Structure of 118994-89-1
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CAS No. : | 118994-89-1 |
Formula : | C6H7NO3 |
M.W : | 141.12 |
SMILES Code : | O=C(C1=CN=CO1)OCC |
MDL No. : | MFCD04114930 |
InChI Key : | KRMORCCAHXFIHF-UHFFFAOYSA-N |
Pubchem ID : | 10964603 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 32.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.94 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.45 |
Solubility | 5.03 mg/ml ; 0.0357 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.57 |
Solubility | 3.77 mg/ml ; 0.0267 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.69 |
Solubility | 2.86 mg/ml ; 0.0203 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.53 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.09 |
* 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 |
---|---|---|
86% | With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.5 h; | A solution of 33 (29.13 g, 0.207 mol) in THF (206 mL) was added dropwise to a suspension of LiAlH4 (7.85 g, 0.207 mmol) in THF (206 mL) at 0 °C. The reaction mixture was stirred for 30 min at 0 °C (at this point TLC indicated consumption of the SM) and quenched by successive addition of water (8 mL), 10percent NaOH (8 mL) solution, and water (24 mL). The temperature should not exceed 0 °C). The precipitate was filtered and washed several times with THF. The filtrate was evaporated to give 34, which was used without purification. M = 17.7 g. Yield = 86percent. |
70% | With sodium tetrahydroborate In ethanol at 0 - 20℃; | Example A.8 Ethyl oxazole-5-carboxylate (1 g, 7.09 mmol, 1 eq) was dissolved in EtOH(l4mL) and the mixture was cooled to 0°C. Sodium borohydride (0.54 g, 14.1 7mmol, 2eq) was added portionwise while stirring, and then the mixture was allowed to warm to r.t.. After overnight stirring at r.t. the conversion was complete by TLC (95/5 DCM/MeOH). The mixture was cooled to 0°C and 2N HC1 was added dropwise till gas evolution ceased (pH 5-6). The obtained suspension was concentrated at reducedpressure, and the residue was purified by flash chromatography (5i02) using as eluent a mixture DCM/MeOH = 95/5. The pure intermediate (11) were obtained as colourless oil (0.49 g, yield 70percent). |
58% | With sodium tetrahydroborate In ethanol at 0 - 20℃; for 16 h; Inert atmosphere | [000282] Synthesis of oxazol-5-ylmethanol (343): To a stirred solution of ethyl oxazole-5- carboxylate 342 (2 g, 14.18 mmol) in EtOH (20 mL) under argon atmosphere was added sodium borohydride (1.07 g, 28.36 mmol) at 0 °C; warmed to RT and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution (25 mL) and extracted with 5percent MeOH/ CH2C12 (2 x 20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 5percent MeOH/ CH2C12 to afford compound 343 (810 mg, 58percent) as colorless syrup. TLC: 5percent MeOH/ CH2C12 (R 0.3); 1H-NMR (DMSO-d6, 500 MHz): ö 8.28 (s, 1H), 7.04 (s, 1H), 5.36 (t, J 6.0 Hz, 1H), 4.47 (d, J 6.0 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0 - 20℃; for 3h; | INTERMEDIATE 171 - PREPARATION OF ethyl oxazole-5-carboxylate; 1 ,8-Diazabicyclo[5.4.0]undec-7-ene (0.574 ml 3.84 mmol) was added simultaneously with ethyl glyoxalate (50% in toluene, 0.659 ml 3.33 mmol) to a mixture of tosylmethyl isocyanide (0.500 g; 2.560 mmol) in dichloromethane (10 ml.) at 00C. The resulting mixture was stirred at room temperature for 3 hours, diluted in dichloromethane and washed with sodium hydrogen sulphate, sodium carbonate, dried over magnesium sulphate and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 5 to 60 % ethyl acetate in heptane) to yield 0.194 g (54 %) of ethyl oxazole-5-carboxylate as a colorless oil.ESI/APCI(+): 142(M+H). |
51% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0 - 20℃; for 8h; | To a stirred solution of TosMIC (50.0?g, 256?mmol) in CH2Cl2 (255?mL) was added ethyl glyoxylate (~50% in toluene, 56?mL, 283?mmol, 1.1 equiv). The solution was cooled to 0?C, and at this temperature, DBU (38?mL, 254?mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 8?h. The reaction mixture was washed with water (~300?mL), organic layers was dried over Na2SO4 and evaporated. The residue was distilled at reduced pressure. bp?=?98?C (25?mbar). M?=?18.3?g. Yield?=?51%. 1H NMR: (CDCl3, 400?MHz) delta?=?1.35 (t, J?=?7.2?Hz, 3?H), 4.35 (q, J?=?7.1?Hz, 2?H), 7.73 (s, 1?H), 7.99 (s, 1?H). 13C NMR (CDCl3, 100?MHz): delta?=?14.2, 61.7, 133.3, 142.9, 153.3, 157.6. |
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0℃; for 1.33333h;Inert atmosphere; | All weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide. Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0 C under N2. In a seperate vessel, ethyl glyoxalate (50 wt% solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C, then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCI (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2S04, then evaporated on Buchi, 25 C, 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C, vapour temperature 60-80 C to afford ethyl oxazole-5-carboxylate as a colourless oil. |
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0℃; for 1.33333h;Inert atmosphere; | All weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide.Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0 C. under N2. In a seperate vessel, ethyl glyoxalate (50 wt % solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C., then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCl (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2SO4, then evaporated on Buchi, 25 C., 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C., vapour temperature 60-80 C. to afford ethyl oxazole-5-carboxylate as a colourless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 0.5h; | A solution of 33 (29.13?g, 0.207?mol) in THF (206?mL) was added dropwise to a suspension of LiAlH4 (7.85?g, 0.207?mmol) in THF (206?mL) at 0?C. The reaction mixture was stirred for 30?min?at 0?C (at this point TLC indicated consumption of the SM) and quenched by successive addition of water (8?mL), 10% NaOH (8?mL) solution, and water (24?mL). The temperature should not exceed 0?C). The precipitate was filtered and washed several times with THF. The filtrate was evaporated to give 34, which was used without purification. M?=?17.7?g. Yield?=?86%. |
70% | With sodium tetrahydroborate; In ethanol; at 0 - 20℃; | Example A.8 Ethyl oxazole-5-carboxylate (1 g, 7.09 mmol, 1 eq) was dissolved in EtOH(l4mL) and the mixture was cooled to 0C. Sodium borohydride (0.54 g, 14.1 7mmol, 2eq) was added portionwise while stirring, and then the mixture was allowed to warm to r.t.. After overnight stirring at r.t. the conversion was complete by TLC (95/5 DCM/MeOH). The mixture was cooled to 0C and 2N HC1 was added dropwise till gas evolution ceased (pH 5-6). The obtained suspension was concentrated at reducedpressure, and the residue was purified by flash chromatography (5i02) using as eluent a mixture DCM/MeOH = 95/5. The pure intermediate (11) were obtained as colourless oil (0.49 g, yield 70%). |
64% | With sodium tetrahydroborate; In tetrahydrofuran; at 0 - 25℃; for 49h; | Step 7: Preparation of oxazol-5-ylmethanol. [0747] To a solution of <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (2.00 g, 14.2 mmol) in THF (20 mL) was added NaBTU (1.07 g, 28.3 mmol) at 0 C and then the mixture was stirred at 25 C for 48 h. A white cloudy was formed. To the mixture was added anhydrous Na2S04 (20 g) and the mixture was stirred at 25 C for 1 hour. The mixture was filtered and the cake was washed with MTBE (20 mL). The combined organic layer was concentrated to dryness. The residue was purified by Combi Flash (EtOAc in pentane from 10% to 100%) to give oxazol-5-ylmethanol (900 mg, 64% yield) as colorless oil. NMR (400 MHz, CDCb) d 2.02 (1H, brt, J= 6.0 Hz), 4.74 (2H, d, J= 6.0 Hz), 7.06 (1H, s), 7.89 (1H, s). |
58% | With sodium tetrahydroborate; In ethanol; at 0 - 20℃; for 16h;Inert atmosphere; | [000282] Synthesis of oxazol-5-ylmethanol (343): To a stirred solution of ethyl oxazole-5- carboxylate 342 (2 g, 14.18 mmol) in EtOH (20 mL) under argon atmosphere was added sodium borohydride (1.07 g, 28.36 mmol) at 0 C; warmed to RT and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution (25 mL) and extracted with 5% MeOH/ CH2C12 (2 x 20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 5% MeOH/ CH2C12 to afford compound 343 (810 mg, 58%) as colorless syrup. TLC: 5% MeOH/ CH2C12 (R 0.3); 1H-NMR (DMSO-d6, 500 MHz): oe 8.28 (s, 1H), 7.04 (s, 1H), 5.36 (t, J 6.0 Hz, 1H), 4.47 (d, J 6.0 Hz, 2H). |
With sodium tetrahydroborate; ethanol; calcium chloride; In tetrahydrofuran; at 0℃; | At 0 under ice-cooling, the solution containing oxazole-5-carboxylate (3.57g, 25.0mmol) in 50mL of ethanol and 50mL of THF was added anhydrous CaCl2(11.1g, 100.0mmol), and stirred until the solid completely dissolved, then the solution was added portionwise NaBH4(2.70g, 71.0mmol).The reaction overnight, the reaction end point detection LCMS, after completion of the reaction, the mixed solution was added saturated NH4Cl solution, and extracted three times of dichloromethane was added 30mL liquid separation, the organic phases combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to dryness to give a crude product 1.98g of 5-hydroxymethyl isoxazole, a yield of 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of ethyl 1 ,3-oxazole-5-carboxylate (0.86 g, 6.07 mmol) in THF (12,2 mL) at -40 0C were added potassium hexamethyldisilylazide (0.5 M; 14.6 niL, 7.29 mmol). After 1 h, a solution of iodine (3.85 g, 15.2 mmol) in THF (8 mL) was slowly added over 15 min. The mixture was stirred at -40 0C for 1 h then allowed to warm to ambient temperature. Sat. NaHCtheta3 and sat. Na2SC^ were added and the mixture was extracted with dchloromethane (3x). The combined organic extracts was dried over MgSO4, filtered and concentrated. Purification by silica gel chromatography (100% hexanes - » 90 % hexanes/ ethyl acetate) gave the title compound (0.86 g, 32% pure). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With bromine; lithium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at -60℃; for 4h; | To a solution of <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (0.28 g, 2.00 mmol) in THF/DMF (2/2 mL) was added Br2 (0.13 mL, 2.6 mmol, 1.3 eq.) and LHMDS (2.6 mL 2.6 mmol, 1.3 eq) to obtain a reaction mixture, which was stirred at -60 C. for 4 hours. The reaction mixture was extracted with EA and water and the combined organic layer was dried with MgSO4. The residue was purified by flash chromatography with EA/Hex (EA/Hex=1:4) to give OS-a.1 as yellow oil (0.1 g, 30%). |
4-bromo<strong>[118994-89-1]oxazole-5-carboxylic acid ethyl ester</strong>To a solution of <strong>[118994-89-1]oxazole-5-carboxylic acid ethyl ester</strong> (12.2 g) in a mixture of tetrahydrofuran (70 ml.) and 1 ,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (70 ml.) was added, over 30 minutes at -65 to -78C under nitrogen, a 1.0 M solution of 1 ,1 ,1 ,3,3,3-hexamethyldisilazane lithium salt in tetrahydrofuran (110 ml_). The solution was stirred at -780C for 80 minutes, then bromine (5.8 ml_) was added dropwise over 20 minutes and the resulting mixture was stirred at -780C for a further 45 minutes. The cold solution was added to a mixture of te/t-butylmethyl ether (50O mL) and 10% aqueous sodium thiosulfate solution (500 ml_) at room temperature. The phases were separated and the organic layer was washed with water and brine, then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of diethyl ether and pentane (0:1 to 1 :1 by volume), to afford the title compound (2.44 g) as a solid mass.MS: ESI (+ve) (Method E): 220 (M+H)+, Retention time 3.27 min. | ||
With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; bromine; | Ethyl 4-bromooxazole-5-carboxylate (2) To a solution of <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1) (100.0 g, 0.71 mol) in THF (500 mL) and DMPU (500 mL) was added LiHMDS (1.0 M, 921 mL, 921 mmol) dropwise at -78 C. under N2 atmosphere, and the mixture was stirred for 1.5 hours. Then Br2 (54.5 mL, 1.06 mol) was added dropwise at the same temperature and the resulting mixture was stirred for 0.5 hours. TLC showed the starting material disappeared. The resulting solution was poured into a room temperature saturated aqueous NH4Cl (1000 mL), extracted with EtOAc (500 mL*3). The combined organic layers were washed with brine (500 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by MPLC to give ethyl 4-bromooxazole-5-carboxylate (25.0 g, purity: 90%, yield: 11%) as yellow oil. 1H NMR (400 MHz, CHCl3-d): delta 7.94 (s, 1H), 4.43 (q, J=7.3 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | LiHMDS (1M solution, 15 mL, 15.0 mmol) was added at -78 C to a solution of <strong>[118994-89-1]ethyl 5-oxazolecarboxylate</strong> [118994-89-1] (1.26 mL, 10.0 mmol) in THF (50 mL). The reaction mixture was stirred at -78 C for 1 h and ZnCl2 (0.7M solution, 22.8 mL, 16.0 mmol) was added drop wise. The reaction mixture was warmed to room temperature and stirred for 30 min. A solution of I2 (5.13 g, 20.0 mmol) in THF (5 mL) was added drop wise at -78 C. The reaction mixture was stirred at -78 C for 15 min and at room temperature for 1 h. The mixture was diluted with Na2S203 (sat., aq.) and extracted with Et20 (twice). The combined organic extracts were dried (MgS04), filtered and concentrated in vacuo. The crude mixture was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 95:5) to afford 1-159 (2.2 g, 82%). | |
42% | To a solution of 1 ,3-oxazole-5-carboxylate (1.02 g, 7.17 mmol) in THF (25 ml.) at - 78 0C was added LHMDS (7.53 ml_, 7.53 mmol). After 1 hour, a solution of diiodoethane (1.04 ml_, 7.88 mmol) in THF (10 ml.) was added over 15 minutes. The mixture was stirred for an additional 1 hr at -78 0C and warmed to room temperature. The mixture was poured onto cold Et2O (200 ml.) and 10% Na2S2O3 (200 ml_). The organic layer was separated, dried over Na2SO4 and purified via column chromatography (silica, 0 - 40% EtOAc/hexanes) affording the product as a white solid (805 mg, 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Method DAll weights, volumes and equivalents are relative to 6-chloro-4-iodo-1-(phenylsulfonyl)-1 H- indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) in tetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for 92 wt% assay) in tetrahydrofuran (5 vols, 225 ml) is added to the vessel. The suspension is cooled to -10 C (+/-5 C) under a nitrogen atmosphere and a 1 M solution of bis- (trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30 vols, 193 ml) is added over 15 minutes maintaining the temperature at -10 C (+/-5 C). The resulting solution is stirred under a nitrogen atmosphere at -10 C (+/-5 C) for 1 hour. To the solution is added 6-chloro-4-iodo-1-(phenylsulfonyl)-1 H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (the mixture is degassed with vacuum/nitrogen 3 times) and then heated to 60C (+/-3C) for at least 6 hours. The reaction is then checked by HPLC for completion. The reaction solution is cooled to 0 C (+/-3 C) and a solution of 25% w/w diisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288 ml) is added maintaining the temperature at <5C. The resulting reaction solution is then stirred at 0C (+/-3C) for at least 1 hour. The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise to a solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C (+/-5 C) over ~1 h. The resulting solution is stirred at 20 C for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2 x 3 vols, 2 x 135 ml) and filtered through a porosity 4 sinter. The organic layer is then evaporated under reduced pressure (45 C, 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C, 50 mbar) to remove all traces of other solvents. To the solution at 45 C is added water (5 vols, 225 ml) dropwise over 30 minutes, the resulting reaction mixture is cooled to 20 C over 3hr and stirred at 20 C for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1 :2) (2 vols, 90 ml), then washed with water (3 vols, 135 ml), then dried under high vacuum at 60 C (+/-3 C) to constant probe temperature to afford (2-(6-chloro-1- (phenylsulfonyl)-1 H-indazol-4-yl)oxazol-5-yl)methanol as a beige solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0℃;Inert atmosphere; | 8Ethyl oxazole-5-carboxylateAll weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide.Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61 .6 ml, 5 vols) at 0 C under N2. In a seperate vessel, ethyl glyoxalate (50 wt% solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61 .6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C, then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCI (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2S04, then evaporated on Buchi, 25 C, 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C, vapour temperature 60-80 C to afford ethyl oxazole-5-carboxylate as a colourless oil. | |
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; toluene; at 0℃; for 1.33333h;Inert atmosphere; | Ethyl oxazole-5-carboxylate All weights, volumes and equivalents are relative to toluenesulfonylmethyl isocyanide. Toluenesulfonylmethyl isocyanide (TosMIc) (12.31 g, 1 wt, 1 eq) is dissolved in DCM (61.6 ml, 5 vols) at 0 C. under N2. In a separate vessel, ethyl glyoxalate (50 wt % solution in toluene, 20.6 g, 20.0 ml, 1.67 wt) is diluted with DCM (61.6 ml, 5 vols) under N2 and DBU (12.48 g, 12.35 ml, 1.3 eq, 1.01 wt) is added resulting in a purple solution. The second solution is added to the TosMIc solution over 1 hr, maintaining temperature at 0 C., then checked by HPLC for completion after a further 20 mins. The reaction is quenched by slow addition of 2M HCl (10 vols, 123 ml) and the DCM layer separated. The aqueous layer is re-extracted with DCM (5 vols, 61.6 ml), and the combined organics dried over Na2SO4, then evaporated on Buchi, 25 C., 100 mbar to remove DCM and toluene. Distilled at 12 mbar, jacket temperature 105 C., vapour temperature 60-80 C. to afford ethyl oxazole-5-carboxylate as a colourless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In methanol; ammonia;liquid NH3; | Step A: Oxazole-5-carboxamide Ethyl oxazole-5-carboxylate (2 g, 14.2 mmol) was dissolved in NH3 solution (7 M in MeOH, 25 mL). The solution was stirred at room temperature for 2 hr and filtered. The solid was dried to give the desired product (1.5 g, 92% yield) as a white powder which was used directly in the next step. |
92% | With ammonia; In methanol; at 20℃; for 2h; | Example 17. Preparation of (S)-N-((S)-l-(2-chlorophenyl)-2-((3,3- difluorocyclobutyl)amino)-2-oxoethyl)-l-(5-cyanooxa-zol-2-yl)-N-(3,5-difluorophenyl)-5- oxopyrrolidine-2-carboxamide (sin le enantiomer) - Compound 162 Step A : Oxazole-5-carboxamide. Ethyl oxazole-5-carboxylate (2 g, 14.2 mmol) was dissolved in NH3 solution (7 M in MeOH, 25 mL). The solution was stirred at room temperature for 2 hr and filtered. The solid was dried to give the desired product (1.5 g, 92% yield) as a white powder which was used directly in the next step. |
92% | In ammonia;liquid NH3; | Step A: Oxazole-5-carboxamide Ethyl oxazole-5-carboxylate (2 g, 14.2 mmol) was dissolved in NH3 solution (7 M in MeOH, 25 mL). The solution was stirred at room temperature for 2 hr and filtered. The solid was dried to give the desired product (1.5 g, 92% yield) as a white powder which was used directly in the next step. |
92% | With ammonia; In methanol; at 20℃; for 2h; | Ethyl oxazole-5-carboxylate (2 g, 14.2 mmol) was dissolved in NH3 solution (7M in MeOH, 25 mL). The solution was stirred at room temperature for 2hr and filtered. The solid was dried to give the desired product (1.5 g, 92% yield) as a whitepowder which was used directly in the next step. |
92% | With ammonia; In methanol; at 20℃; for 2h; | Step A .- Oxazole-5-carboxamide. Ethyl oxazole-5-carboxylate (2 g, 14.2 mmol) was dissolved in NH3 solution (7 M in MeOH, 25 mL). The solution was stirred at room temperature for 2 hr and filtered. The solid was dried to give the desired product ( 1 .5 g, 92% yield) as a white powder which was used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
All weights, volumes and equivalents are relative to 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) in tetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for 92 wt % assay) in tetrahydrofuran (5 vols, 225 ml) is added to the vessel. The suspension is cooled to -10 C. (+/-5 C.) under a nitrogen atmosphere and a 1M solution of bis-(trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30 vols, 193 ml) is added over 15 minutes maintaining the temperature at -10 C. (+/-5 C.). The resulting solution is stirred under a nitrogen atmosphere at -10 C. (+/-5 C.) for 1 hour. To the solution is added 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (the mixture is degassed with vacuum/nitrogen 3 times) and then heated to 60 C. (+/-3 C.) for at least 6 hours. The reaction is then checked by HPLC for completion. The reaction solution is cooled to 0 C. (+/-3 C.) and a solution of 25% w/w diisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288 ml) is added maintaining the temperature at . The resulting reaction solution is then stirred at 0 C. (+/-3 C.) for at least 1 hour. The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise to a solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C. (+/-5 C.) over 1 h. The resulting solution is stirred at 20 C. for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2×3 vols, 2×135 ml) and filtered through a porosity 4 sinter. The organic layer is then evaporated under reduced pressure (45 C., 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C., 50 mbar) to remove all traces of other solvents. To the solution at 45 C. is added water (5 vols, 225 ml) dropwise over 30 minutes, the resulting reaction mixture is cooled to 20 C. over 3 hr and stirred at 20 C. for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1:2) (2 vols, 90 ml), then washed with water (3 vols, 135 ml), then dried under high vacuum at 60 C. (±3 C.) to constant probe temperature to afford (2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazol-5-yl)methanol as a beige solid. | ||
All weights, volumes and equivalents are relative to6-chioro-4-iodo-1 -(phenylsulfonyl)-1 H-indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) intetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for92 wt % assay) in tetrahydroffiran (5 vols, 225 ml) is added tothe vessel. The suspension is cooled to -10 C. (+1-5 C.) under a nitrogen atmosphere and a 1M solution of bis-(trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30vols, 193 ml) is added over 15 minutes maintaining the temperature at - 10C. (+ 1-5C.). The resulting solution is stirredunder a nitrogen atmosphere at -10 C. (+1-5 C.) for 1 hour. To the solution is added 6-chioro-4-iodo-1 -(phenylsulfonyl)1H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (themixture is degassed with vacuumlnitrogen 3 times) and then heated to 60 C. (+ 1-3 C.) for at least 6 hours. The reactionis then checked by HPLC for completion. The reaction solution is cooled to 0 C. (+1-3 C.) and a solution of 25% wlwdiisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288ml) is added maintaining the temperature at <5 C. The resulting reaction solution is then stirred at 0 C. (+1-3 C.) for atleast 1 hout The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise toa solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C. (+1-5 C.) over 1 h. The resulting solutionis stirred at 20 C. for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2x3vols, 2x135 ml) and filtered through a porosity 4 sintet The organic layer is then evaporated under reduced pressure (45C., 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C., 50 mbar) to remove all traces ofother solvents. To the solution at 45 C. is added water (5 vols,225 ml) dropwise over 30 minutes, the resulting reactionmixture is cooled to 20 C. over 3 hr and stirred at 20 C. for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1:2) (2 vols, 90 ml), thenwashed with water (3 vols, 135 ml), then dried under highvacuum at 60 C. (±3 C.) to constant probe temperature toafford (2-(6-chloro- 1 -(phenylsulfonyl)- 1 H-indazol-4-yl)ox- azol-5-yl)methanol as a beige solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 1-Adamantanecarboxylic acid; palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 8h;Inert atmosphere; | j0238] Procedure:10239] Pd(OAc)2 (31.8 mg, 0.14 mmoles), [P(t-13u)3H] HF4 (123.2 mg, 0.42 mmoles), 1-adamantanecarboxylic acid (153 mg, 0.85 mmoles), K2C03 (782 mg, 5.7 mmoles), and methyl 6-bromonicotinate (918mg, 4.3 mmoles) were added to a dried flask. The flask was fitted with a reflux condenser capped with a septum, evacuated, and purged with nitrogen (.-5 times). A degassed solution of ethyl oxazole-5-carboxy- late (400 mg, 2.8 mmoles) in dry toluene (7 mE) was added via syringe, and the reaction was stirred at 1100 C. for 8 h. The reaction mixture was cooled and filtered through Celite, and the filtrate was concentrated under reduced pressure. The crude product was then purified by chromatography on silica (30% EtOAc in hexanes followed by 2% acetone in 1:1 DCM:hexanes) to afford the title compound (183 mg, 23%) as a white solid. ?H NMR (400 MHz, CDC13) oe 9.37 (dd, J=0.8, 2.0 Hz, 1H), 8.47 (dd, J=2.0, 8.0 Hz, 1H), 8.30 (dd, J=0.8, 8 Hz, 1H), 7.96 (s, 1H), 4.46 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ?3C NMR (100 MHz, CDC13) oe 164.9, 161.6, 157.5, 151.5, 148.0, 143.8, 138.3, 135.5, 127.3, 122.5, 61.9, 52.7, 14.3; HRMS (ESI) mlz 277.0823 [calc?d for C,3H,3N205 (M+H) 279.0819]. For experiments with mammalian cells, this compound was recrystallized from EtOAc to afford a white crystalline solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 3,3-dimethyl-butan-2-one; palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 110℃; for 24h;Inert atmosphere; | j0241] Procedure:j0242] Pd(OAc)2 (15.9 mg, 0.071 mmoles), [P(t-Hu)3H] HF4 (61.8 mg, 0.21 mmoles), pivalic acid (29.0 mg, 0.28 mmoles), K2C03 (391 mg, 2.8 mmoles), ethyl oxazole-4- carboxylate (200 mg, 1.4 mmoles), and methyl 6-bromoni- cotinate (612 mg, 2.8 mmoles) were added to a dried flask. The flask was fitted with a reflux condenser capped with a septum, evacuated, and purged with nitrogen (.-5 times). Drytoluene (7 mE) was added via syringe, and the reaction was stirred at 1100 C. for 24 h. The reaction mixture was cooled and filtered through Celite, and the filtrate was concentrated under reduced pressure. The crude product was then purified via chromatography on silica (2% acetone in DCM followed by 10% acetone 1:1 DCM:hexanes) to afford the title compound (113 mg, 29%) as a white solid. ?H NMR (400 MHz, CDC13) oe 9.31 (dd, J=0.8, 2.0 Hz, 1H), 8.46 (dd, J=2.0, 8.4 Hz, 1H), 8.42 (s, 1H), 8.38 (dd, J=0.8, 8.4 Hz, 1H), 4.45 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ?3C NMR (100 MHz, CDC13) oe 164.9, 160.8, 160.2,151.1, 148.0, 145.2, 138.3, 135.3, 127.1, 122.3, 61.6, 52.7, 14.3; HRMS (ESI) mlz 277.0815 [calc?d for C,3H,3N205 (M+H) 277.0823]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.5% | With lithium hydroxide monohydrate; water; at 25℃; for 6.5h;Large scale; | An aqueous solution of lithium hydroxide monohydrate (124.5 kg of a solution preparedfrom 49.44 kg lithium hydroxide monohydrate dissolved in 319 kg water, 398 mol) was added to asolution of <strong>[118994-89-1]ethyl 5-oxazolecarboxylate</strong> (54 kg, 382.7 mol) in water (54 kg) maintaining the temperature below 25 C. The reaction was stirred for 6.5 h and then conc. aqueous HCI (64.8 kg) was added maintaining the temperature below 25 C, the crystallisation cooled to 5 C and held forh. The product was filtered off, washed with cold water (88 kg), then isopropanol (171 kg) anddried under vacuum at 50 C to give the title compound (37.88 kg, 87.S%).1H NMR (400 MHz, DMSO-d6) ppm 13.68 (br. 5., 1 H), 8.59 (5, 1 H), and 7.88 (5, 1 H). |
87.5% | With lithium hydroxide monohydrate; In water; at 25℃; for 6.5h;Large scale; | An aqueous solution of lithium hydroxide monohydrate (124.5 kg of a solution prepared from 49.44 kg lithium hydroxide monohydrate dissolved in 319 kg water, 398 mol) was added to a solution of <strong>[118994-89-1]ethyl 5-oxazolecarboxylate</strong> (54 kg, 382.7 mol) in water (54 kg) maintaining the temperature below 25 C. The reaction was stirred for 6.5 h and then cone, aqueous HCI (64.8 kg) was added maintaining the temperature below 25 C, the crystallisation cooled to 5 C and held for 1 h. The product was filtered off, washed with cold water (88 kg), then isopropanol (171 kg) and dried under vacuum at 50 C to give the title compound (37.88 kg, 87.5%). (0437) *H NMR (400 MHz, DMSO-cfe) delta ppm 13.68 (br. s., 1 H), 8.59 (s, 1 H), and 7.88 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | 1-Isopropylpiperazine (1.06 g, 8.24 mmol) and ethyl-oxazole-5-carboxylate (1.16 g, 8.24 mmol) were added to a suspension of 5 A molecular sieves (8.0 g) in cyclopentyl methyl ether (40 mL) and stirred for 1 h at 55 C. Lyophilised lipase TL (2.0 g) was added, the reaction mixture stirred for 28.75 h, then filtered through glass fibre paper, washed through with cyclopentyl methyl esther (3 x6 mL). The combined filtrate and washings were concentrated under reduced pressure and the crude residue re-slurried in methyl cyclohexane (6 mL), filtered off, washed with methyl cyclohexane (2 x 5 mL), and dried under vacuum to give the title compound (1.40 g, 76%). | |
76% | 1-Isopropylpiperazine (1.06 g, 8.24 mmol) and ethyl-oxazole-5-carboxylate (1.16 g, 8.24 mmol) were added to a suspension of 5 A molecular sieves (8.0 g) in cyclopentyl methyl ether (40 mL) and stirred for 1 h at 55 C. Lyophilised lipase TL (2.0 g) was added, the reaction mixture stirred for 28.75 h, then filtered through glass fibre paper, washed through with cyclopentyl methyl ether (3 x 6 mL). The combined filtrate and washings were concentrated under reduced pressure and the crude residue re-slurried in methyl cyclohexane (6 mL), filtered off, washed with methyl cyclohexane (2 x 5 mL), and dried under vacuum to give the title compound (1.40 g, 76%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With selenium; potassium phosphate; copper(l) chloride; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; | In room temperature, 2,4,6-trimethyliodobenzene (12 mmol, 3 equiv), elemental selenium (12 mmol, 3 equiv), ethyl 1,3-oxazol-5-carboxylate (4 mmol, 1 equiv), copper chloride (0.4 mmol) and potassium phosphate (12 mmol, 3 equiv) were added to the reaction tube, then filled with nitrogen, and replaced three times. In a nitrogen reaction environment, then 20 mL of N,N-dimethylformamide reaction solvent was added. Stir at a reaction temperature of 140 C for 24 h. After monitoring the reaction by thin layer chromatography, the reaction mixture was cooled. Then, ethyl acetate was added for dilution, and the diluted solution was transferred to a separatory funnel and extracted with saturated brine. The aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, 25 g of anhydrous sodium sulfate was added, and the mixture was stood still for 30 min. Wash the filter cake 3 times with 50 mL of ethyl acetate each time. Then spin off the solvent, the product was isolated by column chromatography (eluent: petroleum ether: diethyl ether = 98:2), yield 77%, product weight: 1.044 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Under a argon atmosphere, tetrahydrofuran (500 mL) was added to the reaction flask andCompound 1 is <strong>[118994-89-1]oxazole-5-carboxylic acid ethyl ester</strong> (32 g 0.23 mol 1 eq). The temperature was lowered to -70 to -80 C, and then LiHMDS (250 ml, 0.25 mol, 1.1 eq.) was slowly added dropwise.After the dropwise addition, the temperature was kept at -70 to -80 C, and the reaction was stirred for 10 minutes.CBr4 (106 g, 0.32 mol, 1.4 eq.) was added in portions, and after the addition, the temperature was kept at -70 to -80 C, and the reaction was stirred for 2 hours.After extraction with saturated ammonium chloride, it was slowly warmed to room temperature.Extract with ethyl acetate (250 mL * 2), wash with water (250 mL * 2), and wash with saturated brine (250 mL * 1).Concentrated and mixed with the column to obtain 34.4 g of product, the yield was 68%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.2 g | With tri-tert-butyl phosphine; palladium diacetate; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere; | To a stirred suspension of 2-bromopyridine (450 mg, 0.005 mol, leq) <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (450 mg, 2.86 mmol, leq), CS2CO3 (2.82gm, 8.59 mmol, 3 eq), dioxane (10 mL) and water (2 mL) was purged with nitrogen for 5 minutes. P(t-Bu)3 (12.87 mg, 0.057. mmol, 0.2 eq) and Pd(OAc)2 (12.873 mg, 0.057 mmol, 0.2 eq) was added to the reaction mixture, which was heated to 80 C for 2 hours. The cooled reaction mixture was diluted with water, Extracted with EtOAc. The combined EtOAc extracts was washed with water, dried over NaSCE. filtered through pad of silica gel and concentrated. The residue was chromatographed on silica gel plug eluting with 5-40% EtO Ac/hexanes to give tert-butyl 3-(2-chloropyrimidin-4- yl)-2-methyl- 1E1 -indole- l-carboxylate (0.2 gm). LCMS: 220 [M+H] +. |
Tags: 118994-89-1 synthesis path| 118994-89-1 SDS| 118994-89-1 COA| 118994-89-1 purity| 118994-89-1 application| 118994-89-1 NMR| 118994-89-1 COA| 118994-89-1 structure
A190443 [651059-70-0]
Methyl 2-methyloxazole-5-carboxylate
Similarity: 0.87
A174171 [1257266-93-5]
Ethyl 2-vinyloxazole-5-carboxylate
Similarity: 0.84
A135089 [113853-16-0]
Ethyl 2-aminooxazole-5-carboxylate
Similarity: 0.83
A193729 [862599-47-1]
Ethyl 2-chlorooxazole-5-carboxylate
Similarity: 0.81
A190443 [651059-70-0]
Methyl 2-methyloxazole-5-carboxylate
Similarity: 0.87
A145160 [1216012-87-1]
2-Methyloxazole-5-carboxylic acid
Similarity: 0.85
A174171 [1257266-93-5]
Ethyl 2-vinyloxazole-5-carboxylate
Similarity: 0.84
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P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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