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CAS No. : | 2446-83-5 | MDL No. : | MFCD00008875 |
Formula : | C8H14N2O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 202.21 | Pubchem ID : | - |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 6 |
Num. H-bond acceptors : | 6.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 48.77 |
TPSA : | 77.32 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.72 cm/s |
Log Po/w (iLOGP) : | 2.9 |
Log Po/w (XLOGP3) : | 2.55 |
Log Po/w (WLOGP) : | 2.53 |
Log Po/w (MLOGP) : | 1.63 |
Log Po/w (SILICOS-IT) : | 1.19 |
Consensus Log Po/w : | 2.16 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.3 |
Solubility : | 1.0 mg/ml ; 0.00496 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.82 |
Solubility : | 0.0305 mg/ml ; 0.000151 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.01 |
Solubility : | 19.9 mg/ml ; 0.0984 mol/l |
Class : | Soluble |
PAINS : | 1.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.85 |
Signal Word: | Danger | Class: | 9 |
Precautionary Statements: | P201-P202-P260-P264-P271-P273-P280-P302+P352-P304+P340+P312-P305+P351+P338-P308+P313-P332+P313-P337+P313-P362-P391-P403+P233-P405-P501 | UN#: | 3082 |
Hazard Statements: | H315-H319-H335-H350-H373-H401-H410 | Packing Group: | Ⅲ |
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 |
---|---|---|
77.8% | With pyridine; N-Bromosuccinimide In toluene at 20℃; for 2 h; | To a 30 ml flask, hydrazine hydrate (200 mg, 4.0 mmol),Tetrahydrofuran (10 ml)And sodium carbonate (551 mg, 5.2 mmol) were added, and under ice cooling,Chlorocarbonic acid isopropyl ester (980 mg, 8.0 mmol) was added dropwise, followed by reaction for 1 hour.After completion of the reaction, the solid was removed by filtration, and the obtained filtrate was concentrated to about 90 vol percent of 1,2-hydrazinedicarboxylic acid diisopropyl ester to give tetrahydrofuranToluene (10 ml) was added, and the remaining tetrahydrofuran was removed by concentration to give 1, A toluene solution of 2-hydrazinedicarboxylic acid diisopropyl ester was obtained.Then, pyridine (316.4 mg, 4.0 mmol) was added to a toluene solution of 1,2-hydrazinedicarboxylic acid diisopropyl ester,, And toluene (10 ml) were added, and N-bromosuccinimide (711.9 mg, 4.0 mmol) was slowly added at 20 ° C. and reacted for 2 hours.After completion of the reaction, the solution was washed with water (3 mL × 2 times), dehumidified with anhydrous magnesium sulfate, and concentrated to dryness. The residue was distilled to obtain diisopropyl azodicarboxylate as a clear solution(628.5 mg, yield 77.8percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.8% | With pyridine; N-Bromosuccinimide; In toluene; at 20℃; for 2h; | To a 30 ml flask, hydrazine hydrate (200 mg, 4.0 mmol),Tetrahydrofuran (10 ml)And sodium carbonate (551 mg, 5.2 mmol) were added, and under ice cooling,Chlorocarbonic acid isopropyl ester (980 mg, 8.0 mmol) was added dropwise, followed by reaction for 1 hour.After completion of the reaction, the solid was removed by filtration, and the obtained filtrate was concentrated to about 90 vol% of 1,2-hydrazinedicarboxylic acid diisopropyl ester to give tetrahydrofuranToluene (10 ml) was added, and the remaining tetrahydrofuran was removed by concentration to give 1, A toluene solution of 2-hydrazinedicarboxylic acid diisopropyl ester was obtained.Then, pyridine (316.4 mg, 4.0 mmol) was added to a toluene solution of 1,2-hydrazinedicarboxylic acid diisopropyl ester,, And toluene (10 ml) were added, and N-bromosuccinimide (711.9 mg, 4.0 mmol) was slowly added at 20 C. and reacted for 2 hours.After completion of the reaction, the solution was washed with water (3 mL × 2 times), dehumidified with anhydrous magnesium sulfate, and concentrated to dryness. The residue was distilled to obtain diisopropyl azodicarboxylate as a clear solution(628.5 mg, yield 77.8%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 72h; | To a stirred solution of (2S, 4R)-4-hydroxy-pyrrolidine-1, 2-dicarboxylic acid 1-tert- butyl ester 2-methyl ester (CAS Reg. No. 74844-91-0) (0.3g, 1. 22mmol), 3-chlorophenol (0. 189g, 1. 47MMOL) and triphenylphosphine (0. 385G, 1. 47MMOL) in THF (2ml) cooled at 0C under N2 was added dropwise the diisopropylazodicarboxylate (0. 29ml, 1. 47MMOL). The mixture was stirred for 3 days at room temperature. The solvent was removed in vacuo and the product was purified by chromatography on silica gel using ether/n- pentane: 40/60 as eluent to afford 0. 27G (62%) of a mixture of the title compound and reduced diisopropyl AZODICARBOXYLATE (1/1) as an oil. 'H NMR (400MHZ, CDC13) : 8 = 1.46, 1.49 (2 x s, 9H), 2.47 (2H, m), 3.71 (5H, m), 4.42 (1H, m), 4.42, 4.54 (1H, 2 x m), 4.87 (1H, m), 6.68 (1H, m), 6.79 (1H, s), 6.92 (1H, m), 7.18 (1H, m). LRMS (ELECTROSPRAY) : m/z 378 (MNa+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine on polystyrene; In tetrahydrofuran; at 0℃; for 0.5h; | Methyl 3-[(1S)-2-methoxy-(1-methylethyl)oxy]-5-[phenylmethyl]oxy}benzoic; To a solution of methyl 3-hydroxy-5-[phenylmethyl] oxy} benzoate (77.4 mmol) in THF was added polymer-supported triphenylphosphine (51.7g of 3 mmol/g loading, 155 mmol) and (R)- (-)-l-methoxy-2-propanol (102 mmol). The stirred solution was blanketed with argon and cooled in an ice bath. A solution of DIAD (116 mmol) was added dropwise by syringe over 10 minutes. The solution was stirred for 20 minutes and filtered, washing the residue with THF (500 mL). The filtrate and washings were combined, and evaporated to give the desired compound which was used without further purification. 'H NMR 6 (d6-DMSO) : 3.26 (s, 3H), 3.44 (m, 2H), 3.82 (s, 3H), 4.63 (m, 1H), 5.14 (s, 2H), 6.85 (s, 1H), 7.05 (s, 1H), 7.11 (s, 1H), 7.30-7. 47 (m, 5H) The 1H NMR spectrum also contained signals consistent with a small amount of bis (l- methylethyl) hydrazine-1, 2-dicarboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In n-heptane; at -5 - 25℃; for 2.75h; | Preparation of S- (+)-2-hydroxy-4- [3-hydroxy- 3- (5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthyl)- 1-propynyl]benzoic acid from 1-(5, 6, 7, 8-tetrahydro- 5, 5, 8, 8-tetramethyl-2-naphthyl) prop-2-yn-1-ol The compound 1- (5, 6,7, 8-tetrahydro-5, 5,8, 8- tetramethyl-2-naphthyl) prop-2-yn-1-ol (31.0 kg) is placed in contact with lipase PS 30 Amano (6.2 kg) and vinyl acetate (11.0 kg) at a-temperature below 40C, in the presence of heptane (47-litres). The mixture is heated at a temperature of about 36 to 40C for 33 hours with mechanical stirring. The mixture is then cooled to a temperature of about 25/30C. The enzyme in suspension is then filtered from the reaction mixture containing the acetate of desired R configuration and the alcohol of S configuration. The mixture is heated again to 40/50C so as to evaporate to constant volume, by adding heptane, the majority of the solvents and reagents. A mixture of 33 kg of alcohol of S configuration and of acetate of R. configuration dissolved in the heptane is thus obtained. 10 litres of heptane cooled to 0/-5C are added to the solution of S alcohol and R acetate obtained above, and 14.3 kg of tri-n-butylphosphine (TBP) are added at a temperature below 25C, in the presence of 4.22 kg of 99% acetic acid at a temperature below 7C. The mixture is cooled to 0/5C, followed by addition of 14.5 kg of <strong>[2446-83-5]diisopropyl azodicarboxylate</strong> (DIAD) at a temperature below 5C. The mixture is then heated-to a temperature of about 20C and maintained at this temperature for 2 hours 45 minutes. The phosphine oxide and the DIAD derivative obtained along with the acetate of desired configuration are removed by liquid-liquid extraction (2 extractions with 5 volumes of methanol/water mixture (85: 15), then 2 back-extractions with 5 volumes of heptane, and then 1'extraction with 5 volumes of methanol/water (85: 15) ). The transesterification of. the R acetate is performed in the presence of sodium carbonate (27.1 kg) and methanol (155 litres), by heating the mixture at 40C for 7 hours 15 minutes. After adding a heptane/water mixture (50: 50), the reaction mixture is again heated to 60/65C to remove. the methanol by distillation. After separation of the organic and aqueous phases,. the crystallization is performed by cooling the organic layer obtained to the point of crystallization and then maintaining it at a temperature below-5C for 30 minutes. After filtration followed by drying for about 11 hours at a maximum temperature of 30C, the R (-) enantiomer of 1- (5, 6,7, 8-tetrahydro-5, 5,8, 8- tetramethyl-2-naphthyl) prop-2-yn-1-ol (18.4 kg) is obtained. The overall chemical yield for the production of this alcohol of R configuration from the racemic mixture is 60% and the chiral purity of the compound is 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triphenylphosphine; In tetrahydrofuran; | EXAMPLE 39 5(R)-Isoxazol-3-yloxymethyl-3-(4-morpholino-3-fluoro-phenyl)oxazolidin-2-one Prepared by the general method of Example 1 using as starting material 5(R)-hydroxymethyl-3-(4-morpholino-3-fluoro-phenyl)oxazolidin-2-one (WO95/07271; 300 mg, 1.01 mmol), 3-hydroxyisoxazole (95 mg, 1.12 mmol), diisopropylazodicarboxylate (225 mg, 1.11 mmol) and triphenylphosphine (305 mg, 1.16 mmol) in THF (5 ml). Purified by flash chromatography (Merck 9385 silica, EtOAc/isohexane (7/3)) to give the title compound (254 mg, 69%) as a colourless solid. 1H-NMR (300 MHz, CDCl3): delta=3.05 (m, 4H), 3.88 (m, 4H), 3.94 (dd, 1H), 4.14 (t, 1H), 4.47-4.62 (m, 2H), 5.01 (m, 1H), 6.00 (d, 1H), 6.94 (t, 1H), 7.15 (dd, 1H), 7.46 (d, 1H), 8.15 (d, 1H). MS: ESP+(M+H)+=364. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; triphenylphosphine; In tetrahydrofuran; | Step 1 Mitsunobo Procedure 1-[2-(4-Methyl-2-nitro-phenoxy)-ethyl]-aziridine. A solution of 2-nitro-4-methylphenol (505 mg, 3.3 mmol, 1.1 eq.) and 2-aziridin-1-yl-ethanol (3.0 mmol, 1 eq.) in 10 mL THF was stirred at 0 C. Triphenylphosphine (0.87 g, 3.30 mmol, 1.1 eq.) and diisopropylazodicarboxylate, (0.67 g 3.30 mmol, 1.1 eq.) were added, and the solution was allowed to warm to temperature. After 18 h, the reaction mixture was diluted with 100 mL EtOAc, and was washed with water (3*20 mL). The organic phase was washed again with 1 N HCl (3*20 ml). The aqueous layer was basified with 3 N NaOH to pH>12 and extracted with EtOAc, (3*50 mL) to give crude product. The final product was purified by flash chromatography eluding with 5-10 % MeOH in dichloromethane. 1H NMR (400 MHz, CDCl3): delta7.66 (s, 1H), 7.32 (d, J=8.61 Hz, 1H), 7.01 (d, J=8.61 Hz, 1H), 4.26 (t, J=5.09 Hz, 2H), 2.67 (t J=5.48 Hz, 2H), 2.34 (s, 3H), 1.79 (m, 2H), 1.34 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | Step C. tert-Butyl 4-({1-[(octylamino)carbonyl]-4piperidinyl}oxy)phenethylcarbamate A solution of 4-hydroxy-N-octyl-1-piperidinecarboxamide (3.0 g, 11.7 mmol), and triphenylphosphine (3.28 g, 12.5 mmol) in anhydrous tetrahydrofuran was treated drop-wise at 0 C. with a solution of diisopropyl 1,2-diazenedicarboxylate (2.66 g, 12.5 mmol) in anhydrous tetrahydrofuran. A solution of tert-butyl 4-hydroxyphenethylcarbamate (2.85 g, 12 mmol) in anhydrous tetrahydrofuran was added drop-wise over a period of three hours while maintaining the reaction temperature at 0 C. during the addition. The stirred reaction mixture was allowed to warm to room temperature overnight. The solvent was evaporated in vacuo and the residue stirred with hexane-diethyl ether (~1:1). The precipitate (4.5 g) was filtered and discarded. The filtrate was evaporated in vacuo to an amber-colored, oily crude product (6.95 g). The crude product was purified by flash chromatography on silica gel Merck-60 (eluant: 3:1 going to 1:1 hexane-methanol) to give the title compound (2.5 g, 5.26 mmol). m.p. 79-81 C. MS ((+)APCI), m/z 476 [M+H]+ IR (KBr), v 3350, 1685, 1620, 1525, 1510, 1230, 1175 cm-1 1H NMR (DMSO-d6, 400 MHz) delta 7.06 (d, J=8.6 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.81 (t, J=5.5 Hz, 1H), 6.43 (t, J=5.5 Hz, 1H), 4.45 (tt, J=8.1, 4.2 Hz, 1H), 3.64 (ddd, J=14.1, 5.5, 4.2, 2H), 3.02-3.10 (m, 4H), 2.98 (q, J=6.8 Hz, 2H), 2.59 (t, J=7.9 Hz, 2H), 1.82-1.86 (m, 2H), 1.41- 1.47 (m, 2H), 1.38 (m, 2H), 1.35 (s, 9H), 1.24 (s, 1 OH), 0.85 (t, J=7.0 Hz, 3H) Analysis calc'd for C27H45N3O4: C 68.18, H 9.54, N 8.83: found: C 68.01, H 9.58, N 8.88 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; diethyl ether; hexane; | Step B. tert-Butyl 4-[(1-[(4-fluorobenzyl)amino]carbonyl}-4-piperidinyl)oxy]phenethylcarbamate A stirred solution of N-(4-fluorobenzyl)-4-hydroxy-1-piperidinecarboxamide (2.95 g, 11.7 mmol), and solid triphenylphosphine (3.28 g, 12.5 mmol) in anhydrous tetrahydrofuran (50 mL), was treated drop-wise at 0 C. under nitrogen with a solution of diisopropyl 1,2-diazenedicarboxylate (2.66 g, 12.5 mmol) in anhydrous tetrahydrofuran (10 mL). A solution of tert-butyl 4-hydroxyphenethylcarbamate (2.85 g, 12 mmol) in anhydrous tetrahydrofuran (25 mL) was added drop-wise over a period of three hours while maintaining the reaction temperature at 0 C. during the addition. The stirred reaction mixture was allowed to warm to room temperature overnight. Hexane and diethyl ether were added to the reaction mixture and the precipitate filtered. The precipitate was triturated with diethyl ether and re-filtered. The combined filtrates were evaporated in vacuo, and the resulting residue crystallized from a mixture of acetone-diethyl ether-hexane (1:1:1) to yield, after filtration and washing with cold diethyl ether, the title compound (1.25 g, 2.6 mmol). m.p. 126-128 C. MS ((+)APCI), m/z 472 [M+H]+ IR (KBr), v 3400, 1690, 1610, 1525, 1510, 1230, 1180 cm-1 1H NMR (DMSO-d6, 400 MHz) delta 7.26 (dd, J=8.8, 5.7 Hz, 2H), 7.11 (t, J=8.8 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.06 (1H), 6.86 (d, J=8.6 Hz, 2H), 6.83 (t, J=5.7 Hz, 1H), 4.47 (tt, J=7.9, 3.9 Hz, 1H), 4.20 (d, J=5.7 Hz, 2H), 3.68 (dt, J=14.3, 4.2 Hz, 1H), 3.12 (ddd, J=12.7, 9.2, 3.1 Hz, 2H), 3.06 (t, J=5.9 Hz, 2H), 2.59 (t, J=7.9 Hz, 2H), 1.84-1.89 (m, 2H), 1.46 (dddd, J=12.7, 8.8, 8.8, 3.7 Hz, 2H) 13C NMR (DMSO-d6, 100 MHz) delta 161.0 (d, JC-F=241.1 Hz, 1C), 157.2 (1C), 155.4 (1C), 155.3 (1C), 137 (1C), 131 (1C), 130 (2C), 128.8 (d, JC-F=8.4 Hz, 2C), 116 (2H), 114.7 (d, JC-F=21.4 Hz, 2C), 77 (1C), 72 (1C), 42.8 (2C), 41.7 (2C), 40.8 (2C), 34.6 (2C), 30.5 (2C), 28.2 (9C) Analysis calc'd for C26H34FN3O4: C 66.22 H 7.27 N 8.91 found: C 66.12 H 7.18 N 8.72 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | EXAMPLE 1B 2-Methoxy-5-nitro-1-((3R)-tetrahydrofuryloxy)benzene To a mixture of <strong>[636-93-1]2-Methoxy-5-nitrophenol</strong> (1.69 g, 10 mmol), triphenylphosphine (5.24 g, 20 mmol) and 3-(R)-hydroxytetrahydrofuran (1.80 g, 20 mmol) in anhydrous tetrahydrofuran (40 mL) was added drop-wise, with stirring, diisopropylazodicarboxylate (4.0 mL, 20 mmol) and the mixture was allowed to stir at room temperature for 16 h. The mixture was diluted with ether (150 mL) and washed with 2N NaOH (3*50 mL) and brine (50 mL), (MgSO4) and concentrated in vacuo. The crude residue was purified by flash column chromatography over silica gel (Biotage Flash 40M) eluding with 20% ethyl acetate in hexanes to give 1.05 g of product The following compounds were prepared in a similar manner as described above: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With triphenylphosphine; In tetrahydrofuran; | PRODUCTION EXAMPLE 29 Production of Compound (185) by Production Process G To a solution of 1.10 g of 3,5-dichloro-4-(3-hydroxypropoxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.56 g of <strong>[827-99-6]3-trifluoromethoxyphenol</strong> and 0.83 g of triphenylphosphine dissolved in 20 ml of tetrahydrofuran was added dropwise a solution of 0.64 g of diisopropylazodicarboxylate dissolved in 10 ml of tetrahydrofuran, while stirring at room temperature. After stirring at room temperature for 24 hours, the reaction mixture was concentrated to obtain a residue. The residue was subjected to silica gel chromatography, which afforded 1.03 g of 3,5-dichloro-4-(3-(4-trifluoromethoxyphenoxy) propoxy)-1-(3,3-dichloro-2-propenyloxy)benzene (64% yield), nD23.4 1.5343. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.2 g (83%) | With triphenylphosphine; In tetrahydrofuran; isopropyl alcohol; | a) A mixture of <strong>[41598-71-4]6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol</strong> (0.03544 mol), 3-hydroxy-4-methoxybenzaldehyde (0.0322 mol) and triphenylphosphine (0.0322 mol) in THF (100 ml) was stirred at 5 C. under N2 atmosphere. Bis(1-methylethyl) diazenedicarboxylate (0.0322 mol) was added dropwise and the resulting reaction mixture was stirred for 12 hours at RT. The solvent was evaporated. CH2 Cl2 was added to the residue. The mixture was washed with water, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2 Cl2 /CH3 OH from 100/0 to 98.5/1.5). The desired fractions were collected and the solvent was evaporated. The residue was dissolved in 2-propanol and converted into the hydrochloric acid salt (1:1) with HCl/2-propanol. The solvent was evaporated. The residue was stirred in DIPE, filtered off and dried, yielding 8.2 g (83%) of 3-[(5,6-dihydro-7H-pyrindin-7-yl)oxy]-4-methoxybenzaldehyde hydrochloride (intermediate 34). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | REFERENCE EXAMPLE 50 2-Fluoro-4-(thiazol-5-ylmethoxy)benzonitrile Diisopropylazodicarboxylate (4.0 g) was dissolved in a little anhydrous tetrahydrofuran (about 10 ml) and added dropwise to a stirred solution of triphenylphosphine (5.2 g) in anhydrous tetrahydrofuran (150 ml) at 0 C. under nitrogen. After stirring at 0 C. for 15 minutes, during which time a white precipitate formed, a mixture of 2-fluoro-4-hydroxybenzonitrile (S. M. Kelly, Helv.Chim.Acta. 1984, Volume 67, P.1572-1579) (2.0 g) and thiazole-5-methanol (2.3 g) in anhydrous tetrahydrofuran (20 ml) was added dropwise whilst maintaining the temperature at or below 5 C. The reaction mixture was stirred in the cooling bath for a further 2 hours then allowed to warm slowly to room temperature. After standing at room temperature overnight the reaction mixture was partitioned between ethyl acetate (200 ml) and saturated aqueous ammonium chloride solution (200 ml). The layers were separated and the organic phase washed with water (100 ml), dried over magnesium sulphate and evaporated. The residue was purified by flash chromatography on silica eluding with a mixture of ethyl acetate and cyclohexane (1:1, v/v). Fractions homogenous in the required product were combined and evaporated affording the title compound as a pale yellow solid (2.0 g). | |
With triphenylphosphine; In tetrahydrofuran; | REFERENCE EXAMPLE 50 2-Fluoro-4-(thiazol-5-ylmethoxy)benzonitrile Diisopropylazodicarboxylate (4.0 g) was dissolved in a little anhydrous tetrahydrofuran (about 10 ml) and added dropwise to a stirred solution of triphenylphosphine (5.2 g) in anhydrous tetrahydrofuran (150 ml) at 0 C. under nitrogen. After stirring at 0 C. for 15 minutes, during which time a white precipitate formed, a mixture of 2-fluoro-4-hydroxybenzonitrile (S. M. Kelly, Helv.Chim.Acta. 1984, Volume 67, P.1572-1579) (2.0 g) and thiazole-5-methanol (2.3 g) in anhydrous tetrahydrofuran (20 ml) was added dropwise whilst maintaining the temperature at or below 5 C. The reaction mixture was stirred in the cooling bath for a further 2 hours then allowed to warm slowly to room temperature. After standing at room temperature overnight the reaction mixture was partitioned between ethyl acetate (200 ml) and saturated aqueous ammonium chloride solution (200 ml). The layers were separated and the organic phase washed with water (100 ml), dried over magnesium sulphate and evaporated. The residue was purified by flash chromatography on silica eluding with a mixture of ethyl acetate and cyclohexane (1:1, v/v). Fractions homogenous in the required product were combined and evaporated affording the title compound as a pale yellow solid (2.0 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | Step 8.3 Under Mitsunobu conditions, diphenyl-(3,6,9,12,15-pentaoxa-hexadec-1-yl-oxy)-silanol is obtained analogously to Step 1.3., Variant a, from 2 g (7.83 mmol) of 3,6,9,12,15-pentaoxa-hexadecanol, 3.39 g (21.63 mmol) of diphenylsilanediol, 4.11 g (15.66 mmol) of triphenylphosphine and 3.2 ml (3.17 g; 15.7 mmol) of azodicarboxylic acid diisopropyl ester in 70 ml of tetrahydrofuran; NMR(CDCl3): 7.1-7.8 (m's, phenyl-H); 3.4-3.7 (m,OCH2 --CH2); 3.35 (s,3H,OCH3). Alternatively, the same compound can also be obtained in accordance with Step 3.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triphenylphosphine; In tetrahydrofuran; | Step e) (E)-N-tert-Butoxycarbonyloxy-(3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-enyl)-carbamic acid tert-butyl ester Diisopropylazodicarboxylate (1.98 ml, 10.07 mmol) in THF (15 ml) was added dropwise n to a cold (-20 C.) solution of (E)-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-en-1-ol (3.5 g, 8.39 mmol) in THF (30 ml), triphenylphosphine (2.64 g, 10.07 mmol) and tert-butyl N-(tert-butoxy-carbonyloxy) carbamate (2.35 g, 10.07 mmol). After the addition, the mixture was stirred for 1 hour, poured into water, and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on silica gel (hexane/EtOAc 7/1) gave a clear oil (5.1 g, 96% yield). Analysis for: C33 H39 F3 N2 O7 *0.5 H2 O Calc'd: C, 61.77; H, 6.24; N, 4.37 Found: C, 61.58; H, 6.46; N, 4.60 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triphenylphosphine; trifluoroacetic acid; In tetrahydrofuran; diethyl ether; dichloromethane; water; | Step b) (Z)-N-(3-{3-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-enyl)-hydroxylamine Diisopropylazodicarboxylate (0.68 ml, 3.45 mmol) in THF (10 ml) was added dropwise n to a cold (-20 C.) solution of (Z)-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-en-1-ol (1.2 g, 2.87 mmol), THF (20 ml), triphenylphosphine (0.9 g, 3.45 mmol) and tert-butyl N-(tert-butoxy-carbonyloxy) carbamate (0.8 g, 3.45 mmol). After the addition, the mixture was stirred for 1 hour, poured into water, and extracted with EtOAc. Evaporation gave a yellowish oil (1.7 g), which was dissolved in CH2 Cl2 (30 mL), and treated with trifluoroacetic acid (3.0 mL). After stirring at room temperature for 8 hours, the volatiles were removed in vacuo, and the residue taken in ethylether/water. It was basified to pH=9-10 with NaOH (2N), and the organic layer separated and washed with water and brine. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on silica gel (hexane/EtOAc 1/1, and MeOH/EtOAc 1/10), gave a white solid (3.0 g, 82% yield, m.p. 72-73 C.). Analysis for: C23 H23 F3 N2 O3 Calc'd: C, 63.88; H, 5.36; N, 6.48 Found: C, 63.74; H, 5.34; N, 6.26 |
82% | With triphenylphosphine; trifluoroacetic acid; In tetrahydrofuran; CH2 Cl2; diethyl ether; water; | Step b) (Z)-N-(3-{3-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-enyl)-hydroxylamine Diisopropylazodicarboxylate (0.68 ml, 3.45 mmol) in THF (10 ml) was added dropwise n to a cold (-20 C.) solution of (Z)-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-pent-2-en-1-ol (1.2 g, 2.87 mmol), THF (20 ml), triphenylphosphine (0.9 g, 3.45 mmol) and tert-butyl N-(tert-butoxy-carbonyloxy) carbamate (0.8 g, 3.45 mmol). After the addition, the mixture was stirred for 1 hour, poured into water, and extracted with EtOAc. Evaporation gave a yellowish oil (1.7 g), which was dissolved in CH2 Cl2 (30 mL), and treated with trifluoroacetic acid (3.0 mL). After stirring at room temperature for 8 hours, the volatiles were removed in vacuo, and the residue taken in ethylether/water. It was basified to pH=9-10 with NaOH (2N), and the organic layer separated and washed with water and brine. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography on silica gel (hexane/EtOAc 1/1, and MeOH/EtOAc 1/10), gave a white solid (3.0 g, 82% yield, m.p. 72-73 C.). Analysis for: C23 H23 F3 N2 O3 Calc'd: C, 63.88; H, 5.36; N, 6.48 Found: C, 63.74; H, 5.34; N, 6.26 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | Example 51 Preparation of 8-(3-chlorophenyl)-6-(6-methoxy-3-pyridylmethyl)pyrido[2,3-d]pyridazin-5-one Formula I, Where X Is Nitrogen, Y Is Carbon, Z Is Oxygen, R1 is 6-Methoxy-3-pyridylmethyl, R3 Is Chloro, And R2, R4, R5, R6 Are Hydrogen To a suspension of 8-(3-chlorophenyl)pyrido-[2,3-d]pyridazin-5-one (0.515 g, 2.0 moles), <strong>[58584-63-7]6-methoxy-3-hydroxymethyl pyridine</strong> (0,306g, 2.2 moles) and triphenylphosphine (0.792 g, 3.0 moles) in THF (50 mL) was added diisopropylazodicarboxylate (0.6mL, 3.0 moles). The reaction mixture was stirred for 18 hours at room temperature. The solvent was removed and the product was purified by chromatography (ethyl acetate/hexane 2:3) and crystallized from methanol to yield 0.588g of 8-(3-chlorophenyl)-6-(6-methoxy-3-pyridylmethyl)pyrido[2,3-d]-pyridazin-5-one, mp 145 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With sodium hydroxide; ammonium chloride; triphenylphosphine; In tetrahydrofuran; ethyl acetate; | PREPARATION 2 5-[(2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl)oxy]-1H-indole-1-carboxylic Acid 1,1-dimethylethyl Ester A solution of 1.75 g (7.51 mM) of <strong>[434958-85-7]5-hydroxy-1H-indole-1-carboxylic acid tert-butyl ester</strong> in 25 ml of THF, 2.73 g (13.5 mM) of diisopropylazodicarboxylate and 3.54 g (13.5 mM) of triphenylphosphine are added to a solution of 2.85 g (9.75 mM) of 2,3,4-tri-O-acetyl-5-thio-D-xylopyranose in 50 ml of THF. The reaction mixture is stirred at 45 C. for 3 hours and then concentrated under reduced pressure. The evaporation residue is dissolved in ethyl acetate and the organic phase is washed with a 1N solution of sodium hydroxide, and then with a concentrated aqueous solution of ammonium chloride. The organic phase is subsequently dried over magnesium sulfate and concentrated under reduced pressure. The evaporation residue is purified by C18-grafted silica chromatography, elution being carried out with an acetonitrile/water mixture (7/3; v/v). The desired product is obtained in the form of a pale yellow solid with a yield of 11%. Mp=58-62 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 16; 4-Phthalimido-5-hexenenitrile (33).; A solution of 32 (0.35 g, 3.1 mmol), triphenylphosphine (0.87 g, 3.3 mmol), and phthalimide (0.50 g, 3.3 mmol) in dry THF (15 mL) was stirred at 0 0C under N2 for 10 min. A solution of <strong>[2446-83-5]diisopropyl azodicarboxylate</strong> (DIAD, 0.66 g, 3.3 mmol) in THF (8 mL) was added dropwise over 20 min. The mixture was stirred at room temperature for 3 h. After the solvent was removed by rotary evaporation, the crude product was purified by chromatography on silica gel (ethyl acetate/hexanes, 1 :9) to give a mixture of 33 and diisopropyl hydrazodicarboxylate, a by-product formed from DIAD (1.19 g, -3:2 m/m, 97%). 1H NMR (400 MHz, CDCl3) £7.72-7.85 (m, 4H)5 6.14-6.23 (m, IH)5 5.34 (d, IH5 J= 17.2 Hz)5 5.26 (d, IH5 J= 10.4 Hz) 4.8 (tetra, IH5 J= 5.6 Hz), 2.27-2.48 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydride; In N,N-dimethyl-formamide; at 25℃; for 12h;Inert atmosphere; | General procedure: A mixture of aryl halide (1.0 mmol), DAAD (1.1 mmol), and CuI (9 mg, 0.05 mmol) in DMF (2 mL) was stirred for 30 min at 0 C. A suspension of NaH (0.050 g, 1.1 mmol) in DMF (1 mL) was slowly added to the reaction mixture over 20 min. The mixture was then evacuated and back-filled with N2 (3 times) and stirred for 12-20 h at the appropriate temperature. The crude reaction mixture was diluted with CH2Cl2 (5 mL) and a saturated NH4Cl solution (3 mL). The mixture was stirred for an additional 30 min and two layers were separated. The aqueous layer was extracted with CH2Cl2 (3 2 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane/EtOAc 3:1) to give the desired product. |
88% | With water; 5-methoxy-1,3,4-triphenyl-4,5-dihydro-1H-1,2-4-triazoline; In 1,2-dimethoxyethane; at 150℃; under 760.051 Torr;Inert atmosphere; Sealed tube; Microwave irradiation; | General procedure: A glass reaction vessel was sufficiently dried under a nitrogen atmosphere of 1 atm, stir bar, N- heterocyclic carbene precursor 1 (see FIG. 1) (0.89 mg, 0.30 mmol), water ( 14 mg, 0.78 mmol), 1,2- dimethoxyethane (0.80 mL), and the reaction substrate in which dibutyl fumarate (see FIG. 2) (57 mg, and 0.25 mmol) were added and sealed glass containers. This solution, via a microwave reactor, 100 or more, preferably is allowed to react for 2 hours or more at about 150 .By distillation under reduced pressure over 5.0 mmHg from the reaction mixture, to give a hydrogenated product (see FIG. 3) at 54 mg, 94% yield. This example is also in the same manner as in Example 1, the reaction was carried out using a substrate 26 (see FIG. 26) instead of dibutyl fumarate.The reaction mixture was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 3: 2, Rf = 0.6 )by purification by, hydrogenated product 27 (see FIG. 27) at 45 mg, 88% yield Obtained.Structural analysis of the product was also carried out in the same manner as in Example 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | General procedure: A mixture of aryl halide (1.0 mmol), DAAD (1.1 mmol), and CuI (9 mg, 0.05 mmol) in DMF (2 mL) was stirred for 30 min at 0 °C. A suspension of NaH (0.050 g, 1.1 mmol) in DMF (1 mL) was slowly added to the reaction mixture over 20 min. The mixture was then evacuated and back-filled with N2 (3 times) and stirred for 12?20 h at the appropriate temperature. The crude reaction mixture was diluted with CH2Cl2 (5 mL) and a saturated NH4Cl solution (3 mL). The mixture was stirred for an additional 30 min and two layers were separated. The aqueous layer was extracted with CH2Cl2 (3 2 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane/EtOAc 3:1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; | Example 167 5-Amino-N-[5-[5-(aminomethyl)-1,3-dioxan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2,6-difluorophenyl)thiazole-4-carboxamide 167 To a solution of (2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol (360 mg, 1.48 mmol, intermediate 68) in dry THF (12 mL) was added polymer supported triphenylphosphine (?3 mmol/g, 1.5 g, 4.44 mmol) and <strong>[88-96-0]phthalamide</strong> (326 mg, 2.22 mmol) followed by diisopropylazodicarboxylate (450 mg, 2.22 mmol). The reaction mixture was stirred at room temperature for 18 hr then heated at 35 C. for 4 hr. The reaction mixture was filtered and the filtrate diluted with DCM (50 mL) and washed with a saturated aqueous NaHCO3 (25 mL). The organic layer was washed with water (25 mL) and brine (25 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-((2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methyl)isoindoline-1,3-dione as a colourless solid (226 mg) contaminated with diisopropyl azodicarboxylate byproduct. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With triphenylphosphine; In tetrahydrofuran; | Step 1: methyl 5-((4-hydroxybut-2-yn-1-yl)oxy)picolinate In a 500-mL flask, but-2-yne-1,4-diol (5.62 g, 65.3 mmol), <strong>[30766-12-2]methyl 5-hydroxypicolinate</strong> (5.00 g, 32.7 mmol) and triphenylphosphine (12.85 g, 49.0 mmol) were suspended in THF (100 mL). The suspension was cooled to 0 C., and (E)-diisopropyl diazene-1,2-dicarboxylate (9.52 mL, 49.0 mmol) was added over 1 minute. The reaction was stirred at 0 C. for 2 h, then at RT for 2 h. The reaction was filtered through Celite, rinsing with DCM (500 mL). The filtrate was concentrated and the residue was chromatographed on silica gel (600 mL), eluent 2% to 3% MeOH-DCM to afford the title compound (3.43 g, 48%). MS: m/z=222 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triphenylphosphine; In dichloromethane; at 0 - 20℃; for 0.333333h;Inert atmosphere; Schlenk technique; | General procedure: Under N2 atmosphere and at 0 C, to a stirred solution of MBHalcohols 1 (0.3 mmol) and PPh3 (0.6 mmol) in EtOAc orCH2Cl2 (2 mL) in a Schlenk tube (25 mL) was slowly addedazodicarboxylates 2 (0.6 mmol) over 5 minutes by the means ofa microsyringe. The resulting reaction mixture was allowed towarm up to room temperature and stirred until the MBH alcohols1 were completely consumed, as monitored by TLC. Thesolvent was removed under reduced pressure and the residuewas purified by column chromatography on silica gel (gradienteluant: petroleum ether/ethyl acetate 9:1-3:1) to afford thehydrazines 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In methanol; at 20℃; for 12h;Green chemistry; | General procedure: To a mixture of sulfinic acids 1 (0.6 mmol) and azodicarboxylates 2 (0.5 mmol) in a 25 mL round-bottomed flack at room temperature, was added the CH3OH (2 mL). The reaction vessel was allowed to stir at room temperature for 12h. After the reaction, the solvent was then removed under vacuum. The residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent to give the desired product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | General procedure: A mixture of aryl halide (1.0 mmol), DAAD (1.1 mmol), and CuI (9 mg, 0.05 mmol) in DMF (2 mL) was stirred for 30 min at 0 C. A suspension of NaH (0.050 g, 1.1 mmol) in DMF (1 mL) was slowly added to the reaction mixture over 20 min. The mixture was then evacuated and back-filled with N2 (3 times) and stirred for 12-20 h at the appropriate temperature. The crude reaction mixture was diluted with CH2Cl2 (5 mL) and a saturated NH4Cl solution (3 mL). The mixture was stirred for an additional 30 min and two layers were separated. The aqueous layer was extracted with CH2Cl2 (3 2 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane/EtOAc 3:1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To the stirred solution of <strong>[722-92-9]2-(4-aminophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol</strong> (1.0 g, 3.86 mmol) in dry tetrahydrofuran (THF) under inert atmosphere, triphenylphosphine (3.04 g, 11.58 mmol) was added and stirred for 20 minutes. (E)-Diisopropyl diazene-1,2- dicarboxylate (0.936 g, 4.63 mmol) and methanol (0.23 mL, 5.79 mmol) were added to the reaction mixture at 0-5 °C. The reaction mixture was refluxed for 4-5 hours. Aftercompletion of the reaction, the reaction mixture was diluted with methylene chloride and purified using column chromatography (silica gel, hexane and ethyl acetate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1,3,4-triphenyl-1,2,4-triazolium hexafluorophosphate; potassium tert-butylate; In chloroform; at 20℃; for 4h;Inert atmosphere; | General procedure: To a flame dried test tube equipped with a magnetic stirring bar, was added NHC precatalyst (10 mol %). The test tube was evacuated and flushed with argon, and then, KOtBu (0.2 equiv,0.042 mmol, 9.2 mg) and CHCl3 (1 ml) were added and stirred for 1 h. Then, the solution of naphthol derivatives (0.208 mmol, 30 mg) and dialkyl azodicarboxylates (2 equiv) inCHCl3 was added to the test tube. The reaction mixture was stirred at room temperature for 4 h. After completion of the reaction, sat. NH4Cl solution was added and the aqueous layer was then extracted with ethyl acetate and dried over sodium sulphate, and purified using column chromatography (ethyl acetate/petroleum ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With cerium(IV) trifluoromethanesulfonate; 9,10-diphenylanthracene; tetrabutyl-ammonium chloride; titanium tetrachloride; In chlorobenzene; acetonitrile; at 0 - 50℃; for 24h;Inert atmosphere; Irradiation; Glovebox; | General procedure: A 8-mL vial was charged with cyclobutanone (15 muL, 0.2 mmol, 1.0 equiv.),diisopropyl azodicarboxylate (DIAD) (48 muL, 0.24 mmol, 1.2 equiv.), DPA (3.3 mg, 10mumol, 0.05 equiv.), Ce(OTf)4 (2.9 mg, 4 mumol, 0.02 equiv.), n-Bu4NCl (5.5 mg, 20 mumol,0.1 equiv.) in glovebox, then the vial was sealed with a polytetrafluoroethylene-linedcap before CH3CN (1.5 mL), PhCl (0.5 mL) was added. TiCl4 (0.1 mL, 0.2 M in CH3CN,0.1 equiv.) and TMSCN (76 muL, 0.6 mmol, 3 equiv.) was added at 0 C. The reactionmixture was degassed by Argon sparging for 2 min at 0 C, then irradiated with a 100W blue LED lamp (at approximately 4 cm away from the light source, light intensity0.16 Wcm-2, the reaction temperature was measured to be 50 C). After the ketonewas consumed, the reaction mixture was cooled to room temperature and quenchedwith saturated aq. NaHCO3 (1 mL). The solution was extracted by ethyl acetate (3×3mL), and dried over anhydrous Na2SO4. After filtration, the filtrate was concentratedin vacuo. Purification by flash chromatography on silica gel (20% acetone in hexanes)provided the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77%Chromat.; 74% | General procedure: A 8-mL vial was charged with 2-phenylcyclohexanone (35 mg, 0.2 mmol, 1.0equiv.), DIAD (48 muL, 0.24 mmol, 1.2 equiv.), DPA (3.3 mg, 10 mumol, 0.05 equiv.),Ce(OTf)4 (2.9 mg, 4 mumol, 0.02 equiv.), n-Bu4NCl (5.5 mg, 20 mumol, 0.1 equiv.) inglovebox, then the vial was sealed with a poly-tetrafluoroethylene-lined cap before CH3CN (1 mL), PhCF3 (1 mL) was added. TiCl4 (0.1 mL, 0.2 M in CH3CN, 0.1 equiv.)and TMSCN (76 muL, 0.6 mmol, 3 equiv.) was added at 0 C. The reaction mixture wasdegassed by Argon sparging for 2 min at 0 C, then irradiated with a 100 W blue LEDlamp (at approximately 4 cm away from the light source, light intensity 0.16 Wcm-2,the reaction temperature was measured to be 50 C). After the ketone was consumed,the reaction mixture was cooled to room temperature before anhydrous methanol (4mL) and Et3N (42 muL, 0.3 mmol, 1.5 equiv.) was added. The solution was stirred foranother 2h before concentrated in vacuo. Purification by flash chromatography onsilica gel (20% acetone in hexanes) provided the desired product. |
Tags: 2446-83-5 synthesis path| 2446-83-5 SDS| 2446-83-5 COA| 2446-83-5 purity| 2446-83-5 application| 2446-83-5 NMR| 2446-83-5 COA| 2446-83-5 structure
[ 870-50-8 ]
Di-tert-butyl diazene-1,2-dicarboxylate
Similarity: 0.97
[ 870-46-2 ]
tert-Butyl hydrazinecarboxylate
Similarity: 0.62
[ 870-50-8 ]
Di-tert-butyl diazene-1,2-dicarboxylate
Similarity: 0.97
[ 2449-05-0 ]
Dibenzyl diazene-1,2-dicarboxylate
Similarity: 0.60
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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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