In isopropyl alcohol; at 80℃; for 18h; | Example 18Synthesis of tert-butyl 5-fluoro-2-(2-((3-(methylsulfonamido)phenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylate The general synthetic scheme for CH1281 (compound 52) is found in FIG. 36. Compound 46, compound 47, compound 48, compound 49, and compound 50 were prepared as described above. Compound 52: tert-butyl 5-fluoro-2-(2-((3-(methylsulfonamido)phenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylateA mixture of tert-butyl 2-(2-chlorooxazol-5-yl)-5-fluoro-1H-indole-1-carboxylate 50 (0.314 g, 0.934 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.174 g, 0.934 mmol) in 2-propanol (20 mL) was heated to 80 C. for 18 h with stirring. Upon cooling, solvent was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide tert-butyl 5-fluoro-2-(2-((3-(methylsulfonamido)phenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylate 52 (0.11 g, 25% yield) as solid. MS (ES) m/z 487 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Compound 54: N-(3-thioureidophenyl)methanesulfonamideTo a stirred solution of thiocarbonyl diimidazole 53 (TCDI, 1.80 g, 10.10 mmol) in anhydrous CH2Cl2 (25 mL) at 0 C. was added DCM solution of commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (1.00 g, 5.37 mmol) at 0 C. Reaction was stirred for 3 hours at room temperature. Reaction was again cooled to 0 C. and ammonia-in-methanol (excess, 20 mL) was added dropwise. After stirring for 14 hours at room temperature, it was concentrated and water (20 mL) was added, stirred for 1 hour. Solid product was filtered, washed with water. Solid was dried under vacuum to obtain N-(3-thioureidophenyl)methanesulfonamide 54 (1.14 g, 87% yield). Resulting product was further used without further purification. MS (ES) m/z 246 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44%; 40% | In isopropyl alcohol; at 80℃; for 18h; | Example 3Synthesis of N-(3-((5-(4-cyanophenyl)oxazol-2-yl)amino)phenyl)methanesulfonamide The general synthetic scheme for CH1150 (compound 7) is found in FIG. 5. Compound 1 and compound 2 were prepared as described in Example 2, above. Compound 7: N-(3-((5-(4-cyanophenyl)oxazol-2-yl)amino)phenyl)methanesulfonamideA mixture of 4-(2-chlorooxazol-5-yl)benzonitrile 2 (0.20 g, 0.98 mmol) and commercially available <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 6 (0.182 g, 0.98 mmol) in 2-propanol (20 mL) was heated to 80 C. for 18 h with stirring. Upon cooling, a white solid precipitated out which was filtered off, washed with 2-propanol, and dried. This was then triturated with ether and filtered to yield the title product, a white solid, as the hydrochloride salt of 7 (0.14 g, 40%). Free amine containing filtrate was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide 7 (0.151 g, 44% yield) as pale yellow solid. MS (ES) m/z 355 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In isopropyl alcohol; at 120℃; for 1.5h;Sealed tube; | <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (382 mg, 2.05 mmol) and l-chloro-6-methyl- 5-nitroisoquinoline (500 mg, 2.25 mmol) obtained in of Preparation Example 2 were dissolved in isopropanol (10 mL), and the reaction solution was sealed, followed by stirring for 1.5 hours at 120C. The reaction mixture was cooled to room temperature, and the resulting solid was filtered under reduced pressure, followed by washing with isopropanol and diethyl ether. The filtered solid was dried under vacuum conditions to obtain the title compound (752.8 mg, 99%). -NMR Spectrum (300 MHz, DMSO-ifc): delta 9.80 (brs, 1H), 8.75 (d, 1H), 8.05 (d, 1H), 7.75 (m, 2H), 7.58 (d, 1H), 7.35 (t, 1H), 6.94 (d, 1H), 6.89 (d, 1H), 3.04 (s, 3H), 2.50 (s, 3H) MS(ESI+, m/z): 373 [M+H]+ |
99% | In isopropyl alcohol; at 120℃; for 1.5h;Sealed tube; | <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (382 mg, 2.05 mmol) and 1-chloro-6-methyl-5-nitroisoquinoline (500 mg, 2.25 mmol) obtained in <Step 4> of Preparation Example 2 were dissolved in isopropanol (10 mL), and the reaction solution was sealed, followed by stirring for 1.5 hours at 120 C. The reaction mixture was cooled to room temperature, and the resulting solid was filtered under reduced pressure, followed by washing with isopropanol and diethyl ether. The filtered solid was dried under vacuum conditions to obtain the title compound (752.8 mg, 99%). 1H-NMR Spectrum (300 MHz, DMSO-d6): delta 9.80 (brs, 1H), 8.75 (d, 1H), 8.05 (d, 1H), 7.75 (m, 2H), 7.58 (d, 1H), 7.35 (t, 1H), 6.94 (d, 1H), 6.89 (d, 1H), 3.04 (s, 3H), 2.50 (s, 3H) MS (ESI+, m/z): 373 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 20℃; | General procedure: The solution of cyanuryl chloride (1 mmol, 1 equiv.) in THF (20 ml) was stirred,cooled to -10 C, and aniline (1 mmol, 1 equiv.) in THF (6 ml) and DIEA (3.6 mmol, 1.2equiv.) was added dropwise. The mixture was stirred at this temperature for 0.5-2 h. Uponcompletion, monitored by TLC, another aniline (1 mmol, 1 equiv.) was added. The mixturewas stirred under room temperature for 2-12 h. After the solvent was removed under reducedpressure the resulting solid was collected by filtration, dried and crystallised or purified bysilica gel column chromatography to get the desired product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In isopropyl alcohol; at 80℃; for 0.25h;Microwave irradiation; | General procedure: A mixture of 4-chloroquinazoline (23a-c,[1] 23d-f, 31-33[3]) (0.5 mmol) and the appropriate aniline (0.5 mmol) in i-PrOH (1 mL) was microwave irradiated at 80 C (power set point 60 W; ramp time1 min; hold time 15 min). After cooling, the obtained precipitate was collected by filtration to give compounds 5-18 and 33-35 as hydrochlorides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In isopropyl alcohol; at 80℃; for 0.25h;Microwave irradiation; | General procedure: A mixture of 4-chloroquinazoline (23a-c,[1] 23d-f, 31-33[3]) (0.5 mmol) and the appropriate aniline (0.5 mmol) in i-PrOH (1 mL) was microwave irradiated at 80 C (power set point 60 W; ramp time1 min; hold time 15 min). After cooling, the obtained precipitate was collected by filtration to give compounds 5-18 and 33-35 as hydrochlorides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In dichloromethane; at 0 - 20℃; under 760.051 Torr;Inert atmosphere; | To a solution of <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (.5 g, 2.68 mmol, Eq: 1.00) in DCM (10 mL) at OoC, was added di(lH-imidazol-l-yl)methanethione (574 mg, 3.22 mmol, Eq: 1.2). The reaction mixture was gradually warmed to room temperature overnight. The reaction mixture was concentrated and chromatographed (40g Analogix, 10% to 30% EtO Ac/hex) to give 557 mg (91%>) of desired product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In 1,2-dichloro-ethane; at 120℃; for 2h;Inert atmosphere; Sealed tube; | General procedure: To a stirred solution of 11 (13.14 mmol) in 1,2-dichloroethane (240 mL) were added appropriate substituted anilines (19.71 mmol) and AcOH (13.14 mmol), and the mixture was heated to reflux for 2 h under nitrogen atmosphere. The reaction mixture was cooled to 0 C, and MeOH (60 mL) and THF (20 mL) were added. To it, (AcO)3BHNa (26.20 mmol) or NaBH4 (52.56 mmol) was added portionwise, and then the reaction mixture was allowed to warm to room temperature and stirred for an additional 3 h. The pH of the reaction mixture was adjusted to 7-8 at 0 C with 1 NHCl, and then the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2× 300 mL). The combined organic layers was washed with brine (300 mL) and dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel to afford the titled compounds as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26.4% | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 5h; | 5-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinic acid (15.0 mg, 0.0350 mmol) was added to <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (7.73 mg, 0.0420 mmol) and a solution of HATU (19.7 mg, 0.0520 mmol) and DIPEA (0.0180 mL, 0.104 mmol) in DMF (0.5 mL) was added. The reaction mixture was stirred for 5 hours at room temperature. The volatile components were removed under high vacuum and the residue was purified by reverse phase preparative HPLC (Condition 36 as described in general methods) to afford N-(3-(methylsulfonamido)phenyl)-5-(5-phenyl-4-((pyridin-2- ylmethyl)amino)phthalazin-1-yl)nicotinamide (5.79 mg, 26.4%) as a white solid. LCMS (Condition 37): retention time 1.63 min, [M+l] = 602.1, purity 95.02%. 1H NMR (400 MHz, DMSO-d6) delta 3.01 (s, 3 H), 4.67 (d, J= 4.4 Hz, 2 H), 6.34 (t, J= 4.4 Hz, 1 H), 6.95- 6.99 (m, 1 H), 7.21-7.24 (m, 1 H), 7.28 (d, J= 8.0 Hz, 1 H), 7.30 (t, J= 8.0 Hz, 1 H), 7.50-7.58 (m, 6 H), 7.68-7.77 (m, 3 H), 7.90-7.94 (m, 2 H), 8.22-8.24 (m, 1 H), 8.61 (t, J = 2.0 Hz, 1 H), 9.05 (d, J= 2.0 Hz, 1 H), 9.26 (d, J= 2.0 Hz, 1 H), 10.60 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; water; for 24h;Reflux; | 2,4-Dichloro-5-fluoropyrimidine (50 mg, 0.3 mmol) was dissolved in a mixture of MeOH (1 ml) and H2O (0.1 ml). 3-methylsulfonylaminoaniline (300 mg, 1.5 mmol) was added and the mixture was refluxed for 24 hours (70 C. oil-bath temperature). The mixture was cooled to 22 C., concentrated to dryness under reduced pressure and subjected to column chromatography on silica gel (CHCl3-Acetone, 9:1) to give N2,N4-bis[3-methylsulfonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamine. 1H NMR (DMSO-d6+CD3OD): delta 8.01 (d, 1H, J=3.5 Hz), 7.46-7.68 (m, 4H), 7.49 (t, 1H, J=8.2 Hz), 7.13 (t, 1H, J=8.2 Hz), 6.89 (dd, 1H, J=2.4, 8.2 Hz), 6.72 (m, 1H), 2.95 (s, 3H), 2.91 (s, 3H); LCMS: purity: 97.2%; MS (m/e): 466.89 (M+, 100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; for 48h;Reflux; | General procedure: Procedure B: A mixture of substituted 2,4-dichloropyrimidine (1.0 equiv.), and substituted aniline (1.0-1.05 equiv.), and DIPEA (1.2 equiv.) in isopropanol (0.1 M) was stirred and heated at reflux. The reaction time, work-up, and product isolation procedure are described below. |
100% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; for 48h;Reflux; | This was prepared from 2,4-dichloro-5-methylpyrimidine (0.326 g), N-(3- aminophenyl)methanesulfonamide (0.372 g) and DIPEA (0.418 mL) using procedure B (reaction time, 48 h) and isolated in the same way as MA2-030 to give the title compound MA2-035 as a gray solid (0.374 g, 100%). Mp: 191-193 C. NMR (400 MHz, DMSO-ifc): delta 9.85 (s, 1H, disappeared on D2O shake), 8.95 (s, 1H, disappeared on D2O shake), 8.06 (d, / = 0.9 Hz, 1H), 7.54 (t, / = 1.9 Hz, 1H), 7.35 (dd, / = 8.4, 1.5 Hz, 1H), 7.30 (t, / = 8.0 Hz, 1H), 6.91 (ddd, / = 7.8, 2.0, 1.1 Hz, 1H), 3.05 (s, 3H), 2.17 (s, 3H). HPLC-MS (ESI+): m/z 315.2 [40%, (M35C137 +], 313.1 [100%, (M35C135C1+H)+]. Procedure B A mixture of substituted 2,4-dichloropyrimidine (1.0 equiv.), and substituted aniline (1.0-1.05 equiv.), and DIPEA (1.2 equiv.) in isopropanol (0.1 M) was stirred and heated at reflux. The reaction time, work-up, and product isolation procedure are described below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 100℃; for 1h;Microwave irradiation; | 4-Chloro-6,7-dimethoxy-quinazoline (100 mg, 0.4500 mmol) and 1H-indazol-6-amine (59.27 mg, 0.4500 mmol) were mixed in MeCN (2 mL) and irradiated in a CEM microwave at 100 C for one hour. The reaction mixture was allowed to cool and then passed through a short pad of silica. After concentration of the filtrate, the resultant solid was washed sequentially with acetonitrile and diethyl ether and dried in vacuo to give 16 (0.13g, 81%) as a light brown solid. 1H NMR (DMSO-d6) delta 13.21 (br s, 1H), 11.37 (s, 1H), 8.84 (s, 1H), 8.30 (s, 1H), 8.12 (s, 1H), 7.94 (s, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.41 (d, J=8.6 Hz, 1H), 7.34 (s, 1H), 4.03 (s, 3H), 4.01 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43%; 19% | With tris[2-phenylpyridinato-C2,N]iridium(III); In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Irradiation; | Under nitrogen or argon, 0.4 mmol, 0.2mmol, Ir(ppy) 3(2mg) and DMF1 ml was added to the reaction flask, followed by blue LED lights(7W) at room temperature irradiation straight trivalent iodine reagent completeconversion of the reaction. Add 10 ml of saturated Na 2CO 3Aqueous solution, andextracted three times with ethyl acetate, the organic layer was washed with water andonce with saturated brine, dried over anhydrous Na 2SO 4The organic layer was dried.Column chromatography (eluent: petroleum ether 60-90: ethyl acetate = 10: 1-5: 1) to Ethyl acetate = 10: 1-5: 1) to give the product , S; Yield 43%.Rate of 19%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | mg (0.23 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2, 6-dimethylimidazo[1 ,2-a]pyridine-3-carboxylic acid (Example 21A), 112 mg (0.29 mmol) of O-(7-azabenzotriazol- 1 -yl)-N,N,N?N?-tetramethyluronium hexafluorophosphate (HATU) and 197 tl (1.13 mmol) of N,N-diisopropylethylamine (DIPEA) were initially charged in 0.8 ml of DMF. The mixture was stirred at RT for 20 mm, and 55 mg (0.29 mmol) of <strong>[37045-73-1]N-(3-aminophenyl)methanesulphonamide</strong> were then added and the mixture was stirred at 60 C. for 1 h. The reaction mixture was diluted with acetonitrile, water/TFA was added and the mixture was purified by preparative HPLC (RP18 colunm, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions were concentrated and purified once more by preparative thick-layer chromatography (mobile phase:dichloromethane/methanol=70/1). This gave 3.4 mg (3% of theory; purity 98%) of the title compound.10781] LC-MS (Method 2): R=0.80 mm10782] MS (ESpos): mlz=501 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.1% | With triethylamine; In tetrahydrofuran; for 12h;Reflux; | General procedure: A solution of compound 2 (0.5 mmol, 1 equiv) with <strong>[37045-73-1]N-(3-aminophnyl)mthanesulfonamide</strong> or N-methyl-2-aminobenzamide (1 eq) and triethylamine (1,2 eq) in THF was stirred at reflux for 12 h. The solvent was evaporated under vacuum, and the crude residue was purified by silica gel column chromatography eluted with a mixture of dichloromethane and methanol. N-(3-((3,6-dichloro-1,2,4-triazin-5-yl)amino)phenyl)methanesulfonamide (3). White solid, mp 182 C, 106.7 mg (64.1%). 1H NMR (250 MHz, CDCl3) delta: 3.07 (s, 3H), 7.01 (d, J = 8.0 Hz, 1H), 7.40 (m, 2H), 7.62 (s, H), 9.97 (s, 1H), 10.23 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80 mg | With potassium dihydrogenphosphate; In tert-butyl alcohol; at 0 - 80℃; for 16h; | Example 68 (2568) N-(3-((7-Chloro-5-hydroxy-1 ,1 -dioxido-2H-benzore1H ,2,41thiadiazin-3- yl)amino)phenyl)methanesulfonamide (2569) (2570) To a stirred solution of <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (143 mg) in tert-butanol (10 ml_) was added potassium dihydrogen phosphate (105 m). The reaction mixture was cooled to 0 C and 3-bromo-7-chloro-5-hydroxy-2H-benzo[e][1 ,2,4]thiadiazine 1 ,1 -dioxide (lnt-3, 200 mg, 0.642 mmol) was added slowly. The reaction mixture was then heated to 80 C and stirred for 16 hr. The reaction mixture was cooled to RT, diluted with cold water, and the resulting solid was collected by filtration to afford the crude product (200 mg), which was washed with diethyl ether (4ml_) and dried under reduced pressure. The crude product was purified by preparative reversed phase HPLC (Xterra C18 19 x 250 mm) using a gradient of 10-50% 10 mM ammonium bicarbonate (aq) in acetonitrile. The appropriate fractions were concentrated under reduced pressure to afford the final product (80 mg). LCMS m/z 417.03 (M+H). NMR after D20 exchange (400 MHz, DMSO-c/6) delta ppm 3.03 (s, 3 H) 6.98 (dt, J=6.85, 2.17 Hz, 1 H) 7.08 (d, J=2.19 Hz, 1 H) 7.19 (d, J=2.19 Hz, 1 H) 7.28 - 7.47 (m, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With trifluoroacetic acid; In isopropyl alcohol; for 18h;Sealed tube; Heating; | General procedure: A mixture of 2-chloro-4-(ary)pyrimidine (7-12) (0.23 mmol), amine (0.23 mmol), TFA (0.4 ml) in isopropanol was heated in a sealed tube at 100C for 18 h.The reaction mixture was cooled to room temperature and diluted with 1M NaOH until is neutral. The precipitate was filtered, washed with deionized water, isopropanol, EtOAc, and dried under air or purified by silica gel column chromatography to give the desired product and >95% pure analytical by HPLC analysis. Reaction yields ranged from 30-70% (Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
600 mg | With hydrogenchloride; In 1,4-dioxane; at 0 - 20℃; for 3h; | To a solution of tert-butyl (3-(methylsulfonamido)phenyl)carbamate (1 .0 g) in 1 ,4-dioxane (10 mL) at 0 C was added HCI (4 M in 1 ,4-dioxane, 4.37 mL). The reaction mixture was allowed to warm to RT and stirred for 3 hr. The reaction mixture was diluted with EtOAc (80 mL) and washed with saturated sodium bicarbonate (aq) (2 x 100 mL) followed by saturated brine. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the titled compound (600 mg). LCMS m/z 186.90 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
162 mg | With pyridine; In dichloromethane; at 0 - 20℃; for 16h; | To a solution of <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> (200 mg) in DCM wad added pyridine (0.434 mL). The reaction mixture was cooled to 0 C and 3-carbamoyl-4- hydroxybenzene-1 -sulfonyl chloride (lnt-1 , 253 mg) was added portionwise. The reaction mixture was allowed to warm to RT and stirred for 16 hr. The reaction mixture was diluted with water and the resulting solid was collected by filtration to afford the crude product. The crude product was purified by preparative reversed phase HPLC (Kromosil phenylhexyl, 25x150 mm) using a gradient of 10-40% acetonitrile in 5 mM ammonium bicarbonate (aq). The desired fractions were concentrated under reduced pressure to afford the titled compound (162 mg). LCMS m/z 386.03 (M+H)+. NMR (400 MHz, DMSO-c/6) delta ppm 2.70 - 3.06 (m, 3 H) 6.83 (t, J=8.33 Hz, 2 H) 6.95 - 7.09 (m, 2 H) 7.16 (t, J=7.34 Hz, 1 H) 7.74 (d, J=8.1 1 Hz, 1 H) 7.90 - 8.17 (m, 1 H) 8.33 (br. s., 1 H) 8.49 (br. s., 1 H) 9.71 (br. s., 1 H) 10.18 (br. s., 1 H) 13.39 (br. s., 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69%; 11% | With oxygen; palladium diacetate; acetic acid; In dimethyl sulfoxide; at 70℃; for 18h;Schlenk technique; Molecular sieve; | Take a 25 mL Schlenk reaction tube, add 74 mg of 3-methanesulfonylaminoaniline, 9 mg of palladium acetate and 80 mg of molecular sieve.93 mg of ethyl 2-oxopropionate, 96 mg of acetic acid and 2 mL of dimethyl sulfoxide were injected, followed by a 200 mL oxygen balloon, and stirred at 70 C for 18 hours.After the reaction was completed, 15 mL of ethyl acetate was added to dilute the reaction mixture, and the filtrate was washed twice with 10 mL of brine, and the organic phase was separated. The aqueous phase was extracted with ethyl acetate. The organic phase was combined and purified by column chromatographyof Ethyl 6-Methanesulfonylamino-1H-indole-2-carboxylate pure product 78mg, yield 69%; ethyl 4-methanesulfonylamino-1H-indole-2-carboxylate pure product 1mg, yield 1 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.5% | With calcium bicarbonate; magnesium hydrogencarbonate; sodium dodecyl-sulfate; sodium carbonate; calcium chloride; magnesium chloride; In water; at -8 - 30℃; for 13.5h; | With mechanical agitation,In a 2000 mL four-necked flask of thermometerAdd 850mL of water,m phenylenediamine 108.0 g (1.0 mol),Sodium lauryl sulfate 1.9g,With good agitation,Was added to sodium carbonate solution and filtered calcium chloride on a number of m-sulfonamidoaniline,Magnesium chloride mixed wastewater (molar ratio of calcium chloride to magnesium chloride 9:11) is used as raw material.Prepared by adding 0.15% polyethylene glycol-1000,47.4 g of ultrafine calcium carbonate having an average particle diameter of 1 mum or less and an ultrafine magnesium carbonate binder (in which a molar ratio of calcium carbonate to magnesium carbonate is 9:11, a total of 0.520 mol)Stirring and cooling,Maintain 120.2 g (1.05 mol) of methylsulfonyl chloride dropwise at -8~-3 C.After the 5.0h drop,-2~3C insulation for 5.0h,Warm up to 25~30 C for 3.5h.Cool to below 10 C,filter,Ice water washing resulted in 183.2 g of methanesulfonamidoaniline in the product.The yield is 98.5%.The content is 98.2%,The unreacted raw material has a phenylenediamine content of 0.25%.The bis-methanesulfonylation by-product 1,3-bismethanesulfonylbenzene was 0.48%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.2% | With sodium carbonate; In water; at 100℃; for 0.5h; | In a 1000 mL four-necked flask with mechanical stirring and a thermometer,Add 700g of water,Methanesulfonamidoaniline 149g(content 80%, 0.64 mol), sodium carbonate 140 g (1.32 mol),Stir well and then as solution A,Transfered to the pipeline reactor by screw pump A,At the same time pumping liquid 1-chloropropane 143g (1.82mol),Solution A and 1-chloropropane are fed with screw pump A and screw pump B, respectively.The mass flow rate ratio of the control solution A to 1-chloropropane was 6.9:1.0.The pipeline reactor has a pipeline reaction section providing a chemical reaction site, and the solution A and 1-chloropropane are continuously reacted in the pipeline reaction section.Keep the temperature of the pipeline reaction section at 100 C,Control the residence time of the reaction solution for 30 min, cooling,Extracted with 800 mL of anisole,The combined organic phases are concentrated under reduced pressure.Obtaining dialkylaminomethanesulfonanilide157.6g,97.9%,The yield was 91.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.2% | With magnesium oxide; In water; at 115℃; for 1h; | In a 1000 mL four-necked flask with mechanical stirring and a thermometer,Add 700g of water, m-sulfonamidoaniline 149g(content 80%, 0.64 mol),Magnesium oxide 50g (1.25mol),Stir well and then as solution A,Transfered to the pipeline reactor by screw pump A,At the same time pumping liquid 1-chloro-2-methylpropane 185g (2.00mol),Solution A and 1-chloro-2-methylpropane are fed with screw pump A and screw pump B, respectively.The mass flow rate ratio of the control solution A to 1-chloro-2-methylpropane was 4.9:1.0.The pipeline reactor has a section of a pipeline reaction section that provides a place for chemical reaction to occur,Solution A and 1-chloro-2-methylpropane are continuously reacted in a pipeline reaction section.Keep the temperature of the pipeline reaction section at 115 C,Control the residence time of the reaction solution to 60 min, cooling,The chloroform was extracted in 800 mL, and the combined organic phases were concentrated under reduced pressure.Obtaining dialkylaminomethanesulfonanilide175.8g,97.3%,The yield was 92.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.5% | With calcium carbonate; In water; at 135℃; for 0.166667h; | In a 1000 mL four-necked flask with mechanical stirring and a thermometer,Add 700g of water,Methanesulfonamidoaniline 149g(content 80%, 0.64 mol),Calcium carbonate 150g (1.50mol),Stir well and then as solution A,Transfered to the pipeline reactor by screw pump A,At the same time pumping liquid 1-chlorohexane 163g (1.35mol),Solution A and 1-chlorohexane are fed with screw pump A and screw pump B, respectively.The mass flow rate ratio of the control solution A to 1-chlorohexane was 6.1:1.0.The pipeline reactor has a pipeline reaction section providing a chemical reaction site, and the solution A and 1-chlorohexane are continuously reacted in the pipeline reaction section.Keep the temperature of the pipeline reaction section at 135 C,Control the residence time of the reaction solution to 10 min,Cooled, extracted with 800 mL of 2-methyltetrahydrofuran.The combined organic phases are concentrated under reduced pressure.Obtaining dialkylaminomethanesulfonanilide214.1g,97.6%,The yield was 94.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate; In water; at 120℃; for 0.166667h; | In a 1000 mL four-necked flask with mechanical stirring and a thermometer,Add 700g of water, m-sulfonamidoaniline 149g(content 80%, 0.64 mol),Potassium carbonate 170g (1.23mol),Stir well and then as solution A,Transfered to the pipeline reactor by screw pump A,At the same time, 78.3 g (1.55 mol) of gaseous methyl chloride was introduced.Solution A and methyl chloride are fed as screw pump A and screw pump B, respectively.The mass flow rate ratio of the control solution A to methyl chloride was 13.0:1.0.The pipeline reactor has a section of a pipeline reaction section that provides a place for chemical reaction to occur,Solution A and methyl chloride are continuously reacted in the pipeline reaction section.Keep the temperature of the pipeline reaction section at 120 C,Control the residence time of the reaction solution to 10 min, cool, and extract 1000 mL of toluene.The combined organic phases are concentrated under reduced pressure.127.4 g of dialkylaminomethanesulfonanilide was obtained.The content is 98.4%,The yield was 93.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.8% | With sodium hydrogencarbonate; In water; at 90℃; for 0.833333h; | In a 1000 mL four-necked flask with mechanical stirring and a thermometer,Add 700g of water, m-sulfonamidoaniline 149g(content 80%, 0.64 mol), sodium bicarbonate 200 g (2.38 mol),Stir well and then as solution A,Transfered to the pipeline reactor by screw pump A,At the same time, 108 g (1.68 mol) of gaseous ethyl chloride was introduced.Solution A and ethyl chloride are fed as screw pump A and screw pump B, respectively.The mass flow rate ratio of the control solution A to ethyl chloride was 9.7:1.0.The pipeline reactor has a pipeline reaction section providing a chemical reaction site, and the solution A and the ethyl chloride are continuously reacted in the pipeline reaction section.Keep the temperature of the pipeline reaction section at 90 C,Control the residence time of the reaction solution for 50 min, cooling,Extracted with ethyl acetate 900 mL,The combined organic phases are concentrated under reduced pressure.146.8 g of dialkylaminomethanesulfonanilide was obtained.The content was 98.1%, and the yield was 94.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran;Reflux; Inert atmosphere; | General procedure: To a solution of N-[4-[5-(3-aminophenyl)-1,2,4-oxadiazol-3-yl]-3-chlorophenyl]-3-pyridinecarboxamide (VIc)(0.2 g, 0.51 mmol, 1 equiv) in THF (20 ml) was added phosgene(15wt % in toluene, 1.7 ml, 2.55 mmol, 5.0 equiv) and the reactionmixture was refluxed under N2 for 4 h. Upon the reactioncompletion as indicated by TLC the solution was concentratedunder reduced pressure, flushed with dry toluene. To theresulting residuewas added THF (20 ml), the appropriate aniline(0.77 mmol, 1.5 equiv) and DIPEA (0.132 g, 178 ml, 1.02 mmol, 2equiv) and the reaction mixture was refluxed under N2 overnight.Upon completion of the reaction as indicated by TLC, thesolution was concentrated, and the residue was purified bychromatography to give the desired final products (25-50). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.8% | With toluene-4-sulfonic acid; In 1-methyl-pyrrolidin-2-one;Heating; | General procedure: To a solution of 4-(benzylamino)-2-(methylsulfinyl)pyrimidine-5-carboxamide (4; 1.0 eq) and PTSA (1.1 eq)), in NMP was added differentsubstituted aryl amines (1.0 eq), at RT. The reaction mixture washeated at 100-110 C for 1-2 h. After completion of reaction, themixture was diluted with water and the compound was extracted inEtOAc. Organic layer was dried over sodium sulfate, filtered and concentratedunder vacuum to afford the crude product. Crude product waspurified by flash chromatography over silica gel (100-200 mesh) with2% MeOH/CHCl3 to provide the desired title product 5a-o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | In ethanol; at 150℃;Sealed tube; Microwave irradiation; | General procedure: To a MW vial, were successively added the appropriate <strong>[13720-94-0]ethyl 4-chloroquinoline-3-carboxylate</strong> derivative 4a-d (0.21 mmol), 3-aminobenzenesulfonamide(0.036 gm, 0.21 mmol), 3-amino-N-methylbenzenesulfonamide 8 (0.04 gm, 0.21 mmol), or N-(3-aminophenyl)methanesulfonamide 10 (0.04 gm, 0.21 mmol) and absolute ethyl alcohol(12 mL) at room temperature. The MW vial was sealed and heated under MW conditions for 30 min at 150 C. The mixture was evaporated in vacuo and the residue was extracted with EA and NaHCO3 (aq). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (SiO2, EA: n-Hex) to furnish quinolines5a-d, 9a-d and 11a-d, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In ethanol; at 150℃;Sealed tube; Microwave irradiation; | General procedure: To a MW vial, were successively added the appropriate ethyl 4-chloroquinoline-3-carboxylate derivative 4a-d (0.21 mmol), 3-aminobenzenesulfonamide(0.036 gm, 0.21 mmol), 3-amino-N-methylbenzenesulfonamide 8 (0.04 gm, 0.21 mmol), or <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 10 (0.04 gm, 0.21 mmol) and absolute ethyl alcohol(12 mL) at room temperature. The MW vial was sealed and heated under MW conditions for 30 min at 150 C. The mixture was evaporated in vacuo and the residue was extracted with EA and NaHCO3 (aq). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (SiO2, EA: n-Hex) to furnish quinolines5a-d, 9a-d and 11a-d, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In ethanol; at 150℃;Sealed tube; Microwave irradiation; | General procedure: To a MW vial, were successively added the appropriate ethyl 4-chloroquinoline-3-carboxylate derivative 4a-d (0.21 mmol), 3-aminobenzenesulfonamide(0.036 gm, 0.21 mmol), 3-amino-N-methylbenzenesulfonamide 8 (0.04 gm, 0.21 mmol), or <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 10 (0.04 gm, 0.21 mmol) and absolute ethyl alcohol(12 mL) at room temperature. The MW vial was sealed and heated under MW conditions for 30 min at 150 C. The mixture was evaporated in vacuo and the residue was extracted with EA and NaHCO3 (aq). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (SiO2, EA: n-Hex) to furnish quinolines5a-d, 9a-d and 11a-d, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | In ethanol; at 150℃;Sealed tube; Microwave irradiation; | General procedure: To a MW vial, were successively added the appropriate ethyl 4-chloroquinoline-3-carboxylate derivative 4a-d (0.21 mmol), 3-aminobenzenesulfonamide(0.036 gm, 0.21 mmol), 3-amino-N-methylbenzenesulfonamide 8 (0.04 gm, 0.21 mmol), or <strong>[37045-73-1]N-(3-aminophenyl)methanesulfonamide</strong> 10 (0.04 gm, 0.21 mmol) and absolute ethyl alcohol(12 mL) at room temperature. The MW vial was sealed and heated under MW conditions for 30 min at 150 C. The mixture was evaporated in vacuo and the residue was extracted with EA and NaHCO3 (aq). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (SiO2, EA: n-Hex) to furnish quinolines5a-d, 9a-d and 11a-d, respectively. |
Tags: 37045-73-1 synthesis path| 37045-73-1 SDS| 37045-73-1 COA| 37045-73-1 purity| 37045-73-1 application| 37045-73-1 NMR| 37045-73-1 COA| 37045-73-1 structure
[ 128263-66-1 ]
N-(4-(Aminomethyl)phenyl)methanesulfonamide hydrochloride
Similarity: 0.84
[ 36268-67-4 ]
4-(Methanesulfonylamino)benzonitrile
Similarity: 0.84
[ 456-64-4 ]
1,1,1-Trifluoro-N-phenylmethanesulfonamide
Similarity: 0.81
[ 128263-66-1 ]
N-(4-(Aminomethyl)phenyl)methanesulfonamide hydrochloride
Similarity: 0.84
[ 36268-67-4 ]
4-(Methanesulfonylamino)benzonitrile
Similarity: 0.84
[ 456-64-4 ]
1,1,1-Trifluoro-N-phenylmethanesulfonamide
Similarity: 0.81
[ 128263-66-1 ]
N-(4-(Aminomethyl)phenyl)methanesulfonamide hydrochloride
Similarity: 0.84
[ 36268-67-4 ]
4-(Methanesulfonylamino)benzonitrile
Similarity: 0.84
[ 456-64-4 ]
1,1,1-Trifluoro-N-phenylmethanesulfonamide
Similarity: 0.81
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
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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