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. : | 5370-01-4 | MDL No. : | MFCD00216024 |
Formula : | C11H18ClNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NFEIBWMZVIVJLQ-UHFFFAOYSA-N |
M.W : | 215.72 | Pubchem ID : | 21467 |
Synonyms : |
KOE-1173 hydrochloride;Mexiletine (hydrochloride);Ko 1173;Mexiletine hydrochloride
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.45 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 62.15 |
TPSA : | 35.25 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.52 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 2.95 |
Log Po/w (WLOGP) : | 2.83 |
Log Po/w (MLOGP) : | 2.4 |
Log Po/w (SILICOS-IT) : | 2.45 |
Consensus Log Po/w : | 2.13 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.16 |
Solubility : | 0.151 mg/ml ; 0.0007 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.35 |
Solubility : | 0.0958 mg/ml ; 0.000444 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.39 |
Solubility : | 0.0875 mg/ml ; 0.000406 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.09 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319 | 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 |
---|---|---|
10% | With potassium permanganate In water at 80℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In phosphate buffer |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With human liver microsomes; NADP; glucose 6-phosphate dehydrogenase In water at 37℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium tetrahydroborate at 55℃; for 72h; | 1; 2.a Example 1; Synthesis of hydroxy-N, N-diethyl mexiletine; Example 2; Conjugate of [POLVMERWITH 4-HVDROXY-N. N-DIETHVLMEXILETINE]; (a) Preparation of [N.] N-diethyl [MEXILETINE] Mexiletine monohydrochloride (0.3g, 1.4 [MMOL)] was dissolved in [ACOH] (18 mL) and the solution was heated at 55°C. Sodium borohydride (1.3g, 34 mmol) was added in small portions. The reaction was heated at [55°C] for three days then cooled and poured into ice. The pH was adjusted to 12 and the aqueous layer was extracted with DCM. Combined organic extracts were washed with brine, dried over [MGS04] and concentrated. Purification by normal phase chromatography yielded the product (0.2g, 62%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In water | Preparation of 3- (4- MEXILETINO)-L-PROPANESULFONIC acid (Compound EV) Mexiletine hydrochloride (2.45 g, 11.3 mmol) was freed with 1N NAOH (50 mL), extracted with ethyl acetate (2 x 50 mL). The combined extract was dried over sodium sulfate. The solvent was evaporated. A solution of 1,3-propane sultone (1.46 g, 11.9 mmol) in THF (35 ML) was added to the free amine. The mixture was heated at reflux for 4 hours. The mixture was cooled to room temperature; and the resultant solid material was collected by filtration, rinsed with THF (5 mL). The solid was dried overnight at 40 °C. The filtrated dried in air overnight to afford a brownish solid (1.45 g) it was less pure than the first crop thus discarded. Compound EV was obtained as a white solid (1.19 g, 56 % (99 % crude) YIELD). 1H NMR (500 MHz, DMSO) 8 1.39 (d, J= 6.3 Hz, 3H), 2.02 (T, J= 5.9 Hz, 2H), 2.26 (s, 6H), 2.67 (T, J= 5.9 Hz, 2H), 3.21 (br d, J= 19. 5 Hz, 2H), 3.61 (br s, 1H), 3.83-3. 91 (m, 2H), 6.95 (t, J= 7. 3 Hz, 1H), 7.04 (m, 2H), 8.91 (br s, 2H). 13C NMR (125 MHz, DMSO) 8 13.3, 16.0, 21.8, 44.6, 49.2, 52.9, 70.8, 124.3, 128.9, 130.4, 154.2. ES-MS 302 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium hydroxide In water; ethyl acetate | 1.A Preparation of a Compound of Formula (1) 1A. Acetyl chloride (99 ml, 1.39 mol, 1.5 eq) was added to a stirred suspension of mexiletine hydrochloride (200 g, 0.927 mol), ethyl acetate (750 ml), and 5N sodium hydroxide (750 ml) over a period of 35 minutes while keeping the temperature at ≤10° C. After the addition was complete, the reaction was allowed to stir for 45 minutes at 15-20° C. The mixture was then added to water (1 1) and the ethyl acetate layer separated. The aqueous layer was washed with ethyl acetate (2*300 ml) and the combined ethyl acetate layers were washed with saturated aqueous sodium bicarbonate until the washings were no longer acidic. The ethyl acetate solution was then washed with brine, dried over MgSO4, and concentrated to give N-[2-(2,6-dimethylphenoxy)-1-methylethyl]-acetamide (197 g, 96% yield, mp 85-85.8° C.). |
65% | With triethylamine In dichloromethane at 21℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (rac)-mexiletine hydrochloride With bromine; acetic acid at 10 - 20℃; for 14h; Stage #2: With sodium hydroxide; water at 0℃; | P6 Example P6: Preparation of 2-(2,6-dimethyl-phenoxy)-1-methyl-ethylamine (compound Z1.166) and 2-(4-bromo-2,6-dimethyl-phenoxy)-1-methyl-ethylamine (compound Z1.168):compound 21.166 compound Z1.168In a sulfonation flask 0.43g mexiletine hydrochloride (CAS5370-01-4, 2mol) is added to 10ml glacial acetic acid. The resulting solution is cooled to 100C. 0.32g bromine (2mmol) is added dropwise. The reaction mixture is stirred for 14h at ambient temperature and poured onto ice-water. The pH of the mixture is adjusted to 10 with 5M NaOH and the mixture is extracted with ethyl acetate (2x30ml). The combined ethyl acetate layers are washed with brine, dried over MgSO4, filtered and dried under reduced pressure. 0.42g of a 1 :4-mixture of 2-(2,6-dimethyl-phenoxy)-1-methyl-ethylamine (compound Zl 166) and 2-(4-bromo-2,6- dimethyl-phenoxy)-1-methyl-ethylamine (compound Z1.168) is obtained in the form of a brown oil. The mixture is used in example P2 without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium carbonate; In water; at 120 - 150℃; for 1.66667h;Microwave irradiation; | A reaction mixture of mexiletine hydrochloride (431 mg, 2.0 mmol), <strong>[854601-80-2]mPEG5-Br</strong> (2.055 g, 6.52 mmol) and potassium carbonate (1.265 g, 9.06 mmol) in water (2 mL) was placed in single-mode focused microwave reactor (CEM) and operated at 120 0C for 40 minutes, 150 0C for 20 minutes. After a period of time, more <strong>[854601-80-2]mPEG5-Br</strong> (358 mg, 1.136 mmol) was added. The mixture was irradiated using microwave conditions of 120 0C for another 40 minutes. The mixture was diluted with water (3 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent removed under reduced pressure. The residue was purified by reverse phase column chromatography to afford the desired product N,N-di-mPEG5-mexiletine 5 (973 mg) as an oil in 75% isolated yield. 1H-NMR (CDCl3): 6.98-6.85 (m, 3 H), 3.79-3.74 (m,1 H), 3.63 -3.55 (m, 28 H), 3.53-3.51 (m, 5 H), 3.47 (t, J= 6.9 H, 4 H), 3.36 (s, 6 H), 3.23-3.18 (m, 1 H), 2.78 (t, J= 6.9 H, 4 H), 2.24 (s, 6 H), 1.19 (d, J= 6.3 Hz, 2 H). LC- MS: 648.4 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With potassium carbonate In water at 120℃; for 0.5h; Microwave irradiation; | 2 A reaction mixture of mexiletine hydrochloride (225 mg, 1.043 mmol), mPEG8-Br (538 mg, 1.203 mmol) and potassium carbonate (326 mg, 2.335 mmol) in water (3 mL) was placed in single-mode focused microwave reactor (CEM) and operated at 120 0C for 30 minutes. The mixture was diluted with water (3 mL) and extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was purified by reverse phase column chromatography to afford the desired product, N-mPEG8-mexiletine (260 mg) as an oil in 46% yield. 1H-NMR (CDCl3): 6.99-6.86 (m, 3 H), 3.68 -3.60 (m, 30 H), 3.55-3.51 (m, 2 H), 3.36 (s, 3 H), 3.17-3.11 (m, 1 H), 2.95-2.84 (m, 2 H), 2.26 (s, 6 H), 1.89-1.80 (m, 2 H), 1.17 (d, J= 6.3 Hz, 2 H). LC-MS: 546.4 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃; for 22.5h; | 2 N,N-diisopropylethylamine (0.25 mL, 1.42 mmol) was added to a stirred mixture of mexiletine hydrochloride 1 (309 mg, 1.43 mmol) in 1 ,2-dichloroethane (5 mL) at room temperature. The mPEG3- propionaldehyde (461 mg, 2.09 mmol) was added and after five minutes, sodium triacetoxyborohydride (624 mg, 2.80 mmol) was added. The resulting mixture was stirred at room temperature for 22.5 hours. Sodium bicarbonate (5% aq.) was added to quench the reaction. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2 x 15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the solvent removed under reduced pressure. The residue was purified by flash column chromatography (Biotage, reverse phase column, 20-50% MeCN/water in 25 CV) to afford N-mPEG3-C3-mexiletine 3 (112 mg). 1H-NMR (CDCl3): 6.99-6.87 (m, 3 H), 3.72 -3.50 (m, 16 H), 3.35 (s, 3 H), 3.17-3.11 (m, 1 H), 2.92-2.84 (m, 1 H), 2.80-2.71 (m, 1 H), 2.26 (s, 6 H), 1.89-1.80 (m, 2 H), 1.17 (d, J= 6.3 Hz, 2 H). LC-MS: 384.3 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (rac)-mexiletine hydrochloride; 3,5-di-t-butyl-4-hydroxybenzaldehyde With triethylamine In dichloromethane at 20℃; for 23h; Heating / reflux; Molecular sieve; Stage #2: With sodium cyanoborohydride In tetrahydrofuran; methanol at 20℃; for 18h; Stage #3: With water | 1 Compound 1; Commercially available mexiletine hydrochloride (2.0 g, 9.24 mmol) was dissolved in dry dichloromethane (25 ml) containing 4A molecular sieves (2 g) and triethylamine (1.28 ml, 9.24 mmol) was added followed by commercially available 3,5-di-t-butyl- 4- hydroxybenzaldehyde (3.37 g, 13.86 mmol). The mixture was stirred at room temperature under an atmosphere of nitrogen gas for 18 hours and then refluxed for 5 hours. The reaction mixture was cooled to room temperature and filtered to remove molecular sieves. The solvent was evaporated in a rotary evaporator and the residue was dissolved in methanol (40 ml) and tetrahydrofuran (10 ml) and sodium cyanoborohydride (1.16 g, 18.48 mmol)) was added portion wise and stirring was continued over 18 hours at room temperature under a nitrogen gas atmosphere. The reaction mixture was evaporated to dryness and 100 ml of distilled water was added. This was then extracted with dichloromethane (250 ml) and then dichloromethane layer was washed with a saturated solution of sodium chloride (10 ml). The dichloromethane extract was dried over anhydrous magnesium sulfate powder and the solvent evaporated to give a thick liquid which was chromato graphed on a silica gel column and eluted with ethyl acetate/hexane (1:2) to give a light yellow liquid which solidified on storage at 4°C. Mp = 61-64 0C. Microanalysis for C26H39O2N C 78.54; H 9.89; N 3.52 (calculated), C 78.71; H 9.85; N 3.59 (obtained). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine In N,N-dimethyl-formamide | 2 N-/-butyloxycarbonyl~-glycme succinimide was coupled to (mc)-mexiletine hydrochloride in the presence of ΝMM, to yield the N-protected prodrug, (rac)-mexiletine N-£~butyIoxycarbonyl-glycine in good yield after purification by chromatography (Scheme 2).[0358] Subsequent deprotection of the BOC groups was then achieved using trifluoroacetic acid. Trituration with diethyl ether and filtration gave the required (rac)- mexiletine glycine trifluoroacetate as a white solid in excellent yield (scheme 2), Note, for the purposes of clarity, only one enantiomer of mexiletine is shown in scheme 2.CCCl NH NMM f|TCH3 H J U ft"3 «CH3 CH3 CH3 CH3 O CH3 CH3 O HO CF3 Scheme 2 - Synthetic Route for Glycne-(røc)-mexiletine trifluoroacetate[0359] Subsequent deprotection of the BOC groups was achieved using trifluoroacetic acid and filtration from diethyl ether give glycine-(røc) -mexiletine trifluoroacetate as a white solid in excellent yield.1H NMR (DMSO-d6) spectrum8.52 (d, J = 7.8 Hz, 1 H, NH), 8.03 (br, 3 H5 NH3+), 7.01 (m, 2 H, ArH), 6.93 (m, 1 H, ArH), 3.64 (m, 4 H, 2 x CH2), 2.22 (s, 6 H, 2 x CH3), 1.28 (d, J= 6.6 Hz9 3 H, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine In N,N-dimethyl-formamide | 6 The synthesis of mexiletine-(5)-glutamine amide hydrochloride was achieved in a similar manor to that for mexiletine-(S)-glutamic acid amide hydrochloride, hi this case, N- Boc-(5)~glutamine JV-hydroxysuccinimide ester was coupled to mexiletine hydrochloride to yield the N-protected prodrug, N-Boc-(S>glutamine-mexiletine in good yield.Synthetic route for raexiletine-(iS)-gIutamine amide hydrochloride [0371] Subsequent deprotection of the Boc group was achieved using 4 M hydrogen chloride in dioxane to afford mexiletine-(5)-glutamine amide hydrochloride as an off-white solid.1H NMR (DMSO-de) spectrum8.73 (d, J= 8.1 Hz, 1 H5 NH), 8.35 (br, 3 H, NH34), 7-50 (br, 1 H, 0.5 NH2), 7.01 (d, J= 7.5 Hz, 2 H5 2 x ArH), 6.92 (m, 2 H, ArH + 0.5 NH2), 4.20 (m, 1 H5 α-CH), 3.66 (m, 3 H, obscured, CH2 + CH), 2.21 (m, 6 H, 2 x CH3), 1.97 (m, 2 H, D-CH2), 1.28 (d, J= 6.6 Hz, 3 H, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; | 5 To mexiletine hydrochloride (0.75 g, 3.48 mmol) and 4-methylmorpholine (0.76 mL, 0.70 g, 6.96mmol) in dry DMF (15 mL) was added A/-Boc-(S)-methionine /V-hydroxysuccinimide ester (1.00 g, 2.89 mmol) and the solution was stirred at room temperature overnight. Ethyl acetate (75mL) was added and the solution quenched [NaCI: AcOH: H20; 0.45 g: 0.05 g: 180 mL] (150mL) with stirring for 30 minutes. The organic layer was separated and washed with 8 % aqueous sodium bicarbonate (150 mL), saturated brine (150 mL), dried (Na2S04) and concentrated. The resulting white solid of A/-Boc-(S)-methionine-mexiletine (1.10 g, 92 %) was used in the next step without further purification. |
With 4-methyl-morpholine In N,N-dimethyl-formamide | 5 The synthesis of mexiletine-[(JS)-jS'-methyl-methionme chloride] amide hydrochloride was achieved in three distinct steps. The 'activated ester' of (5>methionine, JV-Boc-(5)-methionine N-hydroxysuccinimide ester, was first coupled to mexiletine hydrochloride to yield the protected prodrug, JV~Boc-(5)-methionine-mexiIetine in good yield. Subsequent S-methylation was achieved using methyl iodide in methanol and the compound was purified by reversed-phase chromatography to give [N-Boc-(5)-Sr-methyl- methionine iodide] -mexiletine.HCI Synthetic route for mexiletine-[(S)-5-raethyl-methionine chloride] amide hydrochloride [0368] Deprotection of the Boc group was carried out using 4 M hydrogen chloride in dioxane, followed by purification by reversed-phase chromatography, to afford the desired mexiletine- [(SJ-S-methyl-methiomne] amide hydrochloride.1H NMR (DMSO-de) spoectrum9.32 (bd, 1 H5 NH)5 8.73 (br, 3 H5 NH3+), 7.02 (d, J= 7.2 Hz5 2 H5 2 x ArH), 6.92 (m, 1 H5 ArH), 4.20 (m, 1 H5 D-CH)5 4.06 (m, 1 H, CH), 3.72 (m, 4 H, CH2 + OCH2), 3.01 (s, 3H, 5-CH3), 2.98 (s, 3H, S-CH3), 2.32 (obscured, 2 H5 CH2), 2.22 (s, 6 H, 2 x CH3), 1.29 (m, 3 H, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine In N,N-dimethyl-formamide | 1 The synthesis of mexiletine-~(£)~lysine-ditrifiuoroacetate was achieved in two distinct steps. Initially, the activated ester of (£)-lysine, -V,-V-di-/-butyioxycarbonyl-(5)- lysine succinimide, was coupled to (røc)-mexiletine hydrochloride in the presence of Ν~~ methylmorpholine (NMM) to yield the N-protected prodrug, (mc)-mexiletine-Λr,N'-di-/~ butyloxycarbonyl-(tS)-Iysine, after purification by chromatography (Scheme 1).[0354] Subsequent deprotection of the BOC groups was then achieved using trifluoroacetic acid to give the desired (rαc)-mexiletine(5)-lysine~6) spectrum[0355J 8.60 (m, 1 H, NH), 8.16 (br, 3 H, NH3+), 7.76 (br, 3 H5 NH3+), 7.02 (in, 2 H, ArH), 6.92 (m, 1 H, ArH), 4.22 (m, 1 H, D-CH), 3.67 (d, J = 4.5 Hz, CH2), 2.73 (m, 2 H, NCH2), 2.21 (s, 6 H, 2 x CH3), 1.73 (m, 2 H5 CH2), 1.52 (m, 2 H, CH2), 1.30 (m, 5 H, CH3 + CH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine In N,N-dimethyl-formamide | 4 The synthesis of mexiletine~(S)-glutamic acid amide hydrochloride was achieved in two distinct steps. Initially, the 'activated ester' of (^-glutamic acid, iV-Boc-(5)-glutamic acid (fer/-butyl ester) JV-hydroxysuccinimide ester, was coupled to mexiletine hydrochloride. This gave the protected prodrug, N-Boc-(5)-glutamic acid (tert-butyl ester)~mexiletine in good yield after purification by chromatography.HCI Synthetic route for mexiletine-(5)-giutamic acid amide hydrochloride [0365] Subsequent deprotection of the Boc and tert-bntyl groups was achieved using a solution of 4M hydrogen chloride in dioxane. The crude product was purified using a Biotage Isolera automated chromatography system under reversed-phase conditions to afford the desired mexiletine-(S)-glutamic acid amide hydrochloride as a glassy white solid.1H NMR (DMSO-d6) spectrum8.71 (m, 1 H, NH), 8.31 (s, 3 H, NH34), 7.01 (d, J= 7.5 Hz, 2 H, 2 x ArH), 6.91 (m, 1 H, ArH), 4.21 (m, 1 H, glutamic acid α-CH), 3.67 (m, 3 H, obscured, mexiletine CH + OCH2), 2.36 (rn, 2 H, D-CH2), 2.23 (s, 3 H, CH3), 2.21 (s, 3 H, CH3), 1.99 (m, 2 H, CH2), 1.27 (d, J= 6.6 Hz, 3 H, CH3). | |
With 4-methyl-morpholine In N,N-dimethyl-formamide | 4 The synthesis of mexiletine-(S)-glutamic acid amide hydrochloride was achieved in two distinct steps as shown below. Initially, the 'activated ester' of (SJ-glutamic acid, A/-Boc-(S)-glutamic acid (tert- butyl ester) A/-hydroxysuccinimide ester, was coupled to mexiletine hydrochloride. This gave the protected prodrug, A/-Boc-(S)-glutamic acid (ferf-butyl ester)-mexiletine in good yield after purification by chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; | 3 To mexiletine hydrochloride (302 mg, 1.4 mmol) in anhydrous DMF (20 mL) was added N- methylmorpholine (0.33 mL, 3.0 mmol) followed by A/-Boc-(S)-homoarginine-(N02) A/-hydroxysuccinimide ester (621 mg, 1.5 mmol) and the resulting mixture was stirred at room temperature overnight. The solution was diluted with ethyl acetate (100 mL) and quenched with [NaCI: AcOH: H20; 0.45 g: 0.05 g: 180 mL] (100 mL) with stirring for 30 minutes. The organics were washed with 8 % aqueous sodium bicarbonate carbonate (100 mL), 7 % brine (100 mL), dried (MgS04) and then concentrated to give a green oil which was purified using Biotage Isolera automated chromatography system under reversed- phase conditions; acetonitrile: H20 (0.02% HCI), to give A/-Boc-(S)-homoarginine-(N02)-mexiletine (462 mg, 54 %), as a white solid. |
With 4-methyl-morpholine In N,N-dimethyl-formamide | 3 The synthesis of rnexiletine-(5)-homoarginine amide dihydrochloride was accomplished in four distinct steps. The 'activated ester' N-Boc-(5)-homoarginine-(N02) N- hydroxy succinimide ester was made via a DCC coupling between N-hydroxysuccinimide and N-Boc-(iS)-homoarginine-(Νθ2). Subsequent reaction with mexetine hydrochloride yielded the N-protected prodrug, N-Boc-(S)-homoargimne~(Νθ2)-mexiletine in good yield after purification using a Biotage Isolera automated chromatography system under reversed- phase conditions. Synthetic route for mexiletine-(5)-homoarginine amide dihydrochloride [0362] The nitro-group was reduced via catalytic hydro genation using palladium on carbon to give N-Boc-^-homoarginine-mexiletine. Removal of the Boc group was accomplished with trifluoroacetic acid. The crude product was subjected to salt exchange with 2M hydrogen chloride in diethyl ether and purified using a Biotage Isolera chromatography system under reversed-phase conditions to afford mexiletine-(S)~ homoarginine amide dihydrochloride, as a white glassy solid1U NMR (DMSO-d6) spectrum8.79 (d, J= 8.1 Hz, 1 H, NH), 835 (br> 3 H5 NH3+), 7.92 (m, 1 H, NH), 7.02 (d, J= 7.5 Hz, 2 H5 2 x ArH), 6.91 (m5 1 H, ArH), 4.20 (m, 1 H, D-CH), 3.82 - 3.65 (m, 3 H, CH + OCH2), 3.09 (m,2 H5 D-CH2), 2.22 (s, 6 H, 2 x CH3), 1.75 (m, 2 H5 CH2), 1.49 - 1.37 (m, 4 H, 2 x CH2), 1.28 (m,3 H5 CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium methylate / toluene / 12 h / Inert atmosphere 2: Chiralcel OD-H / hexane; isopropyl alcohol / 20 °C / Resolution of racemate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium methylate In toluene for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium methylate In toluene for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium methylate / toluene / 12 h / Inert atmosphere 2: Chiralcel OD-H / hexane; isopropyl alcohol / 20 °C / Resolution of racemate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium methylate In toluene for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide; tetrahydrofuran / 5 h / 20 °C 1.2: 20 °C 2.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: trifluoroacetic acid / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: 0.5 h / 20 °C 3: triethylamine / dichloromethane / 17 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: 0.5 h / 20 °C 3: triethylamine / dichloromethane / 17 h 4: 0.75 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: 0.5 h / 20 °C 3: triethylamine / dichloromethane / 17 h 4: 0.75 h / 20 °C 5: hydrogenchloride / diethyl ether / 0.33 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: N-((tert-butyloxy)carbonyl)iminodiacetic acid With dicyclohexyl-carbodiimide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 5h; Stage #2: (rac)-mexiletine hydrochloride With 4-methyl-morpholine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; | 6 To a stirred solution of A/-Boc-iminodiacetic acid (2.0 g, 8.62 mmol) in dry THF (50 mL) and dry DMF (8 mL) was added Λ/,Λ/'-dicyclohexylcarbodi-imide (1.77 g, 8.62 mmol) and the mixture was stirred at room temperature for 5 h. Mexiletine hydrochloride (1.85 g, 8.62 mmol) and 4-methylmorpholine (0.94 mL, 868 mg, 8.62 mmol) in dry DMF (15 mL) were added to the mixture and stirring was continued at room temperature overnight. The resulting suspension was filtered through Celite and the THF was removed by evaporation. Water (100 mL) was added and the solution was extracted with ethyl acetate (2 20 mL). The combined organic layers were washed with water (5 * 100 ml), saturated brine (100 mL), dried (Na2S04) and concentrated. The resulting solid was purified using a Biotage Isolera automated chromatography system under normal-phase conditions [silica column, gradient of 0→ 10 % (methanol containing 0.1 % Et3N) in dichloromethane] to give A/-Boc-mexiletine (carboxymethyl-glycine) amide (1.61 g, 48 %), as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 4-methyl-morpholine; In N,N-dimethyl-formamide; at 20℃; | To (rac)-mexiletine HCI (200 mg, 0.93 mmol) and 4-methylmorpholine (214 mu, 197 mg, 1.95 mmol) in dry DMF (5 mL) was added A/,A/'-di-f-butyloxycarbonyl-(S)-lysine succinimide (452 mg, 1.02 mmol) and the solution stirred at room temperature overnight. Ethyl acetate (50 mL) was added and the solution quenched [NaCI: AcOH: H20; 0.45 g: 0.05 g: 180 mL] (50 mL) with stirring for 30 minutes. The organics were collected and quenched (50 mL) again for a further 30 minutes. After this time, the organics were collected and washed with 8% aqueous sodium bicarbonate (50 mL), 7% brine (50mL), dried (MgS04) and concentrated. The resulting solid was chromatographed on silica gel eluting with ethyl acetate : petrol53 (4:6) to give A/,A/'-di-f-butyloxycarbonyl-(S)-lysine-(rac)-mexiletine (41 1 mg, 87%), as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 4-methyl-morpholine; In N,N-dimethyl-formamide; at 20℃; | To a stirred solution of mexiletine hydrochloride (0.50 g, 2.56 mmol) and 4-methylmorpholine (0.26 g, 0.36 mL, 2.56 mmol) in anhydrous DMF (15 mL) was added A/-Boc-(S)-aspartic acid (ferf-butyl ester) A/-hydroxysuccinimide ester (0.99 g, 2.56 mmol) and stirring was continued at room temperature overnight. Ethyl acetate (100 mL) and water (100 mL) were added and the organic layer was separated, washed with water (4 100 mL), and brine (100 mL), dried (MgS04) and concentrated to afford a gummy semi-solid solid (1 .32 g). The residue was purified using a Biotage Isolera automated chromatography system under normal phase conditions (silica column, gradient of 0? 100 % ethyl acetate in petrol) with detection at 254 nm to afford Boc-(S)-aspartic acid(ferf-butyl ester)-mexiletine (1 .03 g, 100 %), as a colourless gummy semi-solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide / 20 °C 2: methanol / 120 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; | 2 To (rac)-mexiletine hydrochloride (3.08 g, 14.24 mmol) and 4-methylmorpholine (3.3 L, 3.03 g, 29.9 mmol) in dry DMF (60 mL) was added /V-f-butyloxycarbonyl-glycine succinimide (4.27 g, 15.67 mmol) and the solution stirred at room temperature overnight. Ethyl acetate (100 mL) was added and the solution quenched [NaCI: AcOH: H20; 0.45 g: 0.05 g: 180 mL] (100 mL) with stirring for 30 minutes. The organics54 were collected and quenched (100 mL) again for a further period of 30 minutes. After this time, the organics were collected and washed with 8% aqueous sodium bicarbonate (100 mL), 7% brine (100 mL), dried (MgS04) and concentrated to give the desired A/-f-butyloxycarbonyl-glycine-(rac)-mexiletine (4.92 g, 93 %), as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 4-methyl-morpholine / N,N-dimethyl-formamide 2: hydrogenchloride / 1,4-dioxane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; | 10 To a stirred solution of mexiletine hydrochloride (2.1 1 g, 9.80 mmol) and 4-methylmorpholine (1.09 g, 1.19 ml_, 1 1.0 mmol) in anhydrous DMF (50 mL) was added A/-Boc-(S)-ornithine(Cbz) N- hydroxysuccinimide ester (5.00 g, 1 1.0 mmol) and stirring was continued at room temperature overnight. Ethyl acetate (100 mL) and water (100 mL) were added and the organic layer was separated, washed with water (5 * 100 mL), saturated brine (100 mL), dried (MgS04) and concentrated to afford afford mexiletine [A/-Boc-(S)-ornithine(Cbz)] amide (2.10 g, 41 %) as a white solid which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; | 7 To mexiletine hydrochloride (0.82 g, 3.81 mmol) and 4-methylmorpholine (0.42 mL, 0.38 g, 3.81 mmol) in dry DMF (20 mL) was added A/"-acetyl-A/£-Boc-(S)-lysine /V-hydroxysuccinimide ester (1.44 g, 3.47 mmol) and the solution was stirred at room temperature overnight. Ethyl acetate (80 mL) was added and the solution quenched [NaCI: AcOH: H20; 0.45 g: 0.05 g: 180 mL] (160 mL) with stirring for 30 minutes. The organic layer was separated and washed with 8 % aqueous sodium bicarbonate (160 mL), saturated brine (160 mL), dried (Na2S04) and concentrated. The resulting crude white solid was purified by medium-pressure chromatography on silica eluting with dichloromethane - methanol (95 : 5) to yield hf- acetyl-A -Boc-(S)-lysine-mexiletine (1.50 g, 96%), as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With Candida antarctica lipase B; palladium 10% on activated carbon; hydrogen; triethylamine In tetrahydrofuran at 50℃; for 120h; Resolution of racemate; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate In perchloric acid; water; acetonitrile at 20℃; Resolution of racemate; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 20 °C 2.2: 0.25 h / 20 °C 2.3: 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 20 °C 2.2: 0.25 h / 20 °C 2.3: 20 °C 3.1: acetic acid; palladium diacetate; lithium acetate; [bis(acetoxy)iodo]benzene; 2,6-dimethoxybenzaldehyde / 9 h / 90 °C / Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With hydrogenchloride | 4.1.2 1-(2,6-Dimethylphenoxy)propan-2-amine hydrochloride (1a·HCl) 1a was treated with gaseous HCl to obtain the corresponding hydrochloride salt (1a·HCl) as a white solid which was recrystallized from EtOH/Et2O to afford 2.9g (40%) of white crystals: mp 215-216°C; 1H NMR (500MHz, DMSO-d6): δ 1.35 (d, J=6.8Hz, 2H, CH3CH), 2.23 (s, 6H, CH3Ar), 3.50-3.58 (m, 1H, CH), 3.82 (d, J=5.4Hz, 2H, CH2), 6.91 (t, J=6.8Hz, 1H, Ar), 6.93 (t, J=7.3Hz, 1H, Ar), 7.00 (d, J=7.8Hz, 2H, Ar), 8.50 (br s, 3H, NH3+); 13C NMR (125MHz, DMSO-d6): δ 15.5 (2C), 16.4 (1C), 47.3 (1C), 72.2 (1C), 124.7 (1C), 128.9 (2C), 129.3 (2C), 130.9 (2); 154.8 (1C); Anal. (C11H18NOCl) C, H, N. |
With hydrogenchloride In ethyl acetate at 5℃; | 1 Salt formation step: 160 parts of spermine and 582 parts of ethyl acetate are put into the reaction kettle, and about 1 mol/L of ethyl hydrogen chloride solution is slowly added dropwise to a pH of about 3-5, frozen to below 5 ° C, and filtered. Drying at 60 ° C yielded 179.2 parts of mexiletine hydrochloride. | |
With hydrogenchloride | Examples: Mexiletine hydrochloride 2,6-dimethylphenol (1.2 g, 10 mmol), potassium carbonate (2.8 g, 20 mmol), acetone (20 ml) was added to a round bottom flask and stirred for 10 min. 3-bromopropyne (1.8 mg, 15 mmol) was added at room temperature and stirred at room temperature for at least 6 hours. A yellow mixture was obtained by filtration and collected. The obtained intermediate product (160 mg, 1.0 mmol), cat. [Au] (6 mg, 1 mmol%), AgOTf (2.6 mg, 1 mmol%), water (36 mg, 2 mmol) and methanol (1 mL) were sequentially added to 25 mL Kelvin tube in. After closing the reaction at 120 ° C for 6 hours, it was cooled to room temperature. Then, formic acid amine (315 mg, 5 mmol) and cat. [Rh] (6.2 mg, 1 mmol%) were added, and the reaction mixture was heated to 80 ° C in an oil bath, and after reacting for 12 hours, it was cooled to room temperature. Rotate the solvent by rotary evaporation and add a certain amount of ethyl acetate and water to extract. The product obtained in the organic phase is subjected to reflux treatment with concentrated hydrochloric acid. Rotary evaporation to remove the solvent, Finally, petroleum ether was washed and filtered to obtain a pure target compound. Yield: 87% |
With hydrogenchloride In diethyl ether; dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: ammonium acetate; sodium cyanoborohydride / methanol / 96 h / 20 °C 2: hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 20 °C 2: ammonium acetate; sodium cyanoborohydride / methanol / 96 h / 20 °C 3: hydrogenchloride | ||
Multi-step reaction with 3 steps 1: sodium bromide; tetrabutylammomium bromide; potassium carbonate / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrogen; ammonia / methanol / 100 °C / 9000.9 Torr 3: hydrogenchloride / ethyl acetate / 5 °C / pH 3 - 5 | ||
Multi-step reaction with 4 steps 1: potassium carbonate / acetone / 6 h / 20 °C 2: silver trifluoromethanesulfonate; water; [1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-2-(3H)-ylidene]gold(I)chloride / methanol / 6 h / 120 °C / Sealed tube 3: dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer / 12 h / 80 °C 4: hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | In dichloromethane at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dichloromethane / 18 h / 20 °C / pH 10.5 2: sodium hydrogencarbonate / tetrahydrofuran / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: dichloromethane / 18 h / 20 °C / pH 10.5 2: sodium hydrogencarbonate / tetrahydrofuran / 0 - 20 °C 3: potassium carbonate / methanol / 3 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: dichloromethane / 18 h / 20 °C / pH 10.5 2.1: sodium hydrogencarbonate / tetrahydrofuran / 0 - 20 °C 3.1: potassium carbonate / methanol / 3 h / 20 °C 4.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C / Schlenk technique; Inert atmosphere 4.2: 0 - 20 °C / Schlenk technique; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: dichloromethane / 18 h / 20 °C / pH 10.5 2.1: sodium hydrogencarbonate / tetrahydrofuran / 0 - 20 °C 3.1: potassium carbonate / methanol / 3 h / 20 °C 4.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C / Schlenk technique; Inert atmosphere 4.2: 0 - 20 °C / Schlenk technique; Inert atmosphere 5.1: potassium carbonate; eosin y; cyclohexa-1,4-diene / acetone / 20 °C / Sealed tube; Inert atmosphere; Irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In dichloromethane at 20℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 3-[2-(hydroxyimino)propyl]oxy}estra-1(10),2,4-trien-17-one With hydrogen In methanol at 60℃; for 4h; Autoclave; Stage #2: With hydrogenchloride In diethyl ether; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 12h; | |
10% | With 4-methyl-morpholine In N,N-dimethyl-formamide at 25℃; for 12h; | R25 Reaction R25 was performed by adding mexiletine hydrochloride (32 mg, 0.15 mmol) to a solution of 3-isocyanopropyl-1-(4-nitrophenyl)carbonate (15 mg, 0.05 mmol) and N-methylmorpholine (51 mg, 0.5 mmol) in dry DMF (0.2 mL) and the mixture was stirred at 25 °C for 12 h. The mixture was diluted with CH2CI2 (100 mL) and washed with H2O (50 mL) and brine (2x50 mL). The organic phase was dried with Mg2S04, filtered, and concentrated for purification by preparative-TLC (DCM : MeOH = 20: 1 v/v; Rf = 0.5) to afford N-(3-isocyanopropyl-1-carbamoyl)mexiletine (ICPrc-mex, Structure 21) as an off-white oil in a yield of 1.5 mg (10%). 1H NMR (400 MHz, MeOD-d4) d 7.02 (d, J= 7.4 Hz, 2H), 6.96 - 6.91 (m, 1H), 3.91 - 3.77 (m, 3H), 3.74 - 3.64 (m, 2H), 2.29 (s, 6H), 1.66-1.53 (m, 2H), 1.42 (d, J= 6.7 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: silver trifluoromethanesulfonate; water; [1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-2-(3H)-ylidene]gold(I)chloride / methanol / 6 h / 120 °C / Sealed tube 2: dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer / 12 h / 80 °C 3: hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / ethanol / 4 h / 85 - 90 °C / Schlenk technique 2: diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate / N,N-dimethyl acetamide / 16 h / 40 °C / Sealed tube; Inert atmosphere; Irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / ethanol / 4 h / 85 - 90 °C / Schlenk technique 2: diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate / N,N-dimethyl acetamide / 16 h / 40 °C / Sealed tube; Inert atmosphere; Irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 2,4,6-triphenylpyrylium tetrafluoroborate; (rac)-mexiletine hydrochloride With triethylamine In dichloromethane at 20℃; for 0.5h; Molecular sieve; Sealed tube; Stage #2: With acetic acid In dichloromethane at 20℃; Molecular sieve; Sealed tube; | |
50% | Stage #1: (rac)-mexiletine hydrochloride With triethylamine In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: 2,4,6-triphenylpyrylium tetrafluoroborate In ethanol for 4h; Reflux; | |
42% | With triethylamine In ethanol at 85 - 90℃; for 4h; Schlenk technique; |
42% | With triethylamine In ethanol at 90℃; for 5h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / ethanol / 5 h / 90 °C / Schlenk technique 2: manganese; nickel(II) bromide dimethoxyethane; 4,4'-Dimethoxy-2,2'-bipyridin / 1-methyl-pyrrolidin-2-one / 48 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0.5 h / 20 °C / Molecular sieve; Sealed tube 1.2: 20 °C / Molecular sieve; Sealed tube 2.1: bis(2,4-pentanedionate)nickel(II) hydrate; 2,6-bis(pyrazole)pyridine / N,N-dimethyl acetamide; tetrahydrofuran / 18 h / 60 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate / ethyl acetate; water 2: silver trifluoromethanesulfonate; 2-fluoropyridine; Selectfluor; cesium fluoride / chlorobenzene; dichloromethane / 24 h / 20 °C / Schlenk technique; Inert atmosphere; Glovebox |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate In water; ethyl acetate | |
With triethylamine In dichloromethane at 21℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: (rac)-mexiletine hydrochloride With trimethylamine In water Cooling with ice; Stage #2: 3,5-Dibromo-4-oxo-2,2,6,6-tetramethylpiperidine Hydrobromide In water at 50℃; for 30h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With 4,4'-Dimethoxy-2,2'-bipyridin; cesium acetate; copper diacetate In toluene at 80℃; for 24h; Schlenk technique; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 15 h / 21 °C 2: hydrogenchloride / dichloromethane; diethyl ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 15 h / 21 °C 2: hydrogenchloride / dichloromethane; diethyl ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With 1,4-diaza-bicyclo[2.2.2]octane; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; Co<SUP>III</SUP>(dimethylglyoximate)<SUB>2</SUB>(4-NMe<SUB>2</SUB>-C<SUB>5</SUB>H<SUB>4</SUB>N)Cl; acetic acid In acetonitrile at 70℃; for 36h; Inert atmosphere; Irradiation; | 1-[1-(2,6-Dimethylphenoxy)propan-2-yl]indolin-2-one (18) Following GP1 using [Ir(dtbbpy)(ppy)2]PF6 (2 mol%) as the photocatalyst,ethyl 2-(2-oxocyclohexyl)acetate (54 L, 0.3 mmol, 1.0 equiv.),and mexiletine hydrochloride (97 mg, 0.45 mmol, 1.5 equiv.) gave 18(44 mg, 50%) as a solid; Rf (hexane/EtOAc 8:2) = 0.23.1H NMR (500 MHz, CDCl3): = 7.26-7.22 (m, 2 H), 7.07 (d, 1 H, J = 7.8Hz), 7.02 (t, 1 H, J = 7.5 Hz), 6.98-6.94 (m, 2 H), 6.91-6.87 (m, 1 H),4.82 (h, 1 H, J = 7.2 Hz), 4.24 (dd, 1 H, J = 9.4, 7.5 Hz), 4.03 (dd, 1 H, J =9.4, 5.5 Hz), 3.55 (s, 2 H), 2.16 (s, 6 H), 1.62 (d, 3 H, J = 7.2 Hz).13C NMR (101 MHz, CDCl3): = 175.5, 155.3, 144.5, 130.9, 129.0,127.8, 124.8, 124.7, 124.1, 122.1, 109.8, 72.1, 48.7, 36.2, 16.2, 14.6.HRMS (ESI+): m/z [M]+ calcd for C19H21O2N: 295.1572; found:295.1563. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 2: [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; nickel(II) bromide dimethoxyethane; 4,4'-di-tert-butyl-2,2'-bipyridine / acetone / 2 h / 30 - 50 °C / Flow reactor; UV-irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; | 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester Example 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester A methylene chloride solution of 121 mg (0.27 mmol) of 6-[[(1,1-dimethylethoxy)carbonyl]amino]hexanoic acid 1-[[(4-nitrophenoxy)carbonyl]oxy]ethyl ester was added to a methylene chloride solution of 59 mg (0.27 mmol) of mexiletine hydrochloride and 71 mg (0.55 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (10% to 35% ethyl acetate/hexane) to obtain 56 mg (0.12 mmol) (44%) of the title compound. 1H-NMR (CDCl3, δ): 1.30-1.38 (2H, m), 1.39-1.51 (17H, m), 1.59-1.71 (2H, m), 2.26 (6H, s), 2.27-2.41 (2H, m), 3.10 (2H, br s), 3.67-3.75 (1H, m), 3.75-3.87 (1H, m), 4.06 (1H, br s), 4.56 (1H, br s), 5.18 (1H, br s), 6.81-6.88 (1H, m), 6.90-6.95 (1H, m), 6.98-7.02 (2H, m) |
44% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; | 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester Example 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester A methylene chloride solution of 121 mg (0.27 mmol) of 6-[[(1,1-dimethylethoxy)carbonyl]amino]hexanoic acid 1-[[(4-nitrophenoxy)carbonyl]oxy]ethyl ester was added to a methylene chloride solution of 59 mg (0.27 mmol) of mexiletine hydrochloride and 71 mg (0.55 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (10% to 35% ethyl acetate/hexane) to obtain 56 mg (0.12 mmol) (44%) of the title compound. 1H-NMR (CDCl3, δ): 1.30-1.38 (2H, m), 1.39-1.51 (17H, m), 1.59-1.71 (2H, m), 2.26 (6H, s), 2.27-2.41 (2H, m), 3.10 (2H, br s), 3.67-3.75 (1H, m), 3.75-3.87 (1H, m), 4.06 (1H, br s), 4.56 (1H, br s), 5.18 (1H, br s), 6.81-6.88 (1H, m), 6.90-6.95 (1H, m), 6.98-7.02 (2H, m) |
With N-ethyl-N,N-diisopropylamine | 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester Example 61 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid 1-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxohexyloxy]ethyl ester A methylene chloride solution of 121 mg (0.27 mmol) of 6-[[(1,1-dimethylethoxy)carbonyl]amino]hexanoic acid 1-[[(4-nitrophenoxy)carbonyl]oxy]ethyl ester was added to a methylene chloride solution of 59 mg (0.27 mmol) of mexiletine hydrochloride and 71 mg (0.55 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (10% to 35% ethyl acetate/hexane) to obtain 56 mg (0.12 mmol) (44%) of the title compound. 1H-NMR (CDCl3, δ): 1.30-1.38 (2H, m), 1.39-1.51 (17H, m), 1.59-1.71 (2H, m), 2.26 (6H, s), 2.27-2.41 (2H, m), 3.10 (2H, br s), 3.67-3.75 (1H, m), 3.75-3.87 (1H, m), 4.06 (1H, br s), 4.56 (1H, br s), 5.18 (1H, br s), 6.81-6.88 (1H, m), 6.90-6.95 (1H, m), 6.98-7.02 (2H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; | 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester Example 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester A methylene chloride solution of 175 mg (0.45 mmol) of N-[(1,1-dimethylethoxy)carbonyl]-β-alanine[[(4-nitrophenoxy)carbonyl]oxy]methyl ester was added to a methylene chloride solution of 98 mg (0.45 mmol) of mexiletine hydrochloride and 117 mg (0.91 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (10% to 50% ethyl acetate/hexane). The obtained crude product was purified again by silica gel column chromatography (10% ethyl acetate/toluene) to obtain 149 mg (0.35 mmol) (78%) of the title compound. 1H-NMR (CDCl3, δ): 1.39-1.47 (12H, m), 2.25 (6H, s), 2.59 (2H, t, J=6 Hz), 3.34-3.47 (2H, m), 3.73 (1H, dd, J=9, 4 Hz), 3.80 (1H, dd, J=9, 4 Hz), 4.02-4.18 (1H, m), 5.01 (1H, br s), 5.26 (1H, br d, J=8 Hz), 5.77 (2H, s), 6.90-6.95 (1H, m), 7.00 (2H, d, J=8 Hz) |
78% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; | 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester Example 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester A methylene chloride solution of 175 mg (0.45 mmol) of N-[(1,1-dimethylethoxy)carbonyl]-β-alanine[[(4-nitrophenoxy)carbonyl]oxy]methyl ester was added to a methylene chloride solution of 98 mg (0.45 mmol) of mexiletine hydrochloride and 117 mg (0.91 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (10% to 50% ethyl acetate/hexane). The obtained crude product was purified again by silica gel column chromatography (10% ethyl acetate/toluene) to obtain 149 mg (0.35 mmol) (78%) of the title compound. 1H-NMR (CDCl3, δ): 1.39-1.47 (12H, m), 2.25 (6H, s), 2.59 (2H, t, J=6 Hz), 3.34-3.47 (2H, m), 3.73 (1H, dd, J=9, 4 Hz), 3.80 (1H, dd, J=9, 4 Hz), 4.02-4.18 (1H, m), 5.01 (1H, br s), 5.26 (1H, br d, J=8 Hz), 5.77 (2H, s), 6.90-6.95 (1H, m), 7.00 (2H, d, J=8 Hz) |
With N-ethyl-N,N-diisopropylamine | 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester Example 64 [2-(2,6-dimethylphenoxy)-1-methylethyl]carbamic acid[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropoxy]methyl ester A methylene chloride solution of 175 mg (0.45 mmol) of N-[(1,1-dimethylethoxy)carbonyl]-β-alanine[[(4-nitrophenoxy)carbonyl]oxy]methyl ester was added to a methylene chloride solution of 98 mg (0.45 mmol) of mexiletine hydrochloride and 117 mg (0.91 mmol) of diisopropylethylamine and stirred at room temperature overnight. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (10% to 50% ethyl acetate/hexane). The obtained crude product was purified again by silica gel column chromatography (10% ethyl acetate/toluene) to obtain 149 mg (0.35 mmol) (78%) of the title compound. 1H-NMR (CDCl3, δ): 1.39-1.47 (12H, m), 2.25 (6H, s), 2.59 (2H, t, J=6 Hz), 3.34-3.47 (2H, m), 3.73 (1H, dd, J=9, 4 Hz), 3.80 (1H, dd, J=9, 4 Hz), 4.02-4.18 (1H, m), 5.01 (1H, br s), 5.26 (1H, br d, J=8 Hz), 5.77 (2H, s), 6.90-6.95 (1H, m), 7.00 (2H, d, J=8 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (R,R)-BINOL2-C/PDAN-based chiral covalent organic frameworks covered silica gel packed HPLC column In hexane; isopropanol at 25℃; Resolution of racemate; |
A870435[ 31828-71-4 ]
1-(2,6-Dimethylphenoxy)propan-2-amine
Reason: Free-salt
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 :