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. : | 135544-68-2 | MDL No. : | MFCD02684388 |
Formula : | C8H9NO5 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OIXALTPBNZNFLJ-UHFFFAOYSA-N |
M.W : | 199.16 | Pubchem ID : | 11788855 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.38 |
Num. rotatable bonds : | 5 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 47.95 |
TPSA : | 72.91 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.32 cm/s |
Log Po/w (iLOGP) : | 1.8 |
Log Po/w (XLOGP3) : | 0.28 |
Log Po/w (WLOGP) : | 0.01 |
Log Po/w (MLOGP) : | -0.07 |
Log Po/w (SILICOS-IT) : | 0.12 |
Consensus Log Po/w : | 0.43 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.92 |
Solubility : | 23.9 mg/ml ; 0.12 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.37 |
Solubility : | 8.44 mg/ml ; 0.0424 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.39 |
Solubility : | 81.3 mg/ml ; 0.408 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.32 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P280-P302+P352-P337+P313-P362+P364-P332+P313 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
With triethylamine; In tetrahydrofuran; water; at 20℃; | 8-B: trans-4-Hydroxyproline (Hyp-OH) (7.90 g, 60.1 mmol) and <strong>[135544-68-2]N-(allyloxycarbonyloxy)succinimide</strong> (12.0 g, 60.1 mmol) are added to a round bottomed flask containing THF (220 mL), triethylamine (21 mL, 150.3 mmol) and water (55 mL). The mixture is stirred at room temperature overnight. The clear solution is acidified with 1N HCl (100 mL) and extracted with EtOAc (4×150 mL). The combined organic layer is washed with brine (100 mL) and dried with MgSO4. Solvent is evaporated in vacuo to afford the desired product as a white solid, which is used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In water; acetonitrile; for 3h; | Commercially available Kynurenine (3 g) was suspended in acetonitrile (100 mL) and water (30 mL). Diisopropylethylamine (DIPEA, 5.0mL) was added dropwise to the solution and stirring was continued until the solution was homogeneous. The solution was then cooled to 0 C. in an ice/sodium chloride bath and a solution of allyloxycarbonyl oxysuccinimide (AllocOSu, 4.3 g) in acetonitrile (30 mL) was added. The reaction mixture was stirred for 3 hours then concentrated to remove acetonitrile, basified with 5% K2CO3 solution (220 mL) and washed with ethyl acetate (5×90 mL) and dichloromethane (1×90 mL). The aqueous portion was then acidified to pH 1 and extracted with ethyl acetate (4×90 mL). Combined acidic organic washes were dried with anhydrous MgSO4 and evaporated to give crude product (4.85 g). Purification by column chromatography on silica gel, eluting with dichloromethane methanol 19:1, gave the desired intermediate, L-2-N-(allyloxycarbonyl)-4-(2-aminophenyl)-4-oxobutanoic acid, after evaporation of the solvent as a yellow solid 2.92 g. This solid (2.9 g) was dissolved in 4N HCl (100 mL) and cooled to 0 C. in an ice/sodium chloride bath. A solution of NaNO2 (0.76 g) in water (10 mL) was added dropwise such that the temperature remained below 3 C., and the resultant solution was stirred for 2.5 hours at 0 C. A solution of NaN3 (1.95 g) in water (10 mL) was added dropwise such that the temperature remained below 3 C. and the resultant solution was warmed to ambient temperature and stirred over 19 hours. The reaction mixture was poured into water (250 mL) and extracted with dichloromethane (4×100 ml). The combined organic washes were dried with anhydrous MgSO4 and evaporated to the desired product compound 25 (2.86 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; for 17h; | Commercially available Isoleucine (22 g) was added to a solution of allyloxycarbonyl oxysuccinimide (AllocOSu, 51 g) in tetrahydrofuran (150 mL). Ten percent K2CO3 aqueous solution (100 mL) was added to this suspension and the mixture was stirred for 17 hours before concentrating to approximately 120 ml under reduced pressure. The solution was added to 10% K2CO3 aqueous solution (100 mL) and water (200 ml) and washed with diethyl ether (4×150 mL). The aqueous portion was then acidified to pH 1 and extracted with dichloromethane (4×200 mL). Combined acidic dichloromethane washes were dried with anhydrous MgSO4 and evaporated to crude product (38.1 g). Purification by column chromatography on silica gel, (eluting with dichloromethane/methanol gradient of 100% dichloromethane to dichloromethane: methanol 9:1) followed by evaporation of the solvent, gave the compound 124 as a yellow oil (36 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; water; at 20℃; for 1.58333h; | Example 41 Synthesis of Compound (41} <n="83"/>[00194] To a solution of Compound JlJ (730 g, 5 59 mmol) dissolved into H2O (28 mL) and THF (28 mL) was added Alloc-OSu (2.07 g, 1 1.18 mmol, 2 eq.) at room temperature. To the above mixture, DIPEA (1.4 mL) was added dropwise at room temperature (approx. 5 nun) After stirring at room temperature for 1.5 hour, the reaction mixture was then monitored by analytical HPLC until the reaction was complete. The volatile solvents were removed under reduced pressure, and the residual material was re-dissolved into MeOH (10 mL). This clear solution was poured slowly into ethyl ether (200 mL) with stirring. A mass of white precipitate formed rapidly 7.18 g of white solid Compound (41) was collected by filtration under vacuum |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; | (1. Alloc protection of the secondary amino group with allyloxycarbonyl-N- hydroxysuccinimide (AllocOSu) in CH2Cl2, 2. cleavage of the Boc group with dioxane-HCl;3. Teoc protection of the primary amino group with 2-(trimethylsilyl) ethyl 4-nitrophenyl carbonate (Teoc-ONp) in CH2Cl2 in the presence of Et3N) from amino alcohol 13, applying standard conditions; as leading references cf.T. W. Greene, P. G. M. Wuts, Protective Groups in OrganicSynthesis, 3rd edition, John Wiley & Sons, 1999;P.J. Kocienski, Protecting Groups, 3rd edition, Georg Thieme Verlag, 2005.Data of 16: Ci5H28N2O5Si (344.5): Flow injection MS (APCI): 689 ([2M+H]+), 345 ([M+H]+). 1H-NMR (DMSO-d6): 7.28 (d, J = 6.1, 1 H), 5.90 (m, 1 H), 5.25 (qd, J = 1.7, 17.2, 1 H), 5.16 (qd, J = 1.5, 10.5, 1 H), 4.90 (br. t, 1 H), 4.54-4.42 (m, 2 H), 4.04- 3.97 (m, 2 H), 3.90 (q, J = 6.8, 1 H), 3.80-3.66 (br. m and dd, 2 H), 3.57-3.43 (br. m, 2 H), 2.96 (br. m, 1 H), 2.19 (br. m, 1 H), 1.78 (br. m, 1 H), 0.89 (t, J ca 8.3, 2 H), 0.00 (s, 9 H) | |
In dichloromethane; | (2S,4S)-Allyl 2-(hydroxymethyl)-4-((2-(trimethylsilyflethoxy)-carbonylamino)pyrrolidine-1-carboxylate (16) was prepared from amino alcohol 13 in three steps by 1) alloc protection of the secondary amino group with <strong>[135544-68-2]allyloxycarbonyl-N-hydroxysuccinimide</strong> (AllocOSu) in CH2Cl2, 2) cleavage of the Boc group with dioxane-HCl, and 3) Teoc protection of the primary amino group with 2-(trimethylsilyl)ethyl 4-nitrophenyl carbonate (Teoc-ONp) in CH2Cl2 in the presence of Et3N) applying standard conditions.Data of 16: C15H28N2O5Si (344.5): Flow injection MS (APCI): 689 ([2M+H]+), 345 ([M+H]+). 1H-NMR (DMSO-d6): 7.28 (d, J=6.1, 1H), 5.90 (m, 1H), 5.25 (qd, J=1.7, 17.2, 1H), 5.16 (qd, J=1.5, 10.5, 1H), 4.90 (br. t, 1H), 4.54-4.42 (m, 2H), 4.04-3.97 (m, 2H), 3.90 (q, J=6.8, 1H), 3.80-3.66 (br. m and dd, 2H), 3.57-3.43 (br. m, 2H), 2.96 (br. m, 1H), 2.19 (br. m, 1H), 1.78 (br. m, 1H), 0.89 (t, J ca. 8.3, 2H), 0.00 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium hydrogencarbonate; In 1,4-dioxane; dichloromethane; water; ethyl acetate; | O-Allyl-O-(tert-butyl) N,N-ethane-1,2-diylbiscarbamate (86a). To a solution of tert-butyl (2-aminoethyl)carbamate (85a, 473 mg, 2.95 mmoles) in 15 mL of a mixture of dioxane and water (1:1) was added sodium bicarbonate (496 mg, 5.90 mmoles) and a solution of <strong>[135544-68-2]allyl N-succinimidyl carbonate</strong> (706 mg, 3.54 mmoles) in 1.5 mL of dioxane. The mixture was stirred for 2.5 h at room temperature. Ethyl acetate was added and the separated organic layer was collected. The aqueous layer was extracted twice more with ethyl acetate and the combined organic phases were washed with saturated brine, dried over MgSO4 and concentrated to dryness in vacuo. The residue was purified by two consecutive SiO2 chromatographies on a Biotage flash chromatography system using 0-50% ethyl acetate in hexanes and 0-30% ethyl acetate in CH2Cl2 as the respective eluents to furnish 86a (578 mg, 2.37 mmoles, 80% yield) as a solid. 1H NMR (400 MHz, CDCl3) delta 1.44 (s, 9H), 3.28 (m, 4H), 4.56 (d, J=5.5 Hz, 2H), 4.82 (broad s, 1H), 5.11 (broad s, 1H), 5.21 (broad dq, J=1.3, 10.4 Hz, 1H), 5.30 (dq, J=1.5, 17.2 Hz, 1H), 5.92 (octet, J=5.5 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.14 g | With triethylamine; In tetrahydrofuran; water; at 20℃; for 2h; | A solution of azide 4 (3.14 g, 8.77 mmol) in THF (70 mL) was treated with Ph3P (2.95 g, 11.4 mmol) and H2O (14 mL). After stirring at 70 C for 3 h, the reaction mixture was cooled to r.t. and AllocOSu (2.27 g, 11.1 mmol) and Et3N (1.84 mL, 13.2 mmol) were added.The solution was stirred at r.t. for 2 h, quenched with Et2NH(0.60 mL) and stirred for 15 min. After dilution with EtOAc (400mL), the mixture was washed with sat. aq NaHCO3 (150 mL). The aqueous phase was extracted with EtOAc (2 × 30 mL), and the combined organic phases were dried (MgSO4) and evaporated. Purificationof the residue by flash chromatography yielded carbamate 6 as a colorless oil; yield: 3.14 g (86%); Rf = 0.35 (PE-EtOAc, 2:1); [alpha]D21 -13.8 (c 1.03, MeOH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
310 mg | In dichloromethane; at 0℃; for 2h; | At 0 C., a soln of 73 (500 mg, 1.12 mmol) in CH2C12 (4.0 mE) was treated with TFA (3.0 mE) for 2 h and concentrated. Aq. workup (EtOAc, sat. aq. NaHCO3 soln; Na2504) afforded crude 74 which was dissolved in CH2C12 (4.0 mE). The soln was cooled to 0 C. A soln of AllocOSu (245 mg, 1.23 mmol) in CH2C12 (1.0 mE) was added drop- wise. Stirring was continued for 2 h followed by an aq. workup (CH2C12, sat. aq. NaHCO3 soln; Na2504) and FC (hexane/EtOAc 1:1) to yield 75 (310 mg, 64%). Data of 75: C22H26N2055 (430.5). EC-MS (method la): R1.68 (94), 431.1 ([M+H]). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine; In methanol; N,N-dimethyl-formamide; at 23℃; for 16h;Inert atmosphere; | To a stirred suspension of AmB (4.0 g, 4.3 mmol, 1.0 equiv.) in DMF:MeOH (75 mL: 75 mL) in a 300 mL round bottom at 23 C, was added sequentially, pyridine (5.0 mL, 50.0 mmol, 11.5 equiv.), and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for 16 h at 23 C, the dark orange, homogeneous solution was slowly poured into rapidly stirring Et20 (3.5 L). The yellow suspension was filtered through Whatman 42 filter paper and washed with Et20 (3 x 100 mL) before the cake was allowed to fully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken on to the subsequent reaction without further purification. |
100% | In methanol; N,N-dimethyl-formamide; at 23℃; for 16h; | To a stirred suspension of AmB (4.0 g, 4.3 mmol,1.0 equiv.) in DMF:MeOH (75 mE: 75 mE) in a 300 mE round bottom flask at 23 C. was added pyridine (5.0 mE, 50.0 mmol, 11.5 equiv.) and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for 16 hat 23 C., the dark orange, homogeneous solution was slowly poured into rapidly stirring Et20 (3.5 E). The yellow suspension was filtered through Whatman 42 filter paper (110 mm diameter) and washed with Et20 (3x100 mE) before the cake was allowed to fully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken on to the subsequent reaction without thrther purification. |
With pyridine; In methanol; N,N-dimethyl-formamide; at 23℃; for 16h; | To a stirred suspension of AmB (4.0 g, 4.3 mmol, 1.0 equiv.) in DMF:MeOH (75 mL: 75 mL) in a 300 mL round bottom flask at 23 C was added pyridine (5.0 mL, 50.0mmol, 11.5 equiv.) and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for16 h at 23 C, the dark orange, homogeneous solution was slowly poured into rapidlystirring Et20 (3.5 L). The yellow suspension was filtered through Whatman 42 filter paper(110 mm diameter) and washed with Et20 (3 x 100 mL) before the cake was allowed tofully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken onto the subsequent reaction without further purification. |
With pyridine; In methanol; N,N-dimethyl-formamide; at 20℃; for 16h; | To a stirred solution of Amphotericin B (25.0 g, 27.05 mmol) in DMF:MeOH (2:1, 750 ml) and pyridine (25 ml. 308.4 mmoi) was added allocsuccinimide (15.08 g, 75.75 mmoi) at room temperature. After 1 6h, the reaction mixture was poured into cold Et20. The resulting solid was filtered and dried under reduced pressure to provide a yellow solid. The solid compound was washed with diethyl ether (5 x 100 mL) to afford compound 2 I as a yellow solid. Compound 24 analysis: LC/MS (ESI) m/z 1006.4 [MH]. | |
15.08 g | With pyridine; In methanol; N,N-dimethyl-formamide; at 20℃; for 16h; | EXAMPLE 1 [0094] Compound 1 (FIGURE 1 A) was prepared as follows (Figure IB): Step 1 : To a stirred solution of Amphotericin B (25.0 g, 27.05 mmol) in DMF: MeOH (2:1, 750 ml) and pyridine (25 ml, 308.4 mmol) was added alloc-succinimide (15.08 g, 75.75 mmol) at room temperature. After 16 h, the reaction mixture was poured into cold Et20. The resulting solid was filtered and dried under reduced pressure to provide a yellow solid. The solid compound was washed with diethyl ether (5 x 100 mL) to afford Compound 1-1 as a yellow solid. Compound 1-1 analysis: LC/MS (ESI) m/z 1006.4 [M-H]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium hydrogencarbonate; In tetrahydrofuran; water; at 20℃; for 17h; | Water (200 mL) was added to mixture of L-homoserine 7 (9.00 g, 75.63 mmol) and NaHCO3 (9.58 g, 114 mmol). The reaction mixture was stirred for 10 min until the initial gas evolution subsided. A solution of AllocOSu (15.05 g, 75.6 mmol) in THF (150 mL) was added dropwise over a 1 h duration to the solution of L-homoserine, while being stirred. The reaction mixture was stirred at room temperature for 16 h, after which it was evaporated to almost complete dryness. A citric acid (150 mL of aq 10percent) solution was added to the residual mass and the acidic pH of the aq layer was verified. Sodium chloride was added in small portions, while the reaction mixture was stirred until no more sodium chloride appeared to dissolve in the solution. EtOAc (2*100 mL) was used for the extraction of the product. The organic layers were combined, dried over anhydrous MgSO4, and evaporated under reduced pressure to yield the crude product. Analytically pure 8 was separated from the crude product using column chromatography (50percent EtOAc in hexanes) as a white solid (10.07 g, 72percent). Rf (50percent EtOAc in hexanes) 0.41; mp 69-71 °C (crystallised from methanol); [alpha]D21 -26.14 (c=1, THF); IR (neat) 802, 922, 1003, 1161, 1258, 1285, 1362, 1385, 1420, 1451, 1535, 1651, 1694, 1694, 1775, 2338, 2361, 2882, 2943, 3329 cm-1; 1H NMR (400 MHz, DMSO-d6): delta=7.75 (d, J=8.4 Hz, 1H), 5.91 (ddd, J=17.2, 10.6, 5.4 Hz, 1H), 5.29 (ddd, J=17.2, 3.3, 1.6 Hz, 1H), 5.20 (dd, J=10.5, 1.4 Hz, 1H), 4.50 (d, J=5.4 Hz, 2H), 4.42 (dt, J=11.2, 8.8 Hz, 1H), 4.32 (td, J=8.7, 1.1 Hz, 1H), 4.19 (ddd, J=10.8, 8.7, 6.3 Hz, 1H), 2.40 (m, 1H), 2.17 (m, 1H); 13C NMR (101 MHz, DMSO-d6): delta=175.4, 155.6, 133.4, 117.3, 65.1, 64.7, 49.5, 28.1; HRMS (EI) calcd for C8H12NO4 [M+H]+: m/z 186.0761; found: m/z 186.0749. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | In tetrahydrofuran; at 20℃; | To a solution of compound A6 (1.42 g, 3.36 mmol, 1 eq) in THF (10 mL) was added Alloc-OSu (1.34 g, 6.72 mmol, 2 eq) and triethylamine (1.4 mL, 10.1 mmol, 3 eq). The mixture was stirred at rt overnight. The solvent was removed and the residue was purified by flash column chromatography (DCM: MeOH = 9:1) to give compound A7 (1.01 g, 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine; In tetrahydrofuran; at 20℃;Inert atmosphere; | To a solution of compound A6a (300 mg, 0.930 mmol, 1 eq) in THF (7 mL) was added Alloc-OSu (199.1 mg, 1.86 mmol, 2 eq) and triethylamine (0.51 mL, 3.72 mmol, 4 eq). The mixture was stirred overnight at room temperature under N2 atm. The solvent was removed and the residue was purified by flash column chromatography (DCM:MeOH = 9:1) to give compound A7A (284 mg, 0.70 mmol, 75%). LC-MS (ESI): 407.4 (M+1), 307.6 (M- Boc+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | A suitable fully protected intermediate was quickly generated from AmB (Scheme 3, FIG. 16). This sequence involved Alloc protection of the amine, C3/C5 and C9/C11 rho-methoxyphenyl acetal formation, TES silylation of the remaining alcohols, and lastly TMSE formation of the C16 carboxylate to form fully protected intermediate 5. Exposure of 5 to NaHMDS at low temperatures smoothly eliminated the C3 alcohol, generating an alpha-beta unsaturated lactone. Stryker reduction of this intermediate efficiently reduced the unsaturation yielding 6, leaving only a deprotection sequence to generate C3deOAmB. Exposure of 6 to HF cleanly removed the TES groups, followed by TBAF-promoted TMSE removal. Methyl ketal and PMP ketal hydrolysis was achieved concomitantly under acidic conditions with HCl. Efforts are currently underway to achieve the final Alloc deprotection of 7 and synthesize C3deOAmB. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium hydrogencarbonate; In water; acetonitrile; at 20℃;Cooling with ice; | To an ice-cold mixture of lH-indol-5-amine and NaHCC in a mixture of ACN (10 mL) and water (15 mL) was added a solution of allyl (2,5-dioxopyrrolidin-l -yl) carbonate in ACN (5 mL). The resulting mixture was stirred at room temp overnight, concentrated by rotary evaporation, and then EtOAc (60 mL) was added, the organic layer was washed with brine, dried over MgSC-4 and concentrated by rotary evaporation followed by purification on silica gel (0- 80% Hex:EtOAc) to afford allyl lH-indol-5-ylcarbamate (2). (1.54 g, 7.12 mmol, 94% yield).ESI MS: (M+H) 217.2; found 217.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium hydrogencarbonate; In water; acetone; at 20℃; for 16h; | <strong>[1115-74-8](S)-2-((S)-2-amino-3-methylbutanamido)propanoic acid</strong> (1.74 g, 9.24 mmol), allyl (2,5-dioxopyrrolidin-1-yl) carbonate (1.84 g, 1 eq), NaHCO3 (776 mg, 1 eq), water (37 mL) and acetone (37 mL) was stirred at room temperature for 16 h. The acetone was removed by rotary evaporation, the residue was diluted with water (250 mL) and the pH adjusted to 3 using concentrated HCl (17 mL), followed by extraction with EtOAc (3×400 mL). The organic layer was dried over Na2SO4, filtered and evaporated to give ((allyloxy)carbonyl)-<strong>[1115-74-8]L-valyl-L-alanine</strong> (89) as a white solid (2.28 g, 91% yield). 1H NMR (DMSO-d6) delta 12.49 (s, 1H), 8.12 (d, 1H), 7.14 (d, 1H), 5.97 (m, 1H), 5.14 (d, 1H), 5.09 (d, 1H), 4.23 (s, 2H), 1.98 (m, 1H), 1.13 (d, 3H), 0.80 (m, 6H) |
44% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 3h; | To a solution of NH2-<strong>[1115-74-8]Val-Ala</strong>-OH (941 mg, 5 mmol) in DMF ( 10 mL), added DIEA (1.73 mL, 10 mmol) and N-(Allyloxycarbonyloxy)succinimide (1.15 rnL, 7.5 mmol). Reaction mixture was stirred for 3 hr, quenched with water (3 mL) and stirred overnight. Solvent was removed in vacuo and the residue was diluted with HCl in water (40 mL, 0.25 M). After sonication, the precipitate was filtered off and dried thoroughly to afford 2 (600 mg, 44% yield). 1H NMR (500 MHz, DMSO-d6) delta: 12.48 (bs, 1H), 8.18 id. J= 7,0 Hz, 1H), 7, 16 id. ./ 9.4 Hz, 1H), 5.95-5.83 (m, IH), 5.28 (d, J= 15.8 Hz, 1H), 5.17 (d. J = 10.5 Hz, 1H), 4 ,47 (m, 2H), 4.18 (m, 1H). 3,87 (m, 1H). 1.94 (m, 1H), 1.26 (d, J= 7.6 Hz, 3H), 0.86 (dd, J = 14.6, 6.7 Hz, 6H). LC/MS: retention time 0.25 min. (ESI) C12H21N2O5: [M+H]+ 273; found 273. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.9% | With sodium hydrogencarbonate; In water; acetonitrile; at 20℃; for 16h;Cooling with ice; | Part B To an ice-cold mixture of compound 19 (710 mg, 2.189 mmol) and sodium bicarbonate (221 mg, 2.63 mmol) in ACN (3 mL) and water (5 mL) was added a solution of <strong>[135544-68-2]allyl (2,5-dioxopyrrolidin-1-yl) carbonate</strong> (480 mg, 2.408 mmol) in ACN (2 mL). The resulting mixture was stirred at room temp for 16 h. The reaction mixture was diluted with EtOAc (30 mL) and washed with brine. The organic phase was dried over MgSO4 and concentrated under vacuum. and then purified on silica gel (Hex:EtOAc, 0-80% B) to give tert-butyl (4-(5-(((allyloxy)carbonyl)amino)-1H-benzo[d]imidazol-2-yl)phenyl)carbamate (20) (625 mg, 69.9% yield). ESI MS: C22H24N4O4 (M+H) 409.2; found 408.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium hydrogencarbonate; In water; acetone; at 20℃; | To a solution of compound 14 (110 mg, 0.246 mmol) in acetone (1 mL) was added a solution of <strong>[135544-68-2]allyl (2,5-dioxopyrrolidin-1-yl) carbonate</strong> (54 mg, 0.271 mmol) in acetone (0.3 mL) followed by NaHCO3 (23 mg, 0.27 mmol) in water (0.3 mL). The mixture was stirred 3-4 h at room temperature at which point LCMS indicated the reaction was complete. The reaction mixture was diluted with EtOAc (45 mL) and subsequently washed with water (15 mL) and then brine (15 mL). The organic phase was dried over MgSO4 and concentrated under vacuum. The crude product was purified on silica gel (Hexane:EtOAc, 0-60% B) to give compound 15 as a yellow foam (59 mg, 45% yield). 1H NMR (CD3OD): delta 7.80-7.74 (4H, m), 7.60 (1H, brs), 7.30 (1H, d, J=8.8 Hz), 7.16-7.05 (2H, m), 6.73 (1H, s), 6.11-5.89 (1H, m), 5.50-5.32 (1H, m), 5.31-5.19 (1H, m), 4.66-4.62 (2H, m), 4.04 (3H, s), 1.53 (9H, s). ESI-MS: C28H31N6O5 (M+H) 531.2; found 530.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In acetonitrile; at 20℃; for 1h; | [98] Fmoc-Gln- H-0-CH2-C(Me)2COOH (335 mg, 0.66 mmol) was converted to its sodium salt as previously described, added to a 10-mL acetone solution of 14-daunorubicin HC1 (53 mg, 0.083 mmol) in the presence of 3 A molecular sieves, and the mixture stirred at room temperature for 48 h. After adding 10 mL of methanol, the mixture was centrifuged at 3000 rpm for 15 min. The supernatant was collected, dried in vaccuo and reconstituted in 4 mL of anhydrous ACN. Protection the aminoglycoside was carried out with the addition of Alloc-OSu (33 mg, 0.17 mmol) in the presence of 2 equivalents of NaHCCb (suspension) and stirring the mixture for 1 h at room temperature. Two-step FCC purification from (0281) DCM/ACN; DCM/(20%MeOH/DCM) afforded the title compound in 40% yield (40 mg, greater than 90% pure by LC-UV). Fmoc-deprotection of Fmoc-Gln-NH-0-CH2- C(Me)2C(0)-14-O-(Alloc-Dox) was performed with 1% DBU in 1 mL of anhydrous DMF at room temperature in 10 min. Trituration with 10 mL of ice-cold ether followed by (0282) centrifugation at 3000 rpm afforded a dark orange solid which was purified by HPLC (10 mM ammonium acetate/ACN) to afford 17 mg of crude H-Gln- H-0-CH2-C(Me)2C(0)-14- O-(Alloc-Dox) (compound 10b). (0283) [99] NMR (DMSO-d6, 400 MHz): delta 11.32 (s, 2H), 7.90 (m, 2H), 7.69 (m, 2H), 7.41 (m, 2H), 7.30 (m, 3H), 5.61 (s, 1H), 5.24 (m, 3H), 4.94 (s, 1H), 4.54 (d, 2H, J = 5.4 Hz), 4.46 (m, 1H), 3.99 (s, 3H), 3.87 (s, 2H), 3.81 (m, 1H), 3.64 (m, 1H), 2.96 (d, 1H, J = 18.5 Hz), 2.10 (m, 8H), 1.27 (s, 6H), 1.11 (d, 3H, J = 2.9 Hz); 13C NMR (DMSO-d6, 100 MHz): delta 210.0, 202.0, 174.5, 173.4, 172.7, 156.0, 154.5, 143.7, 140.6, 133.6, 127.6, 127.0, 125.3, 120.0, 116.8, 75.2, 66.7, 65.7, 64.1, 56.5, 46.6, 42.4, 40.1, 39.9, 39.7, 38.9, 31.2, 25.2, 22.1, 22.0, MS (ESI+): m/z (intensity), 1093.2 ([M+H]+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;Inert atmosphere; | Allyl(2,5-dioxopyrrolidin-1-yl)carbonate (3.5 mL, 22.4 mmol) was added slowly to a stirred solution of 2-((4-ethynylbenzyl)(piperidin-2-ylmethyl)amino)ethan-1-ol trifluoroacetic acid (8.6 g, 22.4 mmol) in DCM (100 mL). DIPEA (4 mL, 23 mmol) was added and the mixture stirred at room temperature under a nitrogen atmosphere overnight. Further DIPEA (4 mL, 23 mmol) was added to ensure the solution was basic. Water (100 mL) was added and the separated aqueous layer extracted with DCM (3 x 100 mL). The combined organic extracts were dried (Na2S04) and the solvent evaporated in vacuo to leave a yellow oil (11 g). This was purified by flash column chromatography using an increasing gradient from 10-70% EtOAc/hexane to give the product (7.13 g, 20.0 mmol, 89%) as a yellow oil. UPLC-MS (Basic 2 min): rt 1.15 min, m/z 357 [M+H]+ 1H NMR (400 MHz, CDCI3) delta ppm: H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.13 - 1.38 (m, 2 H) 1.41 - 1.59 (m, 4 H) 2.03 - 2.30 (m, 2 H) 2.59 - 2.68 (m, 2 H) 2.70 - 2.88 (m, 2 H) 3.06 (s, 1 H) 3.30 - 3.40 (m, 1 H) 3.55 - 3.85 (m, 4 H) 4.43 (br s, 1 H) 4.52 - 4.68 (m, 2 H) 5.16 - 5.39 (m, 2 H) 5.97 (br s, 1 H) 7.22 (d, J^7.66 Hz, 2 H) 7.41 (br d, J^7.91 Hz, 2 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate; In tetrahydrofuran; water; | L-Asp(OtBu)-OH (5.3 mmol) and Alloc-OSu(7.9 mmol) were dissolved in THF (20 mL). K2CO3 (2.7 mmol, 10% in water) was added and themixture was stirred overnight. After evaporation of THF, the mixture was diluted with 10% K2CO3(10 mL) and washed four times with diethyl ether (30 mL). The aqueous phase was acidied with 5%HCl to pH 3 and extracted four times with DCM (30 mL). The combined organic layers were driedover MgSO4 and concentrated under reduced pressure. The obtained crude material was purifiedwith column chromatography (DCM:methanol 200:1) to give the title compound (4.7 mmol, 89%).1H-NMR (500 MHz, Chloroform-d) delta 6.65 (s, 1H), 5.90 (m, 1H), 5.77 (d, J = 8.6 Hz, 1H), 5.23 (dq, J= 10.5, 1.3 Hz, 2H), 4.60 (m, 3H), 2.99 (dd, J = 17.2, 4.4 Hz, 1H), 2.77 (m, 1H), 1.44 (s, 9H). 13C-NMR(126 MHz, Chloroform-d) delta 175.5, 170.3, 156.0, 132.4, 118.0, 82.4, 66.1, 53.5, 37.6, 28.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.84 g | To the bis(phosphoric acid) salt of oritavancin 1 (20.0 g, 10.05 mmol) in DMF (800 mE) and H20 (200 mE) was added NaHCO3 (6.75 g, 80.44 mmol) and the mixture was stirred until all of 1 had dissolved. A solution of Allyl N-succinimidyl carbonate (7.0 g, 35.2 mmol) in DMF (10 mE) was added and the resulting solution was stirred at room temperature for 20 h. The solvents were removed in vacuo, water was added and the pH was adjusted to 4.5 by the addition of aqueous iN Rd. A mixture of acetone/Et20 (1:3, 250 mE) was added, the solid was filtered, washed with H20 and dried in vacuo to give 2(20.84 g). ESI-MS: (M+H) calculated forC94H,Q5C13N,QO3Q 1961; found 1961.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.498 g | With sodium hydrogencarbonate; In water; acetone; at 20℃; | To a solution of compound 9 (0.5 g, 2.64 mmol) and NaHCCh (0.222 g, 2.64 mmol) in water (10 mL) was added a solution of allyl (2,5-dioxopyrrolidin-l-yl) carbonate (0.526 g, 2.64 mmol) in acetone (10 mL). The mixture was then stirred overnight at room temperature. Acetone was removed under vacuum and the pH was adjusted to 1-2 with 1 N HC1 and then extracted with EtOAc (2 x 30 mL). The organic phase was concentrated under vacuum. The residue was suspended in acetonitrile and concentrated under vacuum to afford compound 10 as a colorless solid (0.498 g). ESI MS: calc for C10H16N3O& (M+H) 274.1; found 274.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium hydrogencarbonate; In water; acetonitrile; at 20℃;Cooling with ice; | To an ice-cold mixture of (S)-tert-butyl 2-amino-6-((tert- butoxycarbonyl)amino)hexanoate hydrochloride 15 (1.0 g, 2 95 mmol) and sodium bicarbonate (0.545 g, 6.49 mmol) in a solution of ACN (10 mL) and water (15 mL) was added a solution of ally (2,5-dioxopyrrolidin-l-yl) carbonate (0.646 g, 3 25 mmol) in ACN (5 mL). The ice bath was removed and the mixture was stirred overnight at room temperature. Acetonitrile was removed under vacuum and the reaction mixture was diluted with EtOAC (60 mL) and washed with brine. The organic phase s dried over MgSCri, filtered and concentrated under vacuum. The crude product was purified on silica gel (Hex:EtOAc, 0-80%B) to afford compound 16 (1.09 g, 2.82 mmol, 96% yield). ESI MS: calc for CiyEbi zNaOc, (M+Na) 409.2; found 409.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In water; acetone; at 20℃; for 12h; | Compound 23 (1 g, 8.54 mmol) and NaHCCb (0.717 g, 8.54 mmol) were dissolved in acetone (42.7 mL) and water (42.7 mL). Allyl (2,5-dioxopyrrolidin-l-yl) carbonate (1.700 g, 8.54 mmol) was dissolved in acetone (5 mL), and added to the reaction mixture, which was then stirred for 12 h at room temperature. The reaction mixture was then concentrated under reduced pressure, acidified by the dropwise addition of concentrated HC1 to pH 3, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2S04, and concentrated to provide crude Alloc- Val-OH (1.85 g, 9.19 mmol, 108% yield) ESI MS:C9H14NO4 (M-H) 200.1; found 200.0 (negative mode), which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium hydrogencarbonate; In water; acetone; at 20℃; for 12h; | To compound 95 (1.183 g, 4.19 mmol) was added acetone (6.98 niL), H2O (6.98 mL), NaHCCb (0.352 g, 4.19 mmol) and ailyl (2,5-dioxopyrrolidin-l-yl) carbonate (0.834 g, 4.19 mmol). The reaction mixture was stirred for 12 hours at room temperature, then diluted with H2O (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (3x20mL). The combined organic layers were dried over Na2S04, then concentrated. The crude product was purified on silica gel (0-10% MeOH in DCM) to provide compound 96 (1.37 g, 89 % yield) as a red-brown oil. ESI-MS calc for (A P -OO (M+H) 367 2; found 367.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In tetrahydrofuran; water; at 0 - 20℃; | To a solution of the L-alanine ( 1 g, 11.2 mmol) and K2.CG3 (3.1 g) in water ( 15 niL) at 0C was added a solution of Alloc-OSu (1.1 eqs, 2 21 g) in THF (15 mL). The resulting mixture was allowed to warm slowly to room temperature and stir overnight. The reaction mixture was concentrated, washed with ether (2x), the pH then adjusted from 11 to ~3, washed with EtOAc (3x) and the combined organic layers were dried over NaiSCE, evaporated to afford Alloc-alanine-OH as a clear oil (2.14g, 100 % yield). (2002) [01172] To a mixture of Alloc-alanine-OH (100 mg, 578 miho), Alanine Me ester.HCl (leq, 105 mg), HOAt (leq, 79 mg) in DMF (5 mL) was added TEA (4.5 eqs, 363 pL) and the resulting solution was stirred 5 minutes, followed by the addition of HATH (1 .3 eqs, 286 mg). After stirring overnight at room temperature, DMF was removed under vacuum. The residue in EtOAc was washed with water (3x), brine, dried over Na2S04 and concentrated to yield an off- white solid that was triturated in EtOAc to afford compound 22 as a brown oil, (138 mg, 80% yield) i l l NMR (CDCb): 6 6.45 (1 FI, d, ./ 6.7 Hz), 6 5.98-5.85 (1 H, m), d 5.36-5.26 (2 H, m), 5 5.26-5.18 (1 H, m), d 4.57 (2 H, d, J= 5.9 Hz), d 4.48-4.38 (1 H, m), d 4.28-4.16 (1 H, m), 6 1 47 (9 H, s), 1.43-1.35 (6 1 1, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydrogencarbonate; In water; acetone; at 20℃; for 12h; | Compound 42 (0.95 g, 3.13 mmol), K2CO3 (0.801 g, 5.79 mmol), ACN (25 mL) and 3-bromoprop-l-ene (0.501 mL, 5 79 mmol) were stirred for 12 hours at room temperature. The crude reaction mixture was filtered through a Celite plug, washed with DCM and the filtrate was concentrated and purified on silica gel (0-100 % EtOAc in Hexanes) to provide Boc-Glu(y- QAllyl)-0/-Bu (1.075 g, 94 % yield). ESI-MS: calc for CnH29N]SiaOy (M+Na) 366.2; found 366.2. (2037) [01193] To the intermediate Boc-Glu(y-OAllyl)-0/-Bu (1.075 g, 3.13 mmol) dissolved in DCM (15.65 mL), was added TEA (15.65 mL) and the reaction stirred for 12 hours at room temperature. The crude reaction mixture was concentrated to provide H-Glu(y-OAllyl)-OH (0.586 g, 3.13 mmol, 100 % yield). ESI-MS: calc for CSHMMV (M+H) 188.1; found 188.1. (2038) [01 194] The intermediate H-Glu(y-OAllyl)-OH (0 586 g, 3 13 mmol) was dissolved in water (15.65 mL) and acetone (15.65 mL), then NaHCCb (0.789 g, 9.39 mmol) and allyl (2,5- dioxopyrrolidin-l-yl) carbonate (0.623 g, 3.13 mmol) were added and the reaction mixture was stirred for 12 hours at room temperature. The crude reaction mixture was concentrated, then acidified to pH 3 using IN HC1, extracted with EtOAc, (3x) and the combined organic layers were washed with brine, dried over Na^SCfi and concentration to provided Alloc-Glu(y-OAllyl)- ()] [ (0.849 g, 3.13 mmol, 100 % yield). ESI-MS: Ci.d I rN aO·. (M+Na) 294 1; found 294.1. (2039) [01195] To the Alloc-Glu(y-OAllyl)-OH intermediate (0.7 g, 2.58 mmol) was added H- Val-G/~Bu (HC1 salt) (0.541 g, 2.58 mmol), HOAt (0.369 g, 2.71 mmol), DMF (12.90 mL) and triethylamine (1.079 mL, 7.74 mmol). The resulting solution was stirred at 0 C for 10 min, and then HATU (1.276 g, 3.35 mmol) was added and the reaction mixture was allowed to warm to room temperature and stirred for 12 hours. The crude reaction mixture was partitioned between DCM (100 mL) DCM and half-saturated LCl (100 mL). The aqueous layer was extracted with DCM, and the combined organic layers were washed with brine, dried over Na2S04, and concentrated. The crude product was purified on silica gel (0-100% EtOAc in hexanes) to afford the intermediate compound 42-Q/-Bu (0.4942 g, 44.9 % yield). ESI-MS: calc for CiiFLs^CU (M+H) 427.2; found 427.1. (2040) [01196] To the intermediate compound 42-0/~Bu (0.028 g, 0.065 mmol) was added DCM (1.3 mL) and TFA (0.247 mL, 3.25 mmol), and the reaction was stirred at room temperature for 3 hours. The reaction mixture was then concentrated to provide compound 43 (0.024 g, 100 % yield). ESI-MS calc for Ci7H27N207+ (M+H) 371.2; found 371.2 |
Tags: 135544-68-2 synthesis path| 135544-68-2 SDS| 135544-68-2 COA| 135544-68-2 purity| 135544-68-2 application| 135544-68-2 NMR| 135544-68-2 COA| 135544-68-2 structure
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 :