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Structure of DMF-DMA
CAS No.: 4637-24-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 4637-24-5 |
Formula : | C5H13NO2 |
M.W : | 119.16 |
SMILES Code : | CN(C(OC)OC)C |
MDL No. : | MFCD00008482 |
InChI Key : | ZSXGLVDWWRXATF-UHFFFAOYSA-N |
Pubchem ID : | 78373 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P210-P261-P280-P305+P351+P338 |
Class: | 3 |
UN#: | 3271 |
Packing Group: | Ⅱ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
21.7 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.23 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.6 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.53 |
Solubility | 35.5 mg/ml ; 0.298 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.25 |
Solubility | 67.7 mg/ml ; 0.568 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.24 |
Solubility | 67.8 mg/ml ; 0.569 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.86 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.41 |
* 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 |
---|---|---|
5.5% | Stage #1: With pyrrolidine In 1,4-dioxane at 100℃; for 18 h; Inert atmosphere Stage #2: at 110℃; for 4 h; |
ep 2: A mixture of 298 (3.0 g, 13.04 mmol), pyrrolidine (926 mg, 13.04 mmol), and DMF-DMA (7.76 g, 65.22 mmol) in 1,4-dioxane (20 mL) under nitrogen atmosphere was heated at 100 °C for 18 h. The reaction was concentrated under to dryness in vacuo and to the residue was added iron (3.65 g, 65.22 mmol) and HO Ac (40 mL). The resulting mixture was heated at 110 °C for 4 h, cooled to RT and filtered. The filtrate was concentrated in vacuo. The crude was purified by S1O2 chromatography eluting with petroleum ether/EtOAc (10:1) to afford 150 mg (5.5percent) of 4-bromo-5-methyl-lH-indole (300) as a yellow solid: MS (ESI) m/z = 210.1 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Stage #1: at 20℃; Heating / reflux Stage #2: With iron; acetic acid In N,N-dimethyl-formamide for 0.666667 h; Heating / reflux Stage #3: With water; sodium carbonate In dichloromethane |
Intermediate 35; 4-Bromo-6-fluoro-lH-indole; l-Bromo-5-fluoro-2-methyl-3-nitrobenzene (2.00 g, 8.55 mmol) and(dimethoxymethyl)dimethylamine (5.66 mL, 42.7 mmol) in dry DMF (20 mL) was refiuxed under N2 for 8 h, then rt. over night. The mixture was diluted with DCM and extracted 5 times with water. The organic layer was dried, filtered and concentrated under reduced pressure. The residue was dissolved in AcOH (10 mL) and added drop wise to a boiling mixture of Fe(s, fine powder) in AcOH (10 mL). The mixture was refiuxed for 40 min., partitioned between DCM and saturated aq. Na2CO3/brine (the mixture was filtered through celite before phase separation). The water layer was extracted once more with DCM. The organic layers were combined, dried and concentrated. Purification was performed by flash column chromatography (DCM/hexane 1:3) and afforded the title compound (660 mg, 39percent) as a yellow oil. MS (ESI+) for C8H5BrFN m/z 214 (M+H)+. |
27% | Stage #1: With pyrrolidine In 1,4-dioxane at 20 - 100℃; for 18 h; Stage #2: With iron; acetic acid In 1,4-dioxane for 1 h; Reflux |
Example 41 N4-(5-Cyclobutyl- 1 H-pyrazol-3-yl)-N2-((6-fluoro- 1 H-indol-4-yl)methyl)pyrimidine-2,4-diamine Formate (1-88) step 1 : To a solution of l-bromo-5-fluoro-2-methyl-3-nitrobenzene (4.69 g, 20 mmol) in 1,4-dioxane (25 mL) at RT was slowly added DMF dimethylacetal (13.3 mL) and pyrrolidine (1.7 mL). The solution was heated at 100 °C for 18 h, then concentrated in vacuo to give a dark residue. To the residue was added HOAc (30 mL) and iron powder (11 g, 200 mmol) then the mixture was heated to reflux for 1 h, cooled to RT, neutralized by addition of 50percent aq. NaOH and extracted with EtOAc (2 x 200 mL). The combined organic extracts were dried (MgSO i), filtered and concentrated in vacuo. The residue was purified by Si02 chromatography eluting with an EtO Ac/petroleum ether gradient (5 to 30percent EtOAc) to afford 1.16 g (27percent) of 4-bromo-6-fluoro-lH-indole (224) -as brown solid: MS (ESI) m/z = 213.9 [M+l] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Intermediate 35; 4-Bromo-6-fluoro-lH-indole; l-Bromo-5-fluoro-2-methyl-3-nitrobenzene (2.00 g, 8.55 mmol) and(dimethoxymethyl)dimethylamine (5.66 mL, 42.7 mmol) in dry DMF (20 mL) was refiuxed under N2 for 8 h, then rt. over night. The mixture was diluted with DCM and extracted 5 times with water. The organic layer was dried, filtered and concentrated under reduced pressure. The residue was dissolved in AcOH (10 mL) and added drop wise to a boiling mixture of Fe(s, fine powder) in AcOH (10 mL). The mixture was refiuxed for 40 min., partitioned between DCM and saturated aq. Na2CO3/brine (the mixture was filtered through celite before phase separation). The water layer was extracted once more with DCM. The organic layers were combined, dried and concentrated. Purification was performed by flash column chromatography (DCM/hexane 1:3) and afforded the title compound (660 mg, 39percent) as a yellow oil. MS (ESI+) for C8H5BrFN m/z 214 (M+H)+. | |
27% | Example 41 N4-(5-Cyclobutyl- 1 H-pyrazol-3-yl)-N2-((6-fluoro- 1 H-indol-4-yl)methyl)pyrimidine-2,4-diamine Formate (1-88) step 1 : To a solution of l-bromo-5-fluoro-2-methyl-3-nitrobenzene (4.69 g, 20 mmol) in 1,4-dioxane (25 mL) at RT was slowly added DMF dimethylacetal (13.3 mL) and pyrrolidine (1.7 mL). The solution was heated at 100 °C for 18 h, then concentrated in vacuo to give a dark residue. To the residue was added HOAc (30 mL) and iron powder (11 g, 200 mmol) then the mixture was heated to reflux for 1 h, cooled to RT, neutralized by addition of 50percent aq. NaOH and extracted with EtOAc (2 x 200 mL). The combined organic extracts were dried (MgSO i), filtered and concentrated in vacuo. The residue was purified by Si02 chromatography eluting with an EtO Ac/petroleum ether gradient (5 to 30percent EtOAc) to afford 1.16 g (27percent) of 4-bromo-6-fluoro-lH-indole (224) -as brown solid: MS (ESI) m/z = 213.9 [M+l] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridinium p-toluenesulfonate; for 1.5h;Heating / reflux; | To a solution of 2,6-dichloroacetophenone (2 g) in dry dimethylformamide dimethyl acetal (10 ml) was added pyridinium 4-toluene sulfonate (0.2 g). The mixture was stirred under nitrogen and heated to reflux for 90 minutes. An azeotrope of dimethylformamide dimethylacetal/methanol was distilled under nitrogen to complete loss of 2,6-dichloroacetophenone by thin layer chromatography. The cold mixture was evaporated to give a solid. The solid was triturated with 10percent diethyl ether in light petroleum (b.p. 40-60°C). filtered and washed with the same to give the title compound. m.p. 98-100°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | In ethanol; at 150℃; for 0.5h;Irradiation; | N'-(6-Dimethylaminomethylene-7-oxo-4,5, 6, 7-tetrahydro-benzothiazol-2-yl)-N, N-dimethyl- formamidine A mixture of 2-amino-5, 6-dihydro-4H-benzothiazol-7-one (0.5 g, 3 mmol) and N, N- dimethylformamide dimethyl acetal (1.96 mL, 1. 76 g, 14.8 mmol) in ETOH (2mL) was heated under microwave irradiation (300 W, 150 °C) for 30 min. The mixture was concentrated under vacuum before purification by flash column chromatography (50 percent EtOAc: hexane) to afford the title product as a tan solid (0.49 g, 59 percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; methylamine hydrochloride; In N-methyl-acetamide; methanol; chloroform; | EXAMPLE 1 1-methyl-5-(4-chlorophenyl)-4(1H)-pyrimidinone A 4.2 g. portion of <strong>[20101-92-2]4-chlorophenylacetamide</strong> was mixed with 6 g. of dimethylformamide dimethyl acetal in 50 ml. of dimethylformamide. The mixture was stirred at 110 C. for about 6 hours in an open flask and was then allowed to cool to room temperature. The reaction mixture was poured over ice, and the precipitated product was separated by filtration and recrystallized from benzene-hexane. The purified intermediate, p-chloro-beta-dimethylamino-N-[(dimethylamino)methylene]atropamide, m.p. 155-156 C., was obtained in a yield of 2 g. A 1.2 g. portion of the above intermediate was dissolved in 75 ml. of methanol and 3 g. of methylamine hydrochloride was added. The mixture was stirred at reflux temperature while methylamine was bubbled in. After 1 hour, the mixture was evaporated to dryness, and the residue was taken up in hot ethyl acetate, which was then evaporated to 1/5 of its volume. The product spontaneously crystallized and was separated by filtration. The solids were dissolved in 100 ml. of chloroform, 1 cc. of 1N sodium hydroxide was added, and the solution was stirred for 15 minutes and dried over sodium bicarbonate. The chloroform was evaporated under vacuum, and the product was recrystallized from hot benzene to obtain 0.6 g. of 1-methyl-5-(4-chlorophenyl)-4(1H)-pyrimidinone, m.p. 220-221 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In benzene; for 4.0h;Heating / reflux; | Intermediate 3;(2.pound.)-1-(4-bromo-2-hydroxyphenyl)-3-(dlmethylamlno)prop-2-en-1-one.; To a solution of i-(2-bromo-6-hydroxyphenyI)ethanone (35.8 g, 167 mmol) in dry benzene (800 mL) was added N.N-dimethylformamide dimethylacetal (44 mL, 333 mmol) and <n="23"/>the solution was heated to reflux for 4 h. The reaction mixture was then evaporated to dryness, dissolved in CHCI3 (300 rrL) and filtered through SiO2 (63-100 mum, 200 mL) to give after evaporation the title compound (31,9 g, 71percent) as a bright yellow solid. LC/MS data; 270.0 (M+Hf (Calculated for C11H12BrNO2 270.13). (calc. monoisotopic mass is 269.01, calc. monoisotopic mass (M+Hf = 270.01). 1H NMR data (DMSO-d6): 14.96 (s, 1H, OH), 7.93 (d, 1H, J=12.0 Hz, =CH), 7.87 (d, 1H, J = 9.0 Hz, Ar-H), 7.03 (d, 1H, J = 2.2 Hz, Ar-H)1 6,99 (dd, 1H, J1=S-O Hz7 J2=2.2 Hz, Ar-H), 5.94 (d, 1H, J=12.0 Hz, =CH), 3.21 (s, 3H, CH3), 3.00 (S, 3H1 CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In n-heptane; dichloromethane; water; N,N-dimethyl-formamide; | A. Pyrazolo[1,5-a]pyridine-4-carboxylic acid ethyl ester (777A) To a clear solution of 2-methyl-nicotinic acid ethyl ester (50.6 g, 306 mmol) in anhydrous methylene chloride (200 mL) was added O-mesitylenesulfonylhydroxylamine (73 g, 337 mmol; prepared according to a literature procedure described in Krause; J. G., Synthesis 1972, 140); in portions at 0° C. The solution obtained was stirred at 0° C. for 15 min, and then at rt for 1 h. Concentration under reduced pressure gave a yellow solid. After the solid was dissolved in anhydrous DMF (300 mL), N,N-dimethylformamide dimethyl acetal (122 mL, 918 mmol) was added at 0° C. The mixture was stirred at 0° C. for 15 min, and then at 90° C. for 3 h. The reaction mixture was concentrated under reduced pressure, mixed with H2O (200 mL), and extracted with Et2O (3*180 mL). The combined organic solutions were washed sequentially with brine (50 mL), 1N aqueous HCl (50 mL), and brine (50 mL), and dried over Na2SO4. Filtration through a SiO2 column, which was then eluted with 30percent EtOAc in heptane, gave compound 777A (43.3 g, 74percent) as a yellow solid. HPLC: 80percent at 3.20 min (retention time) plus 20percent corresponding methyl ester at 2.83 min (retention time) (YMC S5 ODS-A column 4.6*50 mm eluding with 10-90percent aqueous methanol over 4 mincontaining 0.2percent phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 191 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Example 35; This example describes the synthesis of Aldehyde 10: To a stirred solution of 9 (4.94 g, 22.3 mmol) and DMF (22.3 mL) was added DMF'DMA (8.18 g, 9.59 mL, 68.6 mmol). After heating at 135°C for 16 h, the dark red solution was cooled to 0°C and added to a rapidly stirred solution OfNaIO4 (14.7 g, 68.6 mmol) in H2O (46 mL) and DMF (23 mL) at 0°C. The reaction flask was washed with DMF (23 mL) at 0°C and added to NaIO4 mixture. The reaction was stirred at O0C for 4 h then allowed to warm to rt. After an additional 18 h, the orange solution was filtered over a pad of celite-.(R). and rinsed with EtOAc (200 mL) to remove precipitate. The filtrate was then washed with H2O (3 x 150 mL) and sat. aq. NaCl (3 x 150 mL). The dried extract (MgSO4) was concentrated in vacuo and purified by chromatography over silica gel, eluting with 40percent EtOAc / Hexanes to give the known aldehyde 10 (3.44 g, 14.8 mmol, 67percent). 1H NMR (400 MHz, CDCl3) delta 10.3 (s, IH), 8.04 (dd, J= 1.0, 8.2 Hz, IH), 7.95 (dd, J= 1.0, 8.0 Hz, IH), 7.55 (t, J= 8.0 Hz, IH); 13C NMR (100 MHz, CDCl3) delta 188.6, 148.4, 138.6, 132.9, 132.4, 123.4, 121.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | at 80℃; for 3h; | 1.3. Preparation ofl-(2-Bromo-5-fluorophenyl)-3-(dimethylamino)prop-2-en-l-one[0229] A solution of l-(2-bromo-5-fluorophenyl)ethanone (15.7 g, 72.2 mmol) in dimethylformamide dimethyl acetal (24.0 mL, 181 mmol) was heated to 8O0C for 3 h. The reaction mixture was allowed to cool to room temperature and was then cooled to about O0C. Water (100 mL) was slowly added to the reaction mixture while the internal temperature was maintained below about 2O0C. The resulting biphasic mixture was further diluted with MTBE and water. The aqueous phase was extracted with MTBE, and the combined organic phases were washed with water and brine, dried over Na2SO4, and concentrated in vacuo to give l-(2-bromo-5-fluorophenyl)-3-(dimethylamino)prop-2-en- 1-one as a dark orange solid (19.6 g, 100%). This material was used without further purification in the next reaction step. 1H-NMR (500 MHz, CDCl3) delta 7.51 (d, J = 8.8, 4.9 Hz, IH), 7.02-7.12 (m, 2H), 6.93 (dt, J = 8.2, 3.0 Hz, IH), 5.28 (d, J = 12.5 Hz, IH), 3.12 (br s, 3H), 2.89 (s, 3H). Alternatively, a standard aqueous workup was employed to isolate the title compound as a brown oil, which crystallized upon standing (250 g, 96% yield, 97% purity by HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 100℃; for 65h; | Stage A.2: N'-{6-[1-Dimethylamino-meth-(E)-ylidene]-7-oxo-4,5,6,7-tetrahydro-benzothiazol-2-yl}-N,N-dimethyl-formamidineA suspension of <strong>[17583-10-7]2-amino-5,6-dihydro-4H-benzothiazol-7-one</strong> (3.5 g, 20.81 mmol) in dimethoxymethyldimethylamine (12 mL, 90 mmol) was heated at 100° C. with stirring for 65 h. The RM was then evaporated to dryness in vacuo and the residue was suspended in EtOAc. After 1 h at 4° C., the solid was filtered off, washed with EtOAc and then dried under high vacuum at 60° C. to give the pure title product as brown crystals. LC: tR 3.25 min (method D). MS: M+H=279. 1H-NMR in DMSO-d6: 8.40 (s, 1H); 7.23 (s, 1H); 3.15 (s, 3H); 3.05 (s, 6H); 2.97 (s, 3H); 2.91 (t, 2H); 2.67 (t, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 140℃; for 16h; | General procedure: A solution of 12 (20.20 mmol) in 25 mL dimethylformamide was treated with dimethylformamide dimethyl acetal (40.40 mmol). The reaction mixture was heated at 140 ? for 16 h. After concentratedthe residue was purified by column chromatography (Pet/EtOAc 2/1) to afford desired product. (E)-3-(Dimethylamino)-1-(1-methyl-1H-indazol-3-yl)prop-2-en-1-one (13, R1 = Me). From 12 (R1 = H);1H NMR (CDCl3) delta 2.96 (3H, bs, CH3), 3.17 (3H, bs, CH3), 5.74 (1H, d,CH, J = 12.4 Hz), 7.18 (1H, t, Ind-H, J = 7.6 Hz), 7.28 (1H, t, Ind-H,J = 7.6 Hz), 7.43 (1H, d, Ind-H, J = 8.4 Hz), 7.84 (1H, d, CH,J = 12.4 Hz), 7.85 (1H, d, Ind-H, J = 8.4 Hz); HR-MS (m/z): calcd forC13H15N3O 229.1215; found 230.1230 [M + 1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | To a solution of <strong>[50607-30-2]piperidine-2,4-dione</strong> (2.00 g, 17.7 mmol) and 2-hydrazinylpyridine (1.93 g, 17.7 mmol) in water (19.7 mL) and ethanol (157 mL). The reaction was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was dried azeotropically with ethanol/toluene to give a yellow powder. Dimethylformamide (7.07 mL) was added followed by 1,1-dimethoxy-N,N-dimethylmethanamine (7.05 mL, 53.0 mmol), and the reaction was heated at 90° C. for 60 minutes. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in methanol, concentrated onto Celite®, and purified by flash column chromatography using 1-15percent methanol/dichloromethane as eluent to give Compound CE1 as a yellow solid (0.870 g, 22percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In N,N-dimethyl-formamide; at 90℃; for 4h; | To a solution of <strong>[50607-30-2]piperidine-2,4-dione</strong> (2.00 g, 17.7 mmol) in dimethylformamide (70.7 mL) was added 1,1-dimethoxy-N,N-dimethylmethanamine (2.47 mL, 18.6 mmol). The reaction was stirred at 90 C. for 4 hours, then evaporated to dryness under reduced pressure to give Compound C1 as a brown oil (3.17 g, 85%): 1H NMR (300 MHz, DMSO-d6) delta 7.94 (s, 1H), 3.24 (s, 2H), 3.13 (s, 2H), 2.87 (s, 3H), 2.71 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.8% | [1255] to a solution of ethyl 3-oxobutanoate (20.0 g, 153.7 mmol) in THF (150 ml) was added DMF-DMA (19.2 g, 161.4 mmol). The mixture was stirred at 70 C for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. To a solution of the crude product dissolving in EtOH (150 ml) was added drop-wise NH2NH2.h2o (9.2 g, 184.4 mmol). The mixture was stirred at 80c for 16 hours. The reaction mixture was concentrated under reduced pressure to remove EtOH. The residue was diluted with brine 80 ml and extracted with ethyl acetate (200 ml x 2). The combined organic layers were dried over mgs04, filtered and concentrated under reduced pressure to afford compound 257a (21.0 g, yield 87.8%) as light green solid. 1H NMR (CDCl3, 400 mhz): delta 7.96 (s, 1h), 4.29 (q, = 7.2 hz, 2h), 2.55 (s, 3h), 1.34 (t, j = 7.2 hz, 3h). MS (ESI) m/z (M+H)+ 154.8. | |
[105] 3-Methyl-1H-pyrazole-4-carboxylic acid ethyl ester was obtained by the procedure of WO2009/137338. N,N-dimethyl-formamide dimethyl acetal and ethyl acetoacetate were refluxed for 1 h followed by stirring with hydrazine hydrate in ethanol at 80C for 2 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 90℃; for 1.5h;Microwave irradiation; | A solution of <strong>[15540-81-5]1-bromo-2,5-dimethyl-4-nitrobenzene</strong> B-3a (200.0 mg, 0.869 mmol) and N,Ndimethylformamide dimethylacetal (124.3 mg, 1.043 mmol) in DMF (1.0 mL) is heated to90 00 under microwave irradiation for 30 mm. Additional N,N-dimethylformamide dimethylacetal (207.1 mg, 1.738 mmol) is added and the resulting solution heated to 90 00 under microwave irradiation for 30 mm. Again N,N-dimethylformamide dimethylacetal (207.1 mg, 1.738 mmol) is added and heated to 90 00 under microwave irradiation for 30 mm. Then the solvent is removed under reduced pressure to providecrude intermediate B-4a, which is used without further purification in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.4% | In toluene; at 20℃; for 12h; | To a solution of <strong>[50607-30-2]piperidine-2,4-dione</strong> (1.13 g, 10.0 mmol) in toluene (20 mL) was added N, N-dimethylformamide dimethyl acetal (2.24 g, 18.8 mmol) at room temperature Stir for 12 hours.The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (methanol / ethyl acetate (v / v) = 1/10) to give a yellow solid (1.30 g, 77.4percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | at 110℃; for 5h;Inert atmosphere; | General procedure: Dimethylformamide dimethylacetal (7 vol) was added under nitrogen atmosphere to corresponding substituted acetophenones (1a-c) (1g) at ambient temperature. The reaction medium was heated to 110 °C and stirred for 6?8 h. Completion of the reaction was monitored by TLC. After completion of the reaction, volatiles were removed under reduced pressure. The residue obtained was dissolved in ethyl acetate(2 vol) and hexane (8 vol) was added drop wise to it at room temperature. The resultant reaction mixture was stirred for 1h at the same temperature. The solid formed was filtered,washed with hexane and dried under vacuum. (E)-1-(2-Bromo-5-fluoro-phenyl)-3-dimethylaminopropenone(2a) This compound was prepared from 2-bromo-5-fluoro acetophenone(1a) (5g, 23.04 mmol) with dimethylformamidedimethyl acetal (35 mL). It was obtained as pale yellow solid (5.9 g, 95percent). MP: 107.8?108.6 °C. IR (ATR, cm?1) upsilon:585.78 (C-Br), 1022.41 (C-F), 1068.13 (C-O), 1164.81 (CN N), 1424.39 (C-C), 1456.96 (C-C), 1485.03 (C-C), 1547.82(C-C), 1639.92 (C=O), 3055.26 (C-H). 1H NMR (DMSOd6,300 MHz) delta (ppm): 2.84 (3H, s, ?N?CH3), 3.31 (3H, s,?N?CH3), 5.16 (1H, d, J = 12.6 Hz, =C?H?CO), 7.15?7.17(2H, m, Ar?H), 7.21 (1H, d, J = 13.0 Hz, =CH?N?(CH3)2), 7.64 (1H, dt, J1 = 13.8 Hz, J2 = 5.1 Hz, Ar?H). 13C NMR(DMSO-d6, 100MHz) delta (ppm): 37.48 (?N?CH3), 45.01(?N?CH3), 95.1 (?ene?CH), 113.79 & 113.86 (d, 3J C?F =7.8 Hz , ArC?Br), 115.84 & 116.07 (d, 2J C-F = 23.2 Hz,Ar-C), 117.43 & 117.66 (d, 2J C?F = 22.4 Hz, Ar?C),134.99 & 135.07 (d, 3J C-F = 8 Hz, Ar?C), 146.6 (Ar?C),154.8 (?ene?CH), 160.35 & 162.80 (d, 1J C-F = 244.8 Hz,ArC?F), 187.8 (?C=O). LC-MS (ESI, m/z): 274.42[M+2 H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; at 110℃; for 2h; | Step 1 - 4-((Dimethylamino)methylene)<strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (0554) [00355] To a solution of 1,1-dimethoxy-N,N-dimethylmethanamine (48.4 g, 407 mmol) in dioxane (150 mL) was added <strong>[22929-52-8]tetrahydrofuran-3-one</strong> (7.00 g, 81.3 mmol). The reaction mixture was stirred at 110 °C for 2 hrs. On completion, the mixture was concentrated in vacuo. The residue was triturated with petroleum ether to give the title compound. 1H NMR (400 MHz, DMSO-d6) delta = 7.15 (s, 1H), 5.00 (s, 2H), 3.86 (s, 2H), 3.01 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Add ?v?N-dimethyiamide dirnethylacetal (60 1iL) to a solution of N-(2-amino-1-methyl-2-oxoethyl)-3-chloro-N-(cyclopropylmethyl)-5-(trifluoromethoxy)benzamide (106 mg) in CH2CI2 (5 mL) and stir at reflux for 1 h. Cool to rt., concentrate underreduced pressure, dissolve the residue in 1,4-dioxane/AcOFI (1.5 mL/1.5 mL). add 2-hvdrazinopyrimidine (48 mc) and stir at 90 C for 1 h. Cool to rt., concentrate underreduced pressure, partition the residue between NaHCO3 (aq. sat.) and CH2CI2. Separate the layers. extract the aqueous phase three times with Cl-12C12, dry the combined organic extracts over Na2SO4, filter, concentrate under reduced pressure and purif? the residue by chromatography to provide 3-chioro-If-(cyciopropyImetiwi)N-[1 -(2-pyrimidin-2-yi-1 ,2.4-triazoi-3-yl)ethyi -5-(trifiuoromethoxy)benzamide (101 mg, 59%). LCMS (method2): Rt 1.64 min. m/ (ES+) 467 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Add N.N-dimeth lamide dimethylacetal (32 iL) to a solution of N-[(1S)2-amino-1 -methyl-2-oxo-ethyiI-Nprop-2-ynyi-3,5-bis( rifluoromethyi)henzamide (58 mg) in CH2CI2 (0.7 mL) and stir at refiux for 1 h. Cool to r.t., concentrate under reduced pressure, dissolve the residue in 1,4dioxane/AcOH (0.7 mL/0.7 rnL), add 2- hydrazinopyrirnidine (23 rng) and stir at 50 C overnight. Cool to r.t., concentrate underreduced pressure, partition the residue between NaHCO3 (aq. sat.) and EtOAc, Separate the layers, diy the organic phase over MgSO4, filter, concentrate under reduced pressure arid purifz the residue by chromatography to provide -prop-2-ynyl-N-[(1)-1-(2- pyrimidin-2-yi-1 ,2,4-triazol-3-yl)ethyiI-3,5-bis( rifluoromethyi)henzamide (38 mg, 58%). LCMS: (method 4) Rt 1.59 mm, m/z (ES) 469 [M+H]. Chiral HPLC: column ChiraipakAD-H (250x4.6 mm), heptanefiPrOH/diethylamine 95:5:0.1, flow rate I mL/min, r.t., lambda 240nm , Rt 14.1 min, ee>99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Add N,N-dirnethvlarnide dimethviacetal (25.5 rnL) to a solution of N-[(15)-2- amino- I -rnethyl-2-oxo-ethvl] -N-(cyclopropyirnethyl)-3, 5-bis(trifluorornethyl)benzarnide (48.7 g) in CH?C12 (490 mL) and stir at refiux for 1 h 15 mm. Cool to r.t., concentrate under reduced pressure, dissolve the residue in 1,4-dioxane/AcOFI (275 mL/275 mL). add 2-hydrazinopyrimidine (16.9 g) and stir at 50 C overnight. Cool to r.t., concentrate underreduced pressure, and partition the residue between water and EtOAc. Filter through Celite, separate the layers, wash the organic phase with Na}-1C03 (aq. sat.), diy the organic phase over MgSO4, concentrate under reduced pressure and purify the residue by chromatography and precipitation fiorn diethyl ether and petroleum ether to provide N(cycIopropy1rnethyl)j(1 )-1-(2-pyrirnidin-2-y1-1 ,2,4-triazol-3-yl)ethyl -3,5-his(trifiuoromethvl)benzamide (29.7 g. 48%). LCMS: (method 4) Rt 1.79 mm, rn/z (ES)=485 [M-1-H]. Chiral HPLC: column Chiraipak AD-H (250x4.6 mm), heptane/1PrOH/diethylarnine 95:5:0.1, flow rate 1.3 mL/min, T = 30 C, 2 240 nm, Rt 13.5 mm. (R1 for R-enantiomer 16.9 min ee >99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | Add NN-dimethylarnide dimethylacetal (38 pt) to a solution of N-[(15-2-amino-1 -methyl-2-oxo-ethyl -N-(inethyl)-3,5-bis(trifiuoroinethyl)benzarnide (90% w. purity,mg) in CH2CI2 (2 mL) and stir at reflux for 1.5 h. Cool to r.t., concentrate under reduced pressure, dissolve the residue in 1,4-dioxane/AcOH (0.5 mL/0.5 mL), add 2- hydrazinopyrirnidine (25 rng) and stir at 50 C overnight. Cool to r.t., concentrate under reduced pressure, and partition the residue between water and EtOAc. Filter throughCelite?, separate the layers, wash the organic phase with NaCi (aq. sat), dry the organic phase over MgSO4, concentrate under reduced pressure and purifi the residue by chromatography to provide N-methvl-AT-[( I 5- I -(2-pyrimidin-2-yi- I ,2,4-triazol -3- yi)ethyi] -3,5-bis(trifluoromethyi)benzamide (41 mg, 49%). LCMS: (method 4) Rti.5 0 mm. m/z (ES+)=445 [M-l-H]. Chiral HPLC: column Diacel Chiraipak IC-3 (150x4.6 mm), 0.1% TFA in H20/0. 1% TFA in MeCN 48:52, flow rate 0.3 mL/min, T 25 C, 2235 nm. Rt 16.4 mm (Rt for R-enantiomer 15.4 mm), ee 99.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | Add iV,NdirnethyIamide dimethylacetal (220 tL) to a solution of iV-(2-amino-1- inethyl-2-oxo-ethyi)-N-(cyclopropyimethyl)-3,5-bis(tiifiuoromethyl)benzamide (408 rng)in CH2CI2 (5 mL) and stir at reflux for 1.5 h. Cool to rt., concentrate under reduced pressure, dissolve the residue in I ,4-dioxane/AcOH (6 rnL/0. 6 mL), add 2- hydrazinopyrirnidine (183 rng) and stir at 50 C overnight. Cool to r.t., concentrate under reduced pressure, partition the residue between Nal-ICOs (aq. sat.) and EtOAc. Separate the layers. dry the organic phase over MgSO4, concentrate under reduced pressure andpurify the residue by chromatography to provide N-(Cyciopropyimethyl)-N-[ 1 -(2- pyrimidin-2-yi- 1 ,2,4-triazol-3-yl)ethyi] -3,5-bis(trifluoromethyi)benzamide (173 mg, 33%). LCMS (method 5): Rt 2, 16 min m/z (ES+) 485 [M+H]+. Chiral HPLC: column Chiraipak AD-H (250x4.6 mm), heptane/IPrOH/diethylamine 95:5:0.1, flow rate 1.3 rnL/min, T = 30 C, 2 240 nrn, Rt 13.5 and 16.9 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Add N,N-dimethylamide dimethylacetal (3.3 ml.) to a solution of 2- brompropanamide (2.5 g) in CH2CI2 (30 ml,) and stir at reflux for 1.5 h. Cool to r.t, concentrate under reduced pressure, dissolve the residue in 1,4-dioxane/AcOH (15 mL/15 mL), add 2-hydrazinopyrimidine (2.2 g) and stir at 50 C overnight. Cool to r.t., concentrate under reduced pressure and partition the residue between water and EtOAc. Separate the layers, wash the organic phase with NaHCC (aq. sat.), dry the organic phase over MgS04, filter, concentrate under reduced pressure and purify the residue by chromatography to provide 2-[5-(l -bromoethyl)-l ,2,4-triazol-l-yl]pyrimidine (2.0 g, 48%), LCMS (method 4): R, 0,55 min, m/z (ES+) = 254 [M(79Br)+H]+ and 256 [M(81Br)+H]4. | |
A 250 mL flask was charged with 2-bromopropanamide (2.8 g, 18 mmol), dichloromethane (54 mL), and 1,1-dimethoxy-N,N-dimethyl-methanamine (3.2 g, 27 mmol). The suspension was refluxed for one hour, and the resulting colorless solution was evaporated. The residue was transferred in a 100 mL flask and dissolved in 1,4-dioxane (18 mL) and acetic acid (16 mL). Pyrimidin-2-ylhydrazine (2 g, 18 mmol) was then added and the white suspension stirred at 90C for two hours. The resulting homogeneous mixture was evaporated and quenched with a saturated aqueous solution of sodium hydrogen carbonate (30 mL). The aqueous phase was extracted with ethyl acetate (2 × 10 mL) and the combined organic phases were washed with water (2 × 5 mL), brine (5 mL), dried with Na2SO4, filtered and evaporated to give a crude orange oil. Purification by chromatography over silica gel (cyclohexane/ethyl acetate gradient, 100:5 to 0:100) afforded 2-[5-(1-bromoethyl)-1,2,4-triazol-1- yl]pyrimidine as a white solid. (0519) 1H-NMR (400 MHz, CDCl3, ppm): d = 8.90 (d, J=4.8 Hz, 2H), 8.07 (s, 1H), 7.40 (t, J=4.8 Hz, 1H), 6.41 (q, J=6.9 Hz, 1H), 2.24 (d, J=6.9 Hz, 3H); (0520) LC-MS (method 1): Rt 0.64, m/z = 255/256 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Add NJV-dimethylamide dimethylacetal (2.8 mL) to a solution ofN-(2-amino-I- methyi-2-oxo-ethvi)-N-prop-2-vnyi-3,5-bis(trifluorornethyi)benzarnide (5 0(1 g) in CH2C12 (70 mL) and stir at reflux for 2 h. Cool to r.t., concentrate under reduced pressure, dissolve the residue in 1,4-dioxane/AcOH (80 rnL/8 rnL), add 2-hydrazinopyrirnidine (2.48 g) and stir at 50 O( overnight. Cool to r.t., concentrate under reduced pressure,partition the residue between NaHCO3 (aq. sat.) and EtOAc. Separate the layers, extract the aqueous phase three times with EtOAc, dry the combined organic extracts over MgSO4, filter, concentrate under reduced pressure and purify the residue by chromatography to provide N-prop-2-ynyi-W[i-(2-pyrimidin-2-yi-i ,2,4-triazoi-3- yi)ethyij-3.5-bis(irifluorornethyi)benzarnide (297 g, 46%). LCMS (method 2): R 1.52mm, m/z (ES+) == 469 [M+H]+. Chiral HPLC: column Chiralpak AD-Fl (250x4.6 mm), heptane/IPrOH/diethvlamine 95:5:0.1, flow rate 1 mL/min. it., . 240 nrn. Rt 13.8 and 16.6 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2-Chloro-5-nitrobenzenesulfonamide (674 mg, 2.85 mmol) and 1 -cyclopropyl-4-(4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 /-/-pyrazole (1 .00 g, 4.27 mmol) were dissolved in n- propanol (34 ml) and bis(triphenylphosphine)palladium(ll) dichloride (CAS 13965-03-2) (100 mg, 142 muetaetaomicronIota) and triphenylphosphine (37.3 mg, 142 muetaetaomicronIota) were added. The reaction was purged with argon for 5 minutes and aq. potassium carbonate (5.7 ml, 1.0 M, 5.7 mmol) was added. The reaction was heated at 100°C for 3h. Afterwards the mixture was filtered over Celite and the solvent was removed under reduced pressure. Ethyl acetate and water were added. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over Whatmanfilter and the solvent was removed under reduced pressure. The crude was used in the next step without further purification. (0458) 2-(1 -Cyclopropyl-1 /-/-pyrazol-4-yl)-5-nitrobenzenesulfonamide (1.17 g, 3.79 mmol) and 1 ,1 -dimethoxy-/V,/V-dimethylmethanamine (1 .0 ml, 7.6 mmol) were dissolved in DMF (25 ml) and the reaction was stirred at room temperature until completion of the reaction. The solvent was removed under reduced pressure and the crude was used without further purification in the next step. (0459) 2-(1 -Cyclopropyl-1 /-/-pyrazol-4-yl)-/V-[(dimethylamino)methylidene]-5- nitrobenzenesulfonamide (1.84 g, 5.06 mmol) was dissolved in THF (30 ml) and the flask was flushed with nitrogen. Palladium on charcoal (10percent loading, 53.9 g, 506 muetaetaomicronIota) was added and the flask was evacuated and subsequently flushed with hydrogen (1 bar). Stirring was continued at room temperature until completion of the reaction. The reaction mixture was filtered over Celite and the solvent was removed under reduced pressure. The crude was used without further purification in the next step (1.3 g, 53percent purity, 75percent yield over 3 steps). (0460) LC-MS (Method A): Rt = 0.70 min; MS (ESIpos): m/z = 334 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.3 g | 1.1 g (81.6 % purity, 2.53 mmol) ofN-[(2S)-l-aminoamino-l -oxopropan-2-yl]-3-chloro-5- [(trifluoromethyl)sulfonyl]benzamide were dissolved in 20 mL dichloromethane. 447 mg (3.75 mmol) N. N- d i m c t h y 1 fo r m a m i d c dimethyl acetal were added, and the reaction mixture was refluxed for 90 minutes. The solvents were removed under reduced pressure, and the remaining residue was dissolved in a mixture of 20 mL dioxane and 3 mL acetic acid. 336 mg (3.05 mmol) 2-hydrazinopyrimidine were added. The reaction mixture was stirred over night at 50 C, concentrated in vacuo and diluted with water and ethyl acetate. The separated organic phase was washed with aqueous sodium bicarbonate, dried over anhydrous Na2SO i, filtered and concentrated in vacuo. The remaining residue was purified by pHPLC to obtain 0.3 g 3-chloro-N- {(l S)-l-[l-(pyrimidin-2-yl)-lH-l,2,4-triazol-5-yl]ethyl} -5- [(trifluoromethyl)sulfonyl]benzamide as a colorless solid. -NMR (400 MHz, d6-DMSO): see NMR peak list in table 1. ES1 mass [m/z]: 460.9 [M+H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.51 g | To a solution of 4.78 g (25.3 mmol) N2-(tert-butoxycarbonyl)-L-alaninamide in 100 mL CH2CI2 was added 4.97 mL (37.5 mmol) N,N-dimethylformamide dimethylacetal. The solution was heated at reflux for 2 h after which the solvent was removed in vacuuo. The residue was dissolved in a mixture of 45 mL l,4-dioxane and 45 mL glacial acetic acid. 3.41 g (31 mmol) 2-hydrazinopyrimidine were added and the mixture stirred at 50 C for 45 min. The solvents were removed under reduced pressure, a saturated aqueous solution of NaHCC was added and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were dried with Na2S04 and the solvent was removed under reduced pressure. The residue was purified by reversed phase chromatography (H2O / acetonitrile) to provide 4.51 g of tert-butyl {(lS)-l-[l-(pyrimidin-2-yl)-lH-l,2,4-triazol-5-yl]ethyl}carbamate. Mi> = +82 (c = 0.95; ethanol) ?H NMR (DMSO-de, 400 MHz): NMR peaklist: d= 9.0011 (3.9); 8.9890 (3.9); 8.1196 (2.5); 7.6599 (2.2); 7.6477 (4.2); 7.6356 (2.1); 7.4658 (0.7); 7.4465 (0.7); 5.5270 (0.5); 5.5091 (0.7); 5.4910 (0.5); 3.3264 (15.3); 2.5262 (0.3); 2.5214 (0.6); 2.5127 (8.5); 2.5083 (17.6); 2.5037 (23.5); 2.4992 (17.0); 2.4948 (8.1); 2.0759 (10.4); 1.4486 (3.8); 1.4312 (3.5); 1.2827 (16.0); 1.0275 (0.9); -0.0002 (7.8). (0709) ESl mass [m/z]: 235.2 [M-CLLL+H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35.2% | 304 mg (1.02 mmol) of N-[(2S)-l-amino-l-oxopropan-2-yl]-3-chloro-5-(N- methoxyethanimidoyl)benzamide and 182 mg (1.53 mmol) N,N-dimethylformamide dimethyl acetal were dissolved in 20 mL dichloromethane and refluxed for 2 h. The solvents were removed under reduced pressure, the remaining residue was taken up with a mixture of 10 mL dioxane and 1 mL HOAc. 137 mg (1.24 mmol) of 2-hydrazinopyrimidine were added and the reaction mixture was stirred at 50 C over night. After evaporation of the solvents under reduced pressure, the residue was dissolved in dichloromethane, washed with an aqueous saturated NaHCCb solution, and the separated organic phase was reduced in vacuao again. Purification by reversed phase chromatography (LbO / acetonitrile) provided 148 mg (yield: 35.2 %) of the title compound as an off-white solid. -NMR (400 MHz, de-DMSO): see NMR peaklist in table 1. ES1 mass [m/z]: 400.2 [M+H] |
Tags: 4637-24-5 synthesis path| 4637-24-5 SDS| 4637-24-5 COA| 4637-24-5 purity| 4637-24-5 application| 4637-24-5 NMR| 4637-24-5 COA| 4637-24-5 structure
A1638647 [61853-18-7]
1,1-Dimethoxy-N,N-dimethylmethanamine-13C
Reason: Stable Isotope
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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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