Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 5744-59-2 | MDL No. : | MFCD00085040 |
Formula : | C6H8N2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PXRXGHUTKHXUGF-UHFFFAOYSA-N |
M.W : | 140.14 | Pubchem ID : | 587757 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 35.41 |
TPSA : | 55.12 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) : | -6.81 cm/s |
Log Po/w (iLOGP) : | 0.89 |
Log Po/w (XLOGP3) : | 0.49 |
Log Po/w (WLOGP) : | 0.43 |
Log Po/w (MLOGP) : | -0.02 |
Log Po/w (SILICOS-IT) : | 0.14 |
Consensus Log Po/w : | 0.39 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -1.32 |
Solubility : | 6.68 mg/ml ; 0.0477 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.22 |
Solubility : | 8.5 mg/ml ; 0.0606 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.53 |
Solubility : | 41.3 mg/ml ; 0.294 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.62 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
81% | Stage #1: for 2 h; Reflux Stage #2: With ammonia In water at 0℃; |
A mixture of l-dimethyl-lH-pyrazole-S-carboxylic acid (10 g, 71.43 mmol) and SOCl2 (25.5 g, 214.29 mmol) was refluxed for 2 hr. The mixture was concentrated under vacuum. The residue was added with 200 mL of NH3-H2O dropwise with stirring at 0 °C. The solids were collected by filtration, resulted in 8 g (81percent) of l,5-dimethyl-lH-pyrazole-3- carboxamide as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.4% | b) Preparation of 1,5-Dimethyl Pyrazole 3-Carboxylic Acid To 9.8 g (58.3 mmoles) of the ethyl ester of 1,5-dimethyl pyrazole 3-carboxylic acid are added 50 ml of ethanol and 2.3 g (58.3 mmoles) of sodium hydroxide in 19.5 ml of water. 6.15 g of 1,5-dimethyl pyrazole 3-carboxylic acid are obtained in the form of colorless crystals (yield: 75.4%). M.p.=175 C. | |
75.4% | b) preparation of 1,5-dimethyl pyrazole 3-carboxylic acid. To 9.8 g (58.3 mmoles) of the ethyl ester of 1,5-dimethyl pyrazole 3-carboxylic acid are added 50 ml of ethanol and 2.3 g (58.3 mmoles) of sodium hydroxide in 19.5 ml of water. 6.15 g of 1,5-dimethyl pyrazole 3-carboxylic acid are obtained in the form of colorless crystals (yield: 75.4%). M.p.=175 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 20h; | To a stirred solution of 2-(4-[2-amino-5-chloro-4-(trifluoromethyl)phenyl]amino}phenyl)ethyl(4-methylphenyl)sulfonylcarbamate (step 2, 200 mg, 0.379 mmol) in dichloromethane (1.7 ml) was added a solution of <strong>[5744-59-2]1,5-dimethyl-1H-pyrazole-3-carboxylic acid</strong> (63.8 mg, 0.455 mmol) and N,N-diisoprppylethylamine (118 mg, 0.909 mmol) in dichloromethane (1.7 ml), then to the mixture was added a solution of HOBt (61.5 mg, 0.455 mmol) and EBTU (431 mg, 1.14 mmol) in DMF (2.5 ml), and the mixture was stirred at room temperature for 20 h. The mixture was quenched with water (100 ml). The whole was extracted with ethyl acetate (100 ml×3). The combined organic layer was washed with water (100 ml×3), brine (50 ml), dried (MgSO4), and concentrated. Purification by PTLC eluting with hexane/ethyl acetate (1:1) to afford 145 mg (59%) of the title compound as a red solid. [2115] 1H-NMR (CDCl3) delta: 8.70 (1H, s), 7.87 (2H, d, J=8.1 Hz), 7.79 (1H, s), 7.28 (2H, d, J=8.1 Hz), 7.04 (2H, d, J=8.3 Hz), 6.95 (2H, d, J=8.3 Hz), 6.72 (1H, s), 6.60 (1H, s), 4.22 (2H, t, J=6.8 Hz), 3.78 (3H, s), 2.84-2.80 (2H, m), 2.40 (3H, s), 2.30 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Compounds 41-70 were part of a parallel set prepared in library plate format according to General Procedure L, outlined below. ; L. General Procedure for Plate Preparation-Amide Formation XXI: Resin bound deprotected biarylphenol XVII (prepared from intermediate XII, boronates XIVd and XIVe, following general procedures D-F) was distributed into a 96 well plate, 10 mg of resin (0.013 mmol) per well. To the resin 400 mul of dichloromethane was added, followed by 100 mul of DIEA, followed by 0.13 mmol (10 equiv) of heterocyclic carboxylic acid XXa-XXn was added followed by 61 mg (0.13 mmol, 10 equiv) of PyBrop. The plate was shaken at room temperature for 24 hours, then drained and washed with dichloromethane, methanol/dichloromethane, dimethylformamide, methanol/dichloromethane and dichloromethane. The compounds were cleaved with TFA/dichloromethane (600 mul, 1:1) into a 96 deep well plate and submitted for testing without further purification. (Mass spec results obtained are shown in Table 4). Carboxylic Acids Het-COOH XX: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1 ,5-Dimethyl-1 /-/-pyrazole-3-carboxylic acid (54.2 mg) was dissolved in a solution of DMF (3 ml_), DIPEA (182 mul_) and HATU (201 mg), the reaction was stirred at room temperature for 15 mins. Intermediate 64 (150 mg) in DMF (1 ml.) was added and the reactions were stirred at 5O0C under nitrogen for 22 h. The reaction mixture was evaporated in vacuo and was partitioned between DCM and saturated sodium bicarbonate solution. The organic phase was collected and dried by passing through a hydrophobic frit and evaporated in vacuo. The crude material was purified using a 12 g silica ISCO cartridge eluting with a gradient of 5 - 100% EtOAc in cyclohexane to give the title compound. MS calcd for (C30H36N4O4S + H)+ : 549 MS found (electrospray) : (M+H)+ = 549 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | In tetrahydrofuran; N,N-dimethyl acetamide; N,N-dimethyl-formamide; | Example 85 Production of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,5-dimethyl-1H-pyrazole-3-carboxamide In the same manner as in Example 259 and using <strong>[5744-59-2]1,5-dimethyl-1H-pyrazole-3-carboxylic acid</strong> (145 mg, 1.0 mmol), tetrahydrofuran (5 mL), N,N-dimethylformamide (1 drop), oxalyl chloride (320 muL, 4.44 mmol), N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (250 mg, 0.77 mmol) and N,N-dimethylacetamide (7 mL) as starting materials, the title compound (57 mg, 17%) was obtained as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 0.76-0.86 (4H, m), 1.87-1.97 (1H, m), 2.27 (3H, s), 2.30 (3H, s), 3.83 (3H, s), 6.53 (1H, s), 6.97-7.06 (2H, m), 7.25-7.34 (1H, m), 7.61 (1H, d, J=2.3 Hz), 7.92-7.97 (1H, m), 8.02 (1H, d, J=9.5 Hz), 9.35 (1H, s), 11.07 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 22N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2-(4'- hydroxy-2'-(thiomorpholinomethyl)biphenyl-3-yloxy)nicotinamide HATU (0.062 g, 0.16 mmol) and DIPEA (0.114 mL, 0.66 mmol) were added to a solution of <n="71"/>1,5 -dimethyl- lH-pyrazole-3-carboxylic acid (0.023 g, 0.16 mmol) in acetonitrile (4 niL). The mixture was stirred for 10 min then a solution of N-((ls,4s)-4-aminocyclohexyl)-5-fluoro-2- (4'-hydroxy-2'-(thiomorpholinomethyl)biphenyl-3-yloxy)nicotinamide (0.100 g, 0.16 mmol) dihydrochloride in acetonitrile (4 mL) was added and the reaction stirred at RT for 2 days. 880 aqueous ammonia (~2 mL) was added, followed by enough methanol to bring the precipitated solids into solution (~2 mL). The mixture was stirred for a further 4 h then diluted with DCM and washed with water and saturated brine. The organic was evaporated to afford crude product. The crude product was purified by preparative HPLC on a Waters X- Bridge column using a 95-5% gradient of aqueous 0.2% TFA in acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compound as a cream-coloured foam. Yield: 63 mg.1H NMR (400 MHz, DMSO) delta 9.93 (br s, IH), 8.33 (d, J= 6.9 Hz, IH), 8.27 (d, J= 3.1 Hz, IH), 8.04 (dd, J= 7.8, 3.2 Hz, IH), 7.51 (t, J= 8.0 Hz, IH), 7.23 (d, J= 7.9 Hz, 2H), 7.18 - 7.11 (m, 3H), 7.05 - 7.04 (m, IH), 6.92 (d, J= 7.6 Hz, IH), 6.39 (s, IH), 4.28 - 4.23 (m, 2H), 3.99 - 3.95 (m, IH), 3.85 - 3.80 (m, IH), 3.74 (s, 3H), 2.87 - 2.61 (m, 4H), 2.26 (s, 3H), 1.75 - 1.62 (m, 8H). Remaining protons obscured by solvent peak. MS: [M+H]+=659.2 (calc=659.2816) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 2N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2-(4'- hydroxy-2'-(morpholinomethyl)biphenyl-3-yloxy)nicotinamide Step (a) N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2- (3-iodophenoxy)nicotinamideTo a solution of l,5-dimethyl-lH-pyrazole-3-carboxylic acid (0.123 g, 0.88 mmol) in dry DMF (10 mL) was added DIPEA (0.460 mL, 2.64 mmol) followed by HATU (0.334 g, 0.88 mmol). The mixture was allowed to stir for 10 min at RT. To this mixture was added N- ((ls,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy Nicotinamide (0.40Og, 0.88 mmol) and the mixture stirred overnight, poured onto water and the crude product collected by filtration, dried and used in step (c) without purification. [M+H]+ =577 (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 25℃; for 2h;Inert atmosphere; | Example 120N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-2-(4'-((dimethylamino)methyl)-2'-(morpholinomethyl)biphenyl-3-yloxy)-5-fluoronicotinamide HATU (116 mg, 0.30 mmol) was added in one portion to N-((ls,4s)-4-aminocyclohexyl)-2-(4'-((dimethylamino)methyl)-2'-(morpholinomethyl)biphenyl-3-yloxy)-5-fluoronicotinamide(170 mg, 0.25 mmol), 1,5 -dimethyl- lH-pyrazole-3-carboxylic acid (39.1 mg, 0.28 mmol) andDIPEA (0.221 mL, 1.27 mmol) in DMF (2 mL) at 250C under nitrogen. The resulting solution was stirred at 25 0C for 2 h. The reaction was diluted with methanol (2 mL) and acidified with HCl. The crude reaction was then purified on reverse phase HPLC 95/05MeOH/TFA. The title compound was obtained as a white solid after freeze drying. Yield: 132 mg1H NMR (300 MHz, DMSO) delta 8.36 (d, J = 7.1 Hz, IH), 8.28 (d, J = 3.1 Hz, IH), 8.05 (dd, J =8.0, 3.0 Hz, IH), 7.77 (s, IH), 7.67 - 7.52 (m, 3H), 7.48 (d, J = 7.9 Hz, IH), 7.22 (m, 3H),6.40 (s, IH), 4.33 (s, 6H), 3.96 (s, IH), 3.84 (s, IH), 3.75 (s, 3H), 3.66 (s, 4H), 2.79 (s, 8H),2.26 (s, 3H), 1.70 (m, 8H).MS: [M+H]+=684 (calc=684) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 129N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-2-(4'-(((3S,5R)-3,5- dimethylpiperazin-l-yl)methyl)-3'-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamide To a solution of l^-dimethyl-lH-pyrazole-S-carboxylic acid (32.0 mg, 0.23 mmol) in acetonitrile (3.00 mL) was added DIPEA (0.080 niL, 0.46 mmol) and HATU (87 mg, 0.23 mmol). After stirring for 5 min this solution was then added to a mixture of N-((ls,4s)-4- aminocyclohexyl)-2-(4'-(((3S,5R)-3,5-dimethylpiperazin-l-yl)methyl)-3'-hydroxybiphenyl-3- yloxy)-5-fluoronicotinamide, trihydrochloride (150 mg, 0.23 mmol) and DIPEA (0.080 mL, 0.46 mmol) in acetonitrile (3 mL). The mixture was left to stir at RT for 1 h. To this solution was then added 2mL of 0.88 NH3(aq) and the mixture was allowed to stir for 1 h. The reaction mixture was evaporated to dryness and the residue was then dissolved in methanol and acidified using 0.2 mL TFA before being purified using reverse phase preparative HPLC (eluent = TFA(aq)/MeCN). The appropriate fractions were combined and evaporated to give a residue that on trituration with ether gave a solid. The solid was dried overnight at 40 0C to give the title compound. Yield: 88 mg1H NMR (400 MHz, CD3OD) 5 8.45 (d, J= 7.2 Hz, IH), 8.11 (d, J= 3.1 Hz, IH), 8.04 (dd, J = 7.9, 3.1 Hz, IH), 7.51 - 7.43 (m, 2H), 7.36 (t, J= 1.9 Hz, IH), 7.32 (d, J= 7.7 Hz, IH), 7.18 (dt, J= 7.8, 1.9 Hz, IH), 7.13 - 7.10 (m, 2H), 6.42 (s, IH), 4.17 (s, 2H), 4.11 - 4.08 (m, IH), 3.97 - 3.91 (m, IH), 3.73 (s, 3H), 3.63 - 3.56 (m, 2H), 3.53 - 3.47 (m, 2H), 2.75 (t, J= 12.6 Hz, 2H), 2.26 (s, 3H), 1.86 - 1.77 (m, 6H), 1.74 - 1.64 (m, 2H), 1.33 (d, J= 6.7 Hz, 6H). MS: [M+H]+=670 (calc=670) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; for 2h; | Step (c) N-((ls,4s)-4-(l,5-Dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2-(2'-(morpholinomethyl)-4'-((4-propylpiperazin-l-yl)methyl)biphenyl-3- yloxy)nicotinamideA stirred solution of N-((ls,4s)-4-aminocyclohexyl)-5-fluoro-2-(2'-(morpholinomethyl)-4'- ((4-propylpiperazin-l-yl)methyl)biphenyl-3-yloxy Nicotinamide hydrochloride (174 mg, .27 mmol), 1,5 -dimethyl- lH-pyrazole-3-carboxylic acid (37.8 mg, .27 mmol) and DIPEA (0.330 mL, 1.89 mmol) in DMF (10 mL) was treated with HATU (108 mg, 0.28 mmol) and stirred for 2h. The solution was evaporated to remove most of the DMF and the residue was taken up in dichloromethane, was washed with water (3x), dried (Na2SC>4) and evaporated. The residue was purified by reversed phase preparative HPLC on a Gemini-NX column, using a gradient of methanol in 0.1% aqueous TFA solution as eluent to give a gum. The gum was taken up in a little dichloromethane and methanol and diluted with isohexane to precipitate a semi-solid. The solvents were evaporated and the residue was triturated with ether and filtered. The solid was washed with ether and dried to give the title compound as a white powder. Yield: 46 mg <n="279"/>1H NMR (400 MHz, DMSO) delta 10.32 - 10.16 (m, IH), 9.63 - 9.47 (m, IH), 8.36 (d, J= 6.9 Hz, IH), 8.26 (d, J= 3.1 Hz, IH), 8.04 - 8.00 (m, 2H), 7.65 - 7.59 (m, IH), 7.54 (t, J= 7.9 Hz, IH), 7.48 - 7.42 (m, IH), 7.38 - 7.32 (m, IH), 7.28 (d, J= 7.9 Hz, IH), 7.19 - 7.14 (m, 2H), 6.59 (s, IH), 4.45 - 4.21 (m, IH), 3.96 - 3.89 (m, IH), 3.92 (s, 3H), 3.82 - 3.42 (m, 7H), 3.25 - 2.63 (m, 7H), 2.55 - 2.35 (m, 8H), 2.14 (s, 3H), 1.84 - 1.59 (m, 10H), 0.91 (t, J= 7.4 Hz, 3H). MS: [M+H]+=767 (calc=767) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; | Step (c) N-((ls,4s)-4-(l,5-Dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2-(4'-((4-isopropylpiperazin-l-yl)methyl)-2'-(morpholinomethyl)biphenyl-3- yloxy)nicotinamideA stirred solution of N-((ls,4s)-4-aminocyclohexyl)-5-fluoro-2-(4'-((4-isopropylpiperazin-l- yl)methyl)-2'-(morpholinomethyl)biphenyl-3-yloxy Nicotinamide hydrochloride (221 mg, 0.28 mmol), 1,5 -dimethyl- lH-pyrazole-3-carboxylic acid (39.2 mg, 0.28 mmol) and DIPEA (0.342 mL, 1.96 mmol) in DMF (10 mL) was treated with HATU (112 mg, 0.29 mmol) and stirred overnight. The solution was evaporated to remove most of the DMF and the residue was taken up in dichloromethane, was washed with water (3x), dried (TN^SC^) and evaporated. The residue was purified by reversed phase preparative HPLC on a Sunfire column, using a gradient of methanol in 0.1% aqueous TFA solution as eluent to give the title compound as a white solid. Yield: 110 mg1H NMR (400 MHz, DMSO) delta 10.18 - 9.97 (m, IH), 9.44 - 9.23 (m, IH), 8.36 (d, J= 6.4 Hz, IH), 8.27 (d, J= 3.1 Hz, IH), 8.04 - 8.00 (m, 2H), 7.65 - 7.61 (m, IH), 7.54 (t, J= 7.9 Hz, IH), 7.50 - 7.45 (m, IH), 7.36 (d, J= 7.9 Hz, IH), 7.29 (d, J= 8.2 Hz, IH), 7.22 - 7.14 (m, 2H), 6.59 (s, IH), 4.36 - 3.59 (m, 20H), 3.51 - 3.38 (m, 2H), 3.21 - 2.94 (m, 4H), 2.82 - 2.64 (m, IH), 2.52 - 2.38 (m, 2H), 2.14 (s, 3H), 1.84 - 1.60 (m, 8H), 1.25 (d, J= 6.4 Hz, 3H). MS: [M+H]+=767 (calc=767) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In tetrahydrofuran; acetonitrile; at 20℃; for 2h;Product distribution / selectivity; | Step (b) N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2- (3-iodophenoxy)nicotinamide <n="115"/>To a suspension of N-((ls,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy Nicotinamide hydrochloride (1.5 g, 3.05 mmol) in acetonitrile (100 mL) was added 1,5-dimethyl-lH- pyrazole-3-carboxylic acid (1.069 g, 7.63 mmol) and triethylamine (4.25 mL, 30.50 mmol). 1- Propanephosphonic acid cyclic anhydride, 1.57M solution in THF (T3P) (5.83 mL, 9.15 mmol) was then added and the mixture stirred at RT for 2 h. The mixture was evaporated to dryness and the residue dissolved in DCM (150 mL) and washed with saturated NaHCO3 (aq), brine, dried (MgSO4) and evaporated to give a foam. The product was purified using column chromatography (eluent = neat EtOAc) to give the sub-title compound as a white foam. Yield: 1.04 g1H NMR (400 MHz, CDCl3) delta 8.36 (dd, J= 8.2, 3.1 Hz, IH), 8.07 (d, J= 3.1 Hz, IH), 7.87 (d, J= 6.7 Hz, IH), 7.64 (dt, J= 7.5, 1.5 Hz, IH), 7.55 (t, J= 1.8 Hz, IH), 7.22 - 7.14 (m, 2H), 6.69 (d, J= 7.7 Hz, IH), 6.53 (s, IH), 4.26 - 4.17 (m, IH), 4.12 - 4.03 (m, IH), 3.78 (s, 3H), 2.28 (s, 3H), 1.95 - 1.73 (m, 6H), 1.67 - 1.58 (m, 2H) MS: [M+H]+ = 578 (MultiMode+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step (e) benzyl 4-(3-(3'-(3-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3- carboxamido)cyclohexylcarbamoyl)-5-fluoropyridin-2-yloxy)biphenyl-3- yl)propyl)piperazine-l-carboxylate <n="176"/>To a solution of benzyl 4-(3-(3'-(3-((ls,4s)-4-aminocyclohexylcarbamoyl)-5-fluoropyridin-2- yloxy)biphenyl-3-yl)propyl)piperazine-l-carboxylate (0.17 g, 0.26 mmol) and 1,5-dimethyl- lH-pyrazole-3-carboxylic acid (0.036 g, 0.26 mmol) in acetonitrile (2 mL) was added triethylamine (0.356 mL, 2.55 mmol). The initial suspension was left for 10 min to become a solution. 1.57M T3P in THF (0.171 mL, 0.27 mmol) was then added and the mixture stirred for 2 h. The solution was diluted with water and extracted with EtOAc. The organics were combined, dried (MgSO4) and concentrated in vacuo to give the sub-title compound as a white fluffy foam. Yield: 0.18g MS: [M+H]+=788 (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 192-(2'-((l,4-oxazepan-4-yl)methyl)-4'-hydroxybiphenyl-3-yloxy)-N-((ls,4s)-4-(l,5- dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoronicotinamide HATU (0.083 g, 0.22 mmol) and DIPEA (0.075 niL, 0.43 mmol) were added to a solution of 1,5 -dimethyl- lH-pyrazole-3-carboxylic acid (0.030 g, 0.22 mmol) in acetonitrile (4 mL). The mixture was stirred for 10 min then a solution of 2-(2'-((l,4-oxazepan-4-yl)methyl)-4'- hydroxybiphenyl-3-yloxy)-N-((ls,4s)-4-aminocyclohexyl)-5-fluoronicotinamide (0.116 g, 0.22 mmol) in acetonitrile (4 mL) was added and the reaction stirred at RT for 2 days. The reaction mixture was diluted with EtOAc and washed with water and saturated brine. The organic was evaporated to afford crude product. The crude product was purified by preparative HPLC on a Waters X-Bridge column using a 95-5% gradient of aqueous 0.2% TFA in acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compound as a cream-coloured foam. Yield: 120 mg 1H NMR (400 MHz, DMSO) delta 9.93 (br s, IH), 9.47 (br s, IH), 8.33 (d, J= 6.9 Hz, IH), 8.25 (d, J= 3.1 Hz, IH), 8.04 (dd, J= 7.8, 2.9 Hz, IH), 7.51 (t, J= 7.9 Hz, IH), 7.24 (d, J= 7.9 Hz, 2H), 7.19 - 7.10 (m, 3H), 6.93 - 6.91 (m, IH), 6.39 (s, IH), 4.35 - 4.26 (m, 2H), 4.00 - 3.95 (m, IH), 3.85 - 3.80 (m, IH), 3.74 (s, 3H), 3.01 - 2.80 (m, 2H), 2.26 (s, 3H), 1.95 - 1.61 (m, 10H). Remaining protons obscured by solvent peak. MS: [M+H]+=657.3 (calc=657.32) (MultiMode+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 27; Syn-N-{4-[(1,5-Dimethyl-1H-pyrazole-3-carbonyl)-amino]-cyclohexyl}-2-(3- METHYLSULFANYL-PHENOXY)-NICOTINAMIDE; The amine of preparation 12 (450mg, 1. 14mmol) was taken up in a mixture of DICHLOROMETHANE and sodium hydroxide solution and the organic layer was separated and concentrated in vacuo. The residue was taken up in N, N-dimethylformamide (5mL) and the solution treated with 1-HYDROXYBENZOTRIAZOLE hydrate (154MG, 1. 14mmol), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (328mg, 1. 71 MMOL), N-ETHYIDIISOPROPYLAMINE (796PL, 4. 57MMOL) and 1, 5-DIMETHYL-1 H- PYRAZOLE-3-CARBOXYLIC acid (144mg, 1. 03MMOL) and the reaction mixture stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and 2M hydrochloric acid, the organic layer washed with 2M hydrochloric acid, saturated sodium hydrogencarbonate solution, water and brine. The organic layer was then dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with pentane: ethyl acetate 50: 50 to 30: 70 to 0: 100 to yield the title product as a glossy solid, 57mg. HNMR (CDCI3, 400MHZ) : 6 = 1.57-1. 92 (m, 8H), 2.23 (s, 3H), 2.42 (s, 3H), 3.74 (s, 3H), 4.04 (m, 1H), 4.21 (m, 1H), 6.78 (m, 1H), 6.91 (d, 1H), 7. 07 (m, 1H), 7.17 (m, 2H), 7.37 (t, 1H), 7.93 (m, 1H), 8.20 (m, 1H), 8. 60 (m, 1H) ppm. MS ES-m/z 487 [M-H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | A mixture of l-dimethyl-lH-pyrazole-S-carboxylic acid (10 g, 71.43 mmol) and SOCl2 (25.5 g, 214.29 mmol) was refluxed for 2 hr. The mixture was concentrated under vacuum. The residue was added with 200 mL of NH3-H2O dropwise with stirring at 0 C. The solids were collected by filtration, resulted in 8 g (81%) of l,5-dimethyl-lH-pyrazole-3- carboxamide as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; | 1,5 -Dimethyl- 1 H-pyrazole-3 -carboxylic acid (100 mg, 0.71 mmol) was dissolved in dry DMF (2 ml). EDC1 (205 mg, 1.1 mmol), HOBt (145 mg, 1.1 mmol) and DIPEA (0.19 ml, 141 mg, 1.1 mmol) were added at RT. The solution was stirred for 30 min. Then, 2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylamine hydrochloride (313 mg, 1.1 mmol) dissolved in the mixture of dry DMF (4 ml) and DIPEA (0.19 ml, 141 mg, 1.1 mmol) was added to the solution at RT. After stirring overnight water was added. The product was extracted into ethyl acetate. The organic phase was washed with water, dried and evaporated. The crude product was purified by flash chromatography using CH2Cl2-MeOH as a gradient eluent (100:0-95:5). Another purification was done also by flash chromatography using CH2Cl2-MeOH as a gradient eluent(100:0-99.7:0.3). The product was triturated in heptane-CH2Cl2 at RT. NMR (400 MHz, DMSO-4 : 2.26 (3H, s), 2.92 (2H, t), 3.52 (2H, m), 3.76 (3H, s), 6.31 (1H, d), 6.38 (1H, s), 7.01 (1H, d), 7.60 (1H, distorted dd), 7.64 (1H, distorted d), 7.83 (1H, d), 8.09 (lH, t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
a) Ethyl 5-(l ,5-dimethyl-lH-pyrazol-3-yl)-l ,2,4-oxadiazole-3-carboxylateEthyl aminohydroxyiminoacetate (3.78 mmol, 0.5 g), 1,5 -dimethyl- 1H- pyrazole-3-carboxylic acid (95 %, 3.78 mmol, 0.530 g) and 1,3-diisopropylcarbodi- imide (4.16 mmol, 0.525 g) were suspended in DCM (70 ml) under nitrogen atmosphere. The mixture was stirred at RT for a day. The solvent was evaporated and pyridine was added to the residue. The resulting mixture was refluxed for 6 h and stirred at RT overnight. Pyridine was evaporated and the residue diluted with DCM and water. The phases were separated and the water phase was extracted four times with DCM. The combined organics were washed with aqueous HC1 solution, saturated NaHC03, water and brine. The organic phase was dried, filtered and evaporated. The crude product was purified by flash chromatography. 0.285 g of the title compound was obtained. 1H-NMR (400 MHz, MeOH-c¾): delta 1.43 (t, 3H), 2.30 (s, 3H), 4.23 (s, 3H), 4.49 (q, 2H), 6.96 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | a) Ethyl 5-(1,5-dimethyl-1H-pyrazol-3-yl)-1,2,4-oxadiazole-3-carboxylate Ethyl aminohydroxyiminoacetate (3.78 mmol, 0.5 g), <strong>[5744-59-2]1,5-dimethyl-1H-pyrazole-3-carboxylic acid</strong> (95%, 3.78 mmol, 0.530 g) and 1,3-diisopropylcarbodiimide (4.16 mmol, 0.525 g) were suspended in DCM (70 ml) under nitrogen atmosphere. The mixture was stirred at RT for a day. The solvent was evaporated and pyridine was added to the residue. The resulting mixture was refluxed for 6 h and stirred at RT overnight. Pyridine was evaporated and the residue diluted with DCM and water. The phases were separated and the water phase was extracted four times with DCM. The combined organics were washed with aqueous HCl solution, saturated NaHCO3, water and brine. The organic phase was dried, filtered and evaporated. The crude product was purified by flash chromatography. 0.285 g of the title compound was obtained. 1H-NMR (400 MHz, MeOH-d4): delta 1.43 (t, 3H), 2.30 (s, 3H), 4.23 (s, 3H), 4.49 (q, 2H), 6.96 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 157 N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1,5-dimethyl-1H-pyrazole-3-carboxamide dihydrochloride By a method similar to Example 145, the title compound (60.0 mg) was obtained from tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate (87.2 mg) and <strong>[5744-59-2]1,5-dimethyl-1H-pyrazole-3-carboxylic acid</strong> (48.5 mg). MS (API+): [M+H]+ 325.3. 1H NMR (300 MHz, DMSO-d6) delta 0.31-0.41 (2H, m), 0.53-0.63 (2H, m), 0.98-1.11 (1H, m), 1.18-1.33 (1H, m), 1.41-1.52 (1H, m), 2.30 (3H, s), 2.37-2.47 (1H, m), 2.85-3.03 (3H, m), 3.83 (3H, s), 6.53 (1H, s), 7.12 (2H, d, J = 8.7 Hz), 7.74 (2H, d, J = 8.6 Hz), 9.11 (2H, brs), 9.89 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.021g | In methanol; acetone; | A BMes2-functionalized phenyl-triazole ligand (O.I Ommol) and [PtMe2(u-SMe2)]2 (0.032g, 0.055mmol) were added to a 20mL screw-cap vial with acetone (5mL). The resulting mixture was heated to and maintained at 75oC for 2 hours. Then, 0.1 M solution of the 1 ,5-dimethyl-1 H-pyrazole-3-carboxylic acid in methanol (2mL) was added. The resulting solution was stirred overnight. A precipitated solid was collected on a filter paper and washed with methanol, hexane and acetone (3 chi 5 mL each) and dried in air. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | Theta442] To a 4 mL scintillation vial equipped with a stir bar was charged 1,5-dimethyl-lH- pyrazole-3-carboxylic acid (23.4 mg, 0.167 rnmol), DMF (0.5 mL), HATU (66.4 mg, 0.174 mmol) and DIPEA (0.08 mL, 0.455 mmol). The mixture was stirred for 5 minutes at ambient temperature and then a solution of 3-amino-4-(4-(2,4-difluorophenoxy)piperidin-l- yljbenzonitrile (50 mg, 0.152 mmol) in DMF (0,5 mL) was added in a single portion. The reaction mixture was stirred at 70C overnight, then cooled to ambient temperature, and diluted with water (2 mL). The mixture was sonicated and stirred until a residue was observed around the inside of the vessel. The liquids were decanted, leaving an oily residue to which was added MeOH (~1 mL). The mixture was heated until it became a translucent solution and was then sonicated and stirred at ambient temperature until a precipitate was observed. The material was filtered and the solids were washed with minimal MeOH, collected, and dried under vacuum to -MS m/z [M+H]"1' 452.3. |
[ 50920-46-2 ]
1-Ethyl-5-methyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.97
[ 400755-44-4 ]
1-Ethylpyrazole-3-carboxylic Acid
Similarity: 0.89
[ 402-61-9 ]
5-Methyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.89
[ 796729-03-8 ]
5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid
Similarity: 0.89
[ 10199-57-2 ]
5-Methyl-1-phenyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.89
[ 50920-46-2 ]
1-Ethyl-5-methyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.97
[ 400755-44-4 ]
1-Ethylpyrazole-3-carboxylic Acid
Similarity: 0.89
[ 402-61-9 ]
5-Methyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.89
[ 5744-51-4 ]
Ethyl 1,5-dimethyl-1H-pyrazole-3-carboxylate
Similarity: 0.89
[ 10199-57-2 ]
5-Methyl-1-phenyl-1H-pyrazole-3-carboxylic acid
Similarity: 0.89
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :