There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
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. : | 108499-32-7 | MDL No. : | MFCD09834150 |
Formula : | C7H7BrO2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GFOPHLFSDVVYGB-UHFFFAOYSA-N |
M.W : | 235.10 | Pubchem ID : | 11424851 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.29 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 48.43 |
TPSA : | 54.54 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.04 cm/s |
Log Po/w (iLOGP) : | 2.37 |
Log Po/w (XLOGP3) : | 2.38 |
Log Po/w (WLOGP) : | 2.28 |
Log Po/w (MLOGP) : | 1.75 |
Log Po/w (SILICOS-IT) : | 3.36 |
Consensus Log Po/w : | 2.43 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.94 |
Solubility : | 0.273 mg/ml ; 0.00116 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.17 |
Solubility : | 0.16 mg/ml ; 0.000682 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.01 |
Solubility : | 0.231 mg/ml ; 0.000984 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.7 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501 | UN#: | 3265 |
Hazard Statements: | H302-H314 | Packing Group: | Ⅱ |
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 |
---|---|---|
70% | With 4-methylmorpholine N-oxide In acetonitrile at 25℃; for 12 h; Molecular sieve | To a solution of 4-methylmorpholine N-oxide (0.449 g, 3.83 mmol) in MeCN (5 mL) at 0 °C, in presence of molecular sieves 3Å, compound 13 in MeCN (0.300 g, 1.28 mmol) was added. Reaction mixture was kept stirring at 25 °C for 12 h and then filtered and purified by column chromatography on silica gel (EtOAc/n-hexane 1:20) to obtain the title compound (yield 70percent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1H-imidazole; bromine; triphenylphosphine; In dichloromethane; at 20℃; for 0.166667h; | Bromine (0.47 mL, 9.12 mmol) was added to a solution of imidazole (617 mg, 9.06 mmol) and triphenylphosphine (2.40 g, 9.15 mmol) in CH2Cl2 (30 mL) at room temperature. A solution of methyl 5-hydroxymethyl-thiophene-2-carboxylate (prepared according to the procedures described in WO2004/037808; 1.30 g, 7.59 mmol) in CH2Cl2 (10 mL) was then added. After 10 min at room temperature, the reaction mixture was concentrated in vacuo. Purification of the crude residue by flash column chromatography on 80 g of silica gel (hexane?EtOAc, gradient) afforded 1.70 g (95%) of the title compound (B). |
95% | With 1H-imidazole; bromine; triphenylphosphine; In dichloromethane; at 20℃; for 0.166667h; | Preparation 1; Methyl 5-bromomethyl-thiophene-2-carboxylate (B); Bromine (0.47 mL, 9.12 mmol) was added to a solution of imidazole (617 mg, 9.06 mmol) and triphenylphosphine (2.40 g, 9.15 mmol) in CH2Cl2 (30 mL) at room temperature. A solution of methyl 5-hydroxymethyl-thiophene-2-carboxylate (prepared according to the procedures described in WO2004/037808; 1.30 g, 7.59 mmol) in CH2Cl2 (10 mL) was then added. After 10 min at room temperature, the reaction mixture was concentrated in vacuo. Purification of the crude residue by flash column chromatography on 80 g of silica gel (hexane ?EtOAc, gradient) afforded 1.70 g (95%) of the title compound (B). |
84% | With 1H-imidazole; bromine; triphenylphosphine; In dichloromethane; at 20℃; for 4h; | To a flask charged with dry dichloromethane (50 mL) was added in order triphenyl phosphine (228 mg, 0.87 mmol), imidazole (59.3 mg, 0.87 mmol) and bromine (44.6muL, 0.87 mmol). The reaction mixture was then treated with a solution of 1 (100 mg, 0.58 mmol, in <n="38"/>dichloromethane (5 niL)), dropwise and stirred at room temperature under nitrogen for 4 h. When the reaction was deemed complete the mixture was concentrated to dryness under reduced pressure and subjected to flash chromatography (20%ethyl acetate/petrol) to afford the desired 5-bromomethyl-thiophene-2-carboxylic acid methyl ester (m) as colourless crystals, (115 mg, 84%).1H NMR (300 MHz, CDCl3) delta 3.89 (3H, s, CH3), 4.67 (2H, s, CH2), 7.10 (IH, m, thienylH), 7.64 (IH, d, /=3.6Hz, thienylH).HPLCmethod2 92%/1.14 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Sodium hydride (60% oil dispersion, 26 mg, 0.65 mmol) was added to a solution of alcohol 2 (180 mg, 0.44 mmol) in DMF (1.1 mL) at 0 C. After 5 min, the reaction was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to a -40 C. and a solution of bromide B (Preparation 1, 125 mg, 0.53 mmol) in DMF (1.1 mL) was added via cannula. After 3 h at -40 C., the reaction was quenched with 1 N HCl (10 mL) and extracted with EtOAc (3×30 mL). The combined extracts were washed with H2O (2×15 mL) and brine (20 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 12 g of silica gel (hexane?EtOAc, gradient) afforded 97 mg (39%) of desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5-Bromomethyl-2-carbomethoxythiophene (III-3). This compound was prepared from 5-methylthiophene-2-carboxylic acid by the method of Gogte et al, Tetrahedron, 23, 2443-51 (1967). | ||
Synthesis Example 14-1: Synthesis of 2-bromomethyl-5-methoxy carbonylthiophene (Compound IV-4) 2.05 g of commercially available 5-methylthiophene carboxylic acid was dissolved in 60 ml of methanol, and then a hydrochloric acid gas was brown into the solution for 5 minutes. After 23 hours, the reaction solution was concentrated, and then a 1 mol/l sodium hydroxide aqueous solution was added thereto, followedbyextractionwithchloroform. An organic layer was washed with a saturated salt solution and was then dried with anhydrous sodium sulfate and concentrated. 500 mg of the resulting residue was dissolved in 10 ml of carbon tetrachloride, followed by the addition of 570 mg of N-bromosuccinimide and 53 mg of azobisisobutyronitrile. After the resultant solution was stirred in oil bath for 20 hours at 70C, the reaction solution was filtrated, and then the filtrate thereof was then concentrated. The resulting residue was purified by means of silica gel column chromatography (15 g, hexane/ethyl acetate = 8/1). Consequently, 516.1 mg of the above-mentioned compound was obtained as light-yellow syrup. MS(EI,Pos.):m/z=233,235[M+1]+ 1H-NMR(500MHz,CDCl3):delta=3.89(3H,s),4.68(2H,s),7.10(1H,d,J=3.7Hz),7.64(1H,d,J=3.7Hz). | ||
With N-Bromosuccinimide; dibenzoyl peroxide; In methanol; tetrachloromethane; methyl 5-methylthiophene-2-carboxylate; | (ii) 5-bromomethyl-2-carbomethoxythiophene A solution of 5-methyl-2-thiophene carboxylic acid (25 g, 0.176 mol) in 500 ml of methanol was saturated with gaseous hydrochloric acid at 0 C. The reaction mixture was stirred at room temperature for 18 hours and then refluxed for 48 hours. The solvent was removed in vacuo and the crude methyl 5-methyl-2-thiophene carboxylate was used without further purification. The methyl ester prepared above (11.07 g, 0.071 mol) was dissolved in 200 ml of carbon tetrachloride under argon. N-bromosuccinimide (13.25 g, 0.074 mol) and dibenzoyl peroxide were then added. The reaction mixture was refluxed for 2 hours and allowed to stand at room temperature for 18 hours. The solids were collected and the filtrate was concentrated in vacuo to give 19 g of 5-bromomethyl-2-carbomethoxythiophene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In dichloromethane; water; for 0.666667h; | To a solution of 500mg (2. 13MMOL) 5-BROMOMETHYL-THIOPHENE-2-CARBOXYLIC acid methyl ester and 381mg (2.13mmol) 2,3-dihydro-benzo [1, 4] dioxine-6- carbaldehyde oxime in 2ML dichloromethane were added 2. 0ml 2.2M aqueous sodium hydroxide solution and 902mg (2.55mmol) tertrabutylammonium hydrogen sulfate while vigorously stirring. After 10 minutes another 2. 0ML 2.2M aqueous sodium hydroxide solution and 902mg (2. 55MMOL) tertrabutylammonium hydrogen sulfate were added. This procedure was repeated one more time. After 20 minutes 8ml saturated aqueous bicarbonate solution was added. The aqueous phase was extracted three times with ethyl acetate and the combined organic phases were washed with brine and dried over NA2SO4. The solvent was evaporated and the residue was subjected to silica gel chromatography (hexane/ethyl acetate 4: 1, then 3: 1) to yield 214mg (0. 64MMOL) 5- (2, 3-Dihydro-benzo [1, 4] dioxin-6- ylmethyleneaminooxymethyl) -thiophene-2-carboxylic acid methyl ester; exact MW [M+H] calc'd: 334.07 ; MW found [M+H]: 334.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Methyl 5-bromomethylthiophene-2-carboxylate may be prepared according to Curtin M. L., Davidsen S. K., Heyman H. R., Garland R. B., Sheppard G. S., J. Med. Chem., 1998, 41 (1), 74-95. | ||
This compound is shown in Table 1 as compound 3. Preparation of thiophene analogues of 10deazaaminopterins is illustrated in Reaction Scheme 3. Starting compounds III-1 and III-2, namely 5-methylthiophene-2-carboxylic acid and methyl 5-methylthiophene-2-carboxylate, are commercially available from Sigma, St Louis, Mo. 5-Bromomethyl-2-carbomethoxythiophene (III-3) is prepared from 5-methylthiophene-2-carboxylic acid by the method described in Tetrahedron, 23:2443-51 (1967). A mixture of III-3, sodium cyanide, benzyltrimethylammonium chloride, dichloromethane, and water is stirred rapidly for about 16 hours. | ||
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; | General procedure: Preparation Example 62 To a mixture of 5.27 g of benzyl 5-methylthiophene-2-carboxylate and 100 mL of carbon tetrachloride were added 4.18 g of N-bromosuccinimide (NBS) and 142 mg of azobisisobutyronitrile (AIBN), followed by stirring overnight at 80C. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3), thereby obtaining 4.44 g of benzyl 5-(bromomethyl)thiophene-2-carboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; ethanol; sodium methansulfinate; | Methyl 5-(methylsulfonylmethyl)thiophene-2-carboxylate may be prepared in the following manner: 6.94 g of sodium methanesulfinate are added, at room temperature, to a solution of 16 g of <strong>[108499-32-7]methyl 5-bromomethylthiophene-2-carboxylate</strong> in 150 cm3 of tetrahydrofuran. The suspension is stirred for 2 hours 30 min under reflux, and then after addition of 50 cm3 of ethanol is again stirred for 3 hours under reflux. The mixture is concentrated to dryness under reduced pressure (2.7 kPa) and the residue obtained is supplemented with 150 cm3 of distilled water and is then extracted with twice 300 cm3 of ethyl acetate. The organic phase is successively washed with 100 cm3 of distilled water and twice 50 cm3 of saturated aqueous sodium chloride solution and then dried over magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa). 14 g of methyl 5-(methylsulfonylmethyl)thiophene-2-carboxylate are thus obtained in the form of a yellow solid melting around 133 C. [1H NMR spectrum (400 MHz, (CD3)2SO-d6, at a temperature of 373 K, delta in ppm): 3.05 (s, 3H), 4.22 (mt, 2H), 4.40 (mt, 2H), 4.98 (broad s, 1H), 7.30 (d, J=3.5 Hz, 1H), 7.39 (d, J=8 Hz, 4H), 7.50 (d, J=8 Hz, 4H), 7.66 (d, J=3.5 Hz, 1H)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | In acetic acid; N,N-dimethyl-formamide; mineral oil; | EXAMPLE 4 A solution of 8-chloro-10,11-dihydrodibenzo[b,f][1,4]-thiazepine (Coll. Czech. Chem. Comm., 1959, 24, 207; 2 g) in DMF (20 ml) was added dropwise to a stirred suspension of sodium hydride (60% w/v dispersion in mineral oil, 0.38 g) in DMF (5 ml) which had been cooled to 0 C. The mixture was stirred at 0 C. for 30 minutes. A solution of <strong>[108499-32-7]methyl 5-bromomethylthiophene-2-carboxylate</strong> (1.89 g) in DMF (5 ml) was added dropwise. The mixture was allowed to warm to ambient temperature and was stirred for 18 hours. The mixture was poured onto ice and acidified by the addition of glacial acetic acid. The mixture was extracted with diethyl ether (3*50 ml). The combined extracts were washed with water and with brine, dried (MGSO4) and evaporated. The residue was purified by column chromatography using a 3:2 v/v mixture of hexane and methylene chloride as eluent. There was thus obtained methyl 5-(8-chloro-10,11 -dihydrodibenzo[b,f][1,4]thiazepin-10-ylmethyl)thiophene-2-carboxylate in 13% yield. The product so obtained was hydrolyzed using an analogous procedure to that described in the second paragraph of Example 1. There was thus obtained 5-(8-chloro-10,11-dihydrodibenzo[b,f][1,41-thiazepin-10-ylmethyl)thiophene-2-carboxylic acid in 61% yield, m.p. 216-217 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; dichloromethane; water; ethyl acetate; | 5-Cyanomethyl-2-carbomethoxythiophene (III-4) A mixture of III-3 (18.0 g, 76.6 mmol), sodium cyanide (15.0 g, 0.31 mmol), benzyltrimethylammonium chloride (1.75 g, 9.4 mmol), dichloromethane (75 mL), and water (75 mL) was stirred rapidly for 16 hours. The mixture was then separated. The organic layer was treated first with water (75 mL), then with sodium cyanide (15.0 g, 0.31 mmol), and last with benzyltrimethylamonium chloride (1.5 g, 8.0 mmol). This mixture was again rapidly stirred for 24 hours. The organic layer was removed, dried over magnesium sulfate, and concentrated. The residue was chromatographed on 250 g of flash silica gel using 20% ethyl acetate in hexane as an eluent, to give the product (III-4) as a yellow crystalline solid, 4.53 g (33%). Analysis gave the following results. NMR (CDCl3) d 7.66 (d, 1H, C3 -H); 7.03 (d, 1H, C4 -H); 3.83 (d, 5H, CH3 +CH2); mass spectrum m/e 196 (M +H); TLC (10% ethyl acetate in hexanes on silica gel plates); Rf -0.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | Preparation 20 Methyl 5-(bromomethyl)-2-thiophene carboxylate The title compound of Preparation 19 (1.9 g, 12.2 mmol), N-bromosuccinimide (NBS, 2.2 g, 12.4 mmol), and benzoyl peroxide (20 mg, 0.08 mmol) were combined with 125 ml CCl4 under an inert atmosphere at room temperature. The reaction mixture was heated to 87 for 4 hrs. An additional 540 mg of NBS (3.0 mmol) and 75 mg of benzoyl peroxide (0.3 mmol) were then added and the reaction mixture was stirred for another hour at 87. The reaction mixture was filtered while hot and the filtrate was stripped to provide the title compound of this Preparation (811 mg, 28% yield) as a brown oil. 1 H NMR (CDCl3): delta 7.63 (1H, d, J=4), 7.09 (1H, d, J=4), 4.68 (2H, s), 3.89 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; In tetrachloromethane; | Preparation of 5-Bromomethyl-thiophene-2-carboxylic acid methyl ester (T-1). 5-Methyl-thiophene-2-carboxylic acid methyl ester (20.0 g, 0.13 mol) was dissolved in a suspension of N-bromosuccinimide (45.4 g, 0.26 mol) and 2,2'-aza-bis-isobutyronitrile (0.1 g, 0.61 mmol) in 1 L of carbon tetrachloride. The suspension was refluxed for 48 hours then cooled and the precipitate was filtered off. The filtrate was concentrated and the residue was purified on silica gel (100% hexanes then 9:1 Hexanes-Ethyl acetate) to provide a 26 g fraction containing mainly the di-brominated compound 5-dibromomethyl-thiophene-2-carboxylic acid methyl ester as a yellow oil and a more polar fraction (7.5 g) containing mainly compound T-1 (25% yield) as a yellow oil (70% purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | [203] Step 3. Alkylation of 3 with B to give 4; [204] Sodium hydride (9 mg of a 60% dispersion in oil, 0.23 mmol) was added to a solution of 3 (40 mg,0.15 mmol) in DMF (0.36 mL) at 0 0C. The mixture was allowed to warm to room temperature. After 30 min <n="29"/>at room temperature, a solution of B (see US Provisional Patent Application No. 60/804,680, filed June 14, 2006, incorporated by reference herein, 29 mg, 0.12 mmol) in DMF (0.36 mL) was added. After 10 min the reaction was partitioned between water (10 mL) and CH2CI2 (20 mL). The phases were separated and the aqueous phase was extracted with CH2CI2 (2x10 mL). The combined organic phase was dried (MgSO-t), filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography on 4 g silica (hexane -> EtOAc, gradient) to afford 20 mg (38%) of 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Step 2. Alkylation of 56 to Give 57; Sodium hydride (60% dispersion in oil, 26 mg, 0.65 mmol) was added to a solution of alcohol 56 (120 mg, 0.44 mmol) at 0 C. and the mixture was allowed to warm to room temperature. After 20 minutes, the mixture was cooled to -40 C. and a solution of <strong>[108499-32-7]methyl 5-(bromomethyl)thiophene-2-carboxylate</strong> (125 mg, 0.53 mmol) in DMF (1.1 mL) was added via cannula. After 1 hours at -40 C. the reaction was quenched with 0.5 N HCl (15 mL) and extracted with EtOAc (3×30 mL). The combined extracts were washed with water (2×20 mL) and brine (20 mL) then dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified on 12 g silica (hexanes?EtOAc, gradient) to afford 84 mg (45%) of 57. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | Sodium hydride (60% oil dispersion, 40 mg, 1.0 mmol) was added to a solution of alcohol 10 (200 mg, 0.51 mmol) in DMSO (1.25 mL) at room temperature. After 30 <n="18"/>min at room temperature, a solution of bromide B (see Allergan docket No.17833, 130 mg, 0.55 mmol) in DMSO (1.25 mL) was added via cannula. After 15 min at room temperature, the mixture was heated at 40 0C. After 16 h at 40 0C, the mixture was allowed to cooled to room temperature, quenched with saturated aqueous NH4Cl (5 mL) and 0.5 N HCl (15 mL) and extracted with EtOAc (3x40 mL). The combined extracts were washed with H2O (2x20 mL) and brine (20 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 4 g of silica gel (hexane - > EtOAc, gradient) afforded 36 mg (13%) of desired product 11. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Sodium hydride (60% oil dispersion, 16 mg, 0.40 mmol) was added to a solution of alcohol 3 (99 mg, 0.28 mmol) DMF (0.7 mL) at 0 0C. After 5 min, the reaction was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to - 40 0C and a solution of bromide B (see United States Provisional Patent Application No. 60/804,680, filed on June 14, 2006, 54 mg, 0.23 mmol) in DMF (0.7 mL) was added via cannula. After 2 h at - 40 0C, the reaction was quenched with 1.0 N HCl (10 mL) and extracted with EtOAc (3x30 mL). The combined extracts were washed with H2O (2x20 mL) and brine (20 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 4 g of silica gel (hexane - > EtOAc, gradient) afforded 83 mg (59%) of desired product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis Example 14-2: Synthesis of 5-(N-Boc-N-2-picolylamino methyl) thiophene-2-carboxylic acid (Compound VII-7) 513 mg of the compound obtained in Synthesis Example 14-1 was dissolved in 10 ml of DMF, and then 603 mg of potassium carbonate and 0.45 ml of 2-picolylamine were added to the solution. After 17 hours, the reaction solution was concentrated and then water was added thereto, followed by extraction with chloroform. An organic layer was washed with a saturated salt solution and was then dried with anhydrous sodium sulfate. The residue obtained by concentrating the layer was dissolved in 6 ml of dioxane, and then 0.55 ml of di-t-butyldicarbonate and 6 ml of a 1 mol/l sodium hydroxide aqueous solution were added to the solution. After 6 hours, about 2 ml of a 1 mol/l sodium hydroxide aqueous solution was added to the reaction solution. Then, the solution was further stirred for 4 hours. The reaction solution was concentrated and water and 1 mol/l hydrochloric acid were added to the solution to be slightly acidic. Then, the solution was extracted with chloroform. An organic layer was dried with anhydrous sodium hydroxide and concentrated. The resulting residue was dissolved in 12 ml of methanol, to which 12 ml of a 1 mol/l sodium hydroxide aqueous solution was added. After 16 hours, the reaction solution was concentrated and dissolved in water, followed by gradually adding 1 mol/l hydrochloric acid to adjust to pH 4 to 5. After the solution was left to stand for overnight, a precipitated solid was filtrated and dried under reduced pressure. Consequently, 523.3 mg of the above-mentioned material was obtained as a white solid product. MS(FAB,Pos.):m/z=349[M+1]+ 1H-NMR(500MHz,CDCl3): delta=1.50 and 1.55 (9H,2s), 4.52, 4.60, 4.64 and 4.69 (4H,4s),6.93 and 6.97 (1H,2d,J=3.7Hz), 7.33 (1H,dd,J=5.6, 7.1Hz), 7.37 and 7.50 (1H,2d,J=7.6Hz), 7.67 (1H,d,J=3.7Hz), 7.80 (1H,t,J=7.3Hz), 8.69 (1H,brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis Example 15-1: Synthesis of 2-methoxycarbonyl-5-(N-(imidazol-2-ylmethyl) aminomethyl) thiophene (Compound V-5) 2.02 g of the compound obtained in Synthesis Example 14-1 was dissolved in 30 ml of DMF, and then 1.92 gof potassiumphthalimide was added to the solution. After 3.5 hours, the reaction solution was concentrated and then water was added thereto, followed by extraction with chloroform. An organic layer was dried with anhydrous sodium sulfate and concentrated. The resulting residue was re-crystallized frommethanol, and 1.52 gof the above-mentioned compound was obtained as a yellow solid product. 714 mg of the compound was dissolved in 3.6 ml of ethanol, and then 0.57 ml of hydrazine monohydrate was added to the solution. After the 20-hours reaction, the reaction solution was concentrated. The resulting solid product was washed with chloroform. Filtrate was concentrated and then the resulting residue was dissolved in 14 ml of methanol. Subsequently, 232 mg of 2-imidazole carboxyaldehyde and 0.34 ml of triethylamine were added to the solution and the resultant mixture was stirred for 20 hours. Then, 183 mg of sodium borohydride was added to the reaction mixture. After additional 2 hours, a small amount of silica gel was added to the reaction solution and the solution was concentrated. The resulting residue was purified by means of silica gel column chromatography (15 g, chloroform/methanol = 20/1). Consequently, 105 mg of the above-mentioned compound was obtained as yellow syrup. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Step 3. Alkylation of 4 with 5 to give 6 <n="20"/>[133] Sodium hydride (21 mg of a 60% dispersion in oil, 0.53 mmol) was added to a solution of 4 (100 mg, 0.35 mmol) in DMF (0.43 mL) at 00C and the mixture was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to -40 0C and a solution of bromide 5 (see US Provisional Patent Application 60/804,680, filed June 14, 2006, 70 mg, 0.30 mmol) in DMF (0.43 mL) was added via cannula. After 10 min at -40 0C, the reaction was partitioned between water (10 mL) and CH2CI2 (20 mL). The phases were separated and the aqueous phase was extracted with additional CH2CI2 (2x10 mL). The combined organic phase was dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by chromatography on silica gel (hexanes ? EtOAc, gradient) to afford 84 mg (64%) of 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Sodium hydride (60% oil dispersion, 7 mg, 0.18 mmol) was added to a solution of alcohol 3 (50 mg, 0.12 mmol) in THF (0.4 mL) and DMF (0.2 mL) at 0 C. After 5 min, the reaction was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to a -40 C. and a solution of bromide B (see U.S. Provisional Patent Application No. 60/804,680, filed on Jun. 14, 2006, incorporated by reference herein, 33 mg, 0.14 mmol) in THF (0.1 mL) and DMF (0.05 mL) was added via cannula. After 2.5 h at -40 C., the reaction was quenched with 0.5 N HCl (5 mL) and extracted with EtOAc (3×15 mL). The combined extracts were washed with H2O (2×5 mL) and brine (10 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 4 g of silica gel (hexane?EtOAc, gradient) afforded 44 mg (65%) of desired product 4. | |
65% | Sodium hydride (60% oil dispersion, 7 mg, 0.18 mmol) was added to a solution of alcohol 3 (50 mg, 0.12 mmol) in THF (0.4 mL) and DMF (0.2 mL) at 0 C. After 5 min, the reaction was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to a -40 C. and a solution of bromide B (see U.S. patent application Ser. No. 11/758,792, filed on Jun. 6, 2007, incorporated by reference herein, 33 mg, 0.14 mmol) in THF (0.1 mL) and DMF (0.05 mL) was added via cannula. After 2.5 h at -40 C., the reaction was quenched with 0.5 N HCl (5 mL) and extracted with EtOAc (3×5 mL). The combined extracts were washed with H2O (2×5 mL) and brine (10 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 4 g of silica gel (hexane?EtOAc, gradient) afforded 44 mg (65%) of desired product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; at -40 - -20℃; for 1.16667h; | Examples 6 and 7; 5-((((2S,3R)-3-chloro-1-(4-(1-hydroxyhexyl)phenyl)pyrrolidin-2-yl)methoxy)methyl)thiophene-2-carboxylic acid (26) and 5-((((2S,3R)-3-chloro-1-(4-((E)-hex-1-enyl)phenyl)pyrrolidin-2-yl)methoxy)methyl)thiophene-2-carboxylic acid (27)Step 1. Alkylation of 21 to give 22A solution of 21 (150 mg, 0.64 mmol) and bromide C (179 mg, 0.76 mmol) in DMF (0.45 mL) and THF (1.8 mL) was cooled to between -40 C. and -20 C. Sodium hydride (51 mg, 1.27 mmol) was added portionwise over 10 min. After 1 h stirring between -40 C. and -20 C., the reaction was quenched with water (3 mL) and extracted with CH2Cl2 (4×5 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue on silica (hexanes:CH2Cl2) afforded 169 mg (68%) 22 as a pale yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Step 2. Alkylation of 2 to Give 3; Sodium hydride (60% oil dispersion, 26 mg, 0.65 mmol) was added to a solution of alcohol 2 (180 mg, 0.44 mmol) in DMF (1.1 mL) at 0 C. After 5 min, the reaction was allowed to warm to room temperature. After 30 min at room temperature, the mixture was cooled to a -40 C. and a solution of bromide B (Preparation 1, 125 mg, 0.53 mmol) in DMF (1.1 mL) was added via cannula. After 3 h at -40 C., the reaction was quenched with 1 N HCl (10 mL) and extracted with EtOAc (3×30 mL). The combined extracts were washed with H2O (2×15 mL) and brine (20 mL), then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude residue by flash column chromatography on 12 g of silica gel (hexane?EtOAc, gradient) afforded 97 mg (39%) of desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In N,N-dimethyl-formamide; | Synthetic Methods While there are many ways to prepare the compounds disclosed herein, one exemplary synthesis may begin with L-serine methyl ester hydrochloride (1, see Scheme 1). Sequential silylation, amide formation and cyclization with triphosgene provides hydantoin 2 according to the procedures of Zhang, et al., J. Org. Chem. 2006, 71, 1750-1753. The dimethoxybenzylamide is chosen for its ease of deprotection under mild oxidative conditions, but many other protecting groups may be useful in this regard. Palladium- or copper-catalyzed reaction of 2 with bromide A gives arylated product 3 according to the procedures of Buchwald (for Cu, see J. Am. Chem. Soc. 2002, 124, 7421-7428; for Pd, see Org. Lett. 2000, 2, 1101-1104). A wide variety of substituted bromophenyl and other bromoaryl analogs of A may be employed. The haloarenes A are either available commercially or may be made according to published literature procedures. For example, U.S. patent application Ser. No. 11/009,298, filed on Dec. 10, 2004 and U.S. Provisional Patent Application 60/742,779 filed on Dec. 6, 2005, both of which are expressly incorporated by reference herein, disclose methods of making a number of useful substituted bromophenyl compounds. These procedures may also be readily adapted to other bromoaryl compounds such as substituted bromothienyl, substituted bromofuryl, substituted bromopyridinyl, substituted bromonaphthyl, substituted bromobenzothienyl, and the like. Deprotection of 3 gives alcohol 4. Alkylation of 4 with bromide B (prepared according to the procedure of U.S. Provisional Patent Application No. 60/804,680, filed on Jun. 14, 2006, expressly incorporated by reference herein) gives ester 5. Similar procedures may be carried out by substituting the thienyl of B with phenyl (i.e. X-CH2-phenyl-CO2H) or another heteroaromatic ring such as furyl, pyridinyl, etc. These compounds are commercially available, or may be readily prepared by art recognized methods. Deprotection of 5, followed by saponification affords the target compound 6. Conversion of compound 6 to compounds 23L and 23M is accomplished by a reaction path known in the art.Methods of forming compounds as in scheme 1 can be accomplished by methods taught in U.S. patent application Ser. No. 11/938,902, filed on Nov. 13, 2007 which is expressly incorporated by reference herein. In the event that the acidic NH bond in the compounds is not compatible with the ester formation step taught in Ser. No. 11/938,902, the deprotection of the N-P moiety is delayed until the last step. Foe example, steps g, h, and l in scheme 1, could be conducted in the order h, l, then g if the ester formation step is not possible. This can also hold true for schemes 2 and 3 below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 20℃; for 18h; | 1-(Cyclopropylmethyl)-3-(4-(piperazine-1~carbonyl)phenyl)urea (4.25mmol,1.286g), methyl 5-(bromomethy.)thiophene-2-carboxylate (4.25mmol, 1g) and potassium carbonate (12.76mmol, 1.764g) were stirred at room temperature in acetonitrile (2OmL) for 18 hours. The reaction mixture was concentrated at reduced pressure and the resulting residue taken up in dichloromethane, washed with water, dried over sodium sulfate and concentrated under vacuum to afford the title compound (1.764g). MS (ESI) m/z 457.5 [M+Hj+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With diisopropylamine; In ethanol; at 20 - 90℃; for 16h; | Preparation 17; Ethyl 5-(spiro[indene- 1 ,4'-piperidine]- 1 '-ylmethyl)thiophene-2-carboxylateMethod A To a solution of spiro[indene-l,4'-piperidine] (1.4 g, 6.3 mmol) in ethanol (28 mL) is added <strong>[108499-32-7]methyl 5-(bromomethyl)thiophene-2-carboxylate</strong> (1.78 g, 7.6 mmol) and diisopropylamine (3.31 mL, 19 mmol) at room temperature and the reaction mixture is stirred for 16 hours at 90 C. The mixture is concentrated, diluted with water, and extracted with ethyl acetate (2 x 200 mL). The combined extracts are washed with water (50 mL) and saturated brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the title compound (1.5 g, 58%). ESI/MS m/z 340.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Method B; Spiro [indene-1, 4'-piperidine] hydrochloride (128.0 g, 560 mmol) is dissolved in ethanol (1.5 L) under a nitrogen atmosphere at 30 C. Diisopropylethylamine (407.4 mL, 1.68 mol) is added dropwise at 30 C over a period of 10 minutes, and is stirred for 20 minutes. Methyl 5-(bromomethyl) thiophene-2-carboxylate (~50 % pure by LCMS) (300 g, 1.27 mol) is added at 30 C and stirred at 30 C for 10 minutes and the mixture is heated to 60 C for 1 h 45 min. The reaction is monitored by TLC showed the presence of starting material. The reaction is stirred for 13 hours at 30 C. The reaction mixture is concentrated and dissolved in DCM (10 L). HQ (1 N, 1.5 L) is added dropwise with constant stirring and a white solid precipitates and is collected. The material is dissolved in DCM (1 L), stirred for 10 minutes, filtered, and dried under vacuum (44 C) to give the title compound (150.0 g, 76%). ESI/MS m/z 340.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5-Bromomethyl-2-thiophenecarboxylic acid methyl ester (2.6 g, 10.4 mmol) and chloro(1,5-cyclooctadiene)rhodium(I) dimer (0.5 g, 1.02 mmol) were dissolved in formic acid (30 mL), and the mixture was stirred at 75C overnight under a carbon monoxide atmosphere. After evaporation of the solvent, thionyl chloride (10 mL) was added, and the mixture was stirred at 70C for 1 hr. The solvent was evaporated under reduced pressure, tert-butanol (10 mL) and triethylamine (2 mL) were added, and the mixture was stirred for 30 min. After evaporation of the solvent, water was added, and the mixture was extracted with ethyl acetate. The extract was concentrated and purified by silica gel column chromatography to give an oil (0.62 g). The oil (0.42 g) was dissolved in methanol (4.1 mL), 1N aqueous lithium hydroxide solution (4.1 mL) was added, and the mixture was stirred for 2 hr. The reaction mixture was neutralized with 1N hydrochloric acid (5 mL), purified by high performance liquid chromatography and freeze-dried to give the title compound (29 mg). 1H-NMR(400MHz, CDCl3) delta 7.74(1H, d, J=4.0Hz), 6.96(1H, d, J=4.0Hz), 3.78(2H, s), 1.48(9H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 5-chloropyridin-3-ol (3.64g, 28.1 mmol) in ACN (77mL) and DMF (7.73mL)vas added Cs2C03 ( 12.47g, 38.3mmol). The reaction mixture was stirred for l Omin and cooled down in an ice bath. A solution of methyl 5-(bromomethyl)thiophene- 2-carboxylate (6.0g, 25.5mmol) in ACN (20mL) was then added dropwise using an addition funnel. The reaction mixture was stirred for 2h and was then concentrated down, before being taken back in water and EtOAc. The organic phase was washed by water and brine, then dried over Na2S04 and filtered. Crude product was filtrated through a silica gel column with 30% EtOAc in hexanes, to afford the desired product (5.3g) as a light brown solid, LC-MS (ES) m/z = 284.0, 286.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 5h;Inert atmosphere; | To a solution of methyl-5-(bromomethyl)thiophene-2-carboxylate (27.8g, 1 1 8mmol) in DMF ( 1 70mL) under nitrogen atmosphere was added at room temperature 5-chloro-2- methylpyridin-3-ol (17g, 1 1 8mmol) followed by K2C03 ( 16.36g, 1 I Smmol). The reaction mixture was stirred for 5 h, before being diluted with water (340mL) and extracted with EtOAc (600mL). The separated organic phase was dried over Na2S04, filtered and concentrated under reduced pressure to afford the desired product (27g) as an off white solid, LC-MS (ES) m/z = 297.0, 299.0 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 20℃; | Add methyl-5-(bromoethyl)thiophene-2-carboxylate (432.5 g, 1.84 mol) in EtOH (500 ml) to a solution of 8-methoxy-l,2,3,4-tetrahydroquinoline (300 g 1.84 mol) in EtOH (1 L) and stir. Add DIPEA (641 ml, 3.67 mol) dropwise and stir at room temperature overnight. After completion of the reaction, remove the EtOH in vacuo, and add water (5 L). Extract the aqueous with EtOAc (3 x 3 L); combine the organic layers; and dry over sodium sulfate. Filter the solution and concentrate under reduced pressure to give a residue. Purify the residue by silica gel flash chromatography eluting with ethyl acetate: hexane (6:94) to give the title compound (325 g, 56%). ESI (m/z) 318(M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | General procedure: A mixture of 4H-furo[3,2-b]indole-2-carboxylate (1 equiv) and NaH (3 equiv, 60%) in anhydrous DMF (5 mL) was stirred for 5 minat room temperature. A substituted-benzyl halide or heteroarylmethyl halide (4 equiv) was then added dropwise. The mixture was stirred at room temperature for 20 min. To this mixture was added 50 mL of ice cold water, and the solution was extracted with EtOAc. The organic phase was separately dried over anhydrous MgSO4, filtered, and evaporated under vacuum. The residue was purified by column chromatography on silica gel eluted with EtOAc:n-hexane (1:3, v/v) and then recrystallized from n-hexane/ EtOAc to obtain the pure compound (5a-o, 9a-c). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In water; N,N-dimethyl-formamide; at 0℃; for 4h;Inert atmosphere; | A solution of NaCN (787 mg, 16.0 mmol) in water (2 ml) was added drop wise to a solution of Methyl 5- (bromomethyl) thiophene-2-carboxylate 14, (2,6 g, 11.06 mmol) in DMF (18 ml.) at 0 C in argon atmosphere. The reaction mixture was stirred for 4 hrs. After completion of reaction (TLC) added saturated ammonium chloride solution (50 mL) and extracted with dichloromethane (30 mL x 3) . Organics was combined, dried over Na2SO< and evaporated in vacuo. Crude material was purified on silica gel column (StOAc : Hexanes 1:4) to give the titled compound 15. (1.1 g, 55%). *H NMR (CHC13, 400 MHz): delta 7.62 (d, J=-3.6, 1H) , 7.10 (m, 1H) , 4.31 (s, 2H) , 3.89 (s, 3H) ; "C NMR (CHCI3, 100 MHz): delta 164.4, 138.6, 136.2, 133.2, 127.1, 62.4, 20.4, 17.0; [M+H] * = 182.3 (APCI+) |
Tags: 108499-32-7 synthesis path| 108499-32-7 SDS| 108499-32-7 COA| 108499-32-7 purity| 108499-32-7 application| 108499-32-7 NMR| 108499-32-7 COA| 108499-32-7 structure
[ 14282-72-5 ]
Ethyl 5-(bromomethyl)thiophene-2-carboxylate
Similarity: 0.96
[ 54796-51-9 ]
Methyl 4-(bromomethyl)thiophene-2-carboxylate
Similarity: 0.82
[ 62224-16-2 ]
Methyl 4-bromothiophene-2-carboxylate
Similarity: 0.79
[ 62224-19-5 ]
Methyl 5-bromothiophene-2-carboxylate
Similarity: 0.77
[ 7312-11-0 ]
Methyl 5-bromobenzo[b]thiophene-2-carboxylate
Similarity: 0.75
[ 14282-72-5 ]
Ethyl 5-(bromomethyl)thiophene-2-carboxylate
Similarity: 0.96
[ 50340-79-9 ]
5-(Methoxycarbonyl)thiophene-2-carboxylic acid
Similarity: 0.87
[ 67808-64-4 ]
Methyl 5-formylthiophene-2-carboxylate
Similarity: 0.87
[ 19432-69-0 ]
Methyl 5-methylthiophene-2-carboxylate
Similarity: 0.87
[ 156910-49-5 ]
5-(Ethoxycarbonyl)thiophene-2-carboxylic acid
Similarity: 0.84
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 :