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Synonyms: EMTC; NSC 400231
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CAS No. : | 7210-76-6 |
Formula : | C7H10N2O2S |
M.W : | 186.23 |
SMILES Code : | C(OC(C1=C(N=C(S1)N)C)=O)C |
Synonyms : |
EMTC; NSC 400231
|
MDL No. : | MFCD00123414 |
InChI Key : | WZHUPCREDVWLKC-UHFFFAOYSA-N |
Pubchem ID : | 343747 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
74% | at 140 - 150℃; for 1h; | Ethyl 2-amino-4-methylthiazole-5-carboxylate (0.01 mol) was taken in a round bottom flask and acetic anhydride (0.02 mol) was added. The reaction mixture was refluxed at 140-150 C for 1 h and then poured into cold water under constant stirring to get solid product. The mixture was heated to boiling to decompose excess of acetic anhydride and cooled. The solid obtained was filtered, washed with water and dried. The ethyl 2-(acetyl amino)-4-methyl-1,3-thiazole-5-carboxylate was collected and recrystallized from ethanol to get pure white crystals. Yield: 74%; m.p. 158 C; Anal. obs. C, 47.08%; H, 5.48%; N, 12.44%. Calcd. for C9H12N2O3S: C, 47.35%; H, 5.30%; N, 12.27%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With polyethylene glycol (PEG-400); In water; for 0.133333h;Microwave irradiation; Green chemistry; | To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With pyridine; for 3h;Reflux; | General procedure: A mixture of the start 1 (0.93 g, 5 mmol) and benzenesulfonylchloride or tosyl chloride (5 mmol) in pyridine (10 mL) was heatedunder reflux for 3 h. Working up of the reaction mixture was carriedout as described under 4. Physicochemical and analytical dataare recorded in Table 3. IR (cm-1): 3380-3125 (NH), 1690-1680(C=O), 1110-1017 (SO2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine hydrate; In ethanol; at 20℃; for 3h; | General procedure: A mixture of substituted ethyl benzoate 2 (10 mmol) and hydrazinehydrate (20 mmol) in ethanol was stirred at room temperaturefor 3 h and then filtered. The crude product recrystallizedfrom absolute alcohol to give 3a-l, which were used directly forthe next step. Under this same condition, the intermediate compounds8a-d were also prepared. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 75℃; for 4h;Sealed tube; | Acetoferulic acid E3 (2 mmol) was suspended in toluene (2 mL),thionyl chloride (0.5 mL), 1 drop of N, N-dimethylformamide wereadded dropwise in turn. The mixture reacted at 60 C for 5 h. Thenremove the solvent and remaining thionyl chloride to obtain crudeacetylferulyl chloride F3. Potassium thiocyanate (2.5 mmol) wasdissolved in 5 mL acetonitrile, and 5 mL of the acetonitrile solutionof the F3 was added dropwise to it. After the addition wascompleted, the reaction was carried out at room temperature for5 h, and then filtered to obtain acetyl ferulyl isocyanate (G3)acetonitrile solution. Ethyl 2-amino-4-methyl- thiazole-5-carboxylate (1.5 mmol, A1) was added to this solution in twobatches, heated to 75 C and reacted for 4 h, cooled to room temperature,sealed and refrigerated, filtered, washed with ethanol,and dried to obtain target compounds S3. m.p. 237-239 C, yield44.2%; 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (t, J 6.8 Hz, 3H, CH3),2.56 (s, 3H, thiazole-CH3), 4.24 (q, J 6.8 Hz, 2H, OCH2), 6.99 (d,J 15.8 Hz, 1H, CH), 7.46-7.49 (m, 3H, C6H5), 7.60-7.68 (m, 2H,C6H5), 7.79 (d, J 15.8 Hz, 1H, CH), 12.24 (s, 1H, NH), 14.17 (s, 1H,NH); Anal. Calcd. for C17H17N3O3S2: C, 54.38; H, 4.56; N,11.19; foundC, 36.13; H, 3.38; N, 12.64. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium hydroxide; In ethanol; at 20℃; for 26h; | To a solution of ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate 5 (3.00g, 16.1mmol) in ethanol (100mL) was added 1M sodium hydroxide solution (50.0mL) at room temperature, and the mixture was stirred for 26h. After the volatiles of the mixture were removed in vacuo, water and acetic acid were added to the residue to adjust the pH to 5.0. The resulting precipitate was collected by filtration, washed with water, and dried in vacuo to yield 6 (2.48g, 97%) as a colorless powder. 1H NMR (200MHz, DMSO-d6) δ 2.35 (s, 3H), 7.57 (s, 2H); MS (ESI): m/z 159 [M+H]+, 157 [M-H]-. |
94% | A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135.0 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was neutralized with 5% hydrochloric acid solution to pH 5~6. The precipitate obtained was collected by filtration and dried to afford the crude 2-amino-4-methylthiazole-5- carboxylic acid (5.20 g, 94%): 1H NMR (300 MHz, DMSO-J6) δ 7.63 (s, 2H), 2.30 (s, 3H); MS (ES+) m/z 159.1 (M + 1). | |
94% | PREPARATION 1; Preparation of 2-amino-7V-benzyl-4-methylthiazole-5-carboxamide; A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was <n="93"/>neutralized with 5% hydrochloric acid solution to pH 5-6. The precipitate obtained was collected by filtration and dried to afford the crude 2-amino-4-methylthiazole-5- carboxylic acid (5.20 g, 94%): 1H NMR (300 MHz, DMSO-J6) δ 7.63 (s, 2H), 2.30 (s, 3H); MS (ES+) nv'z 159.1 (M + 1).; PREPARATION 13; Preparation of 2-amino-4-methyl-7V-(pyridin-3-ylmethyl)thiazole-5-carboxamide; A. A solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.00 mmol) and sodium hydroxide (5.40 g, 135.00 mmol) in the mixture of tetrahydrofuran (60 mL) and water (30 mL) was heated at reflux for 18 hours. The tetrahydrofuran was removed in vacuo, and the aqueous solution was neutralized with 5% HCl solution to pH 5-6. The precipitated solid was collected by filtration, washed with water and dried to afford 2-amino-4-methylthiazole-5-carboxylic acid as a white solid in 94% yield (5.20 g): 1H NMR (300 MHz, DMSO-4) δ 7.63 (s, 2H), 2.30 (s, 3H); MS (ES+) m'z 159.1 (M + 1 ). |
81% | With sodium hydroxide; In ethanol; at 20℃; | The thiazole ethyl ester (1.0 g, 5.81 mmol) was treated with 0.5 M ethanolic sodium hydroxide solution (60 mL), overnight at room temperature. The reaction mixture was then cooled in an ice bath, and neutralized with acetic acid. The precipitated acid 2 was filtered, washed with diethyl ether, and dried overnight at 60 C.Yield: 81%; off-white crystals, mp 225-227 C (lit. [31] 223 C). 1HNMR (400 MHz, DMSO-d6): 2.35 (s, 3H, CH3), 7.61 (s, 2H, NH2),12.26(br s, 1H, COOH) ppm. HRMS (ESI): m/z [M H] calcd forC5H7N2O2S 159.1698; found 159.1663. |
79% | With sodium hydroxide; In methanol;Reflux; | Ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate(2) (0.075 M) and sodium hydroxide (0.3 M) in methanol were taken in 50 mL round bottom flask. The solution was refluxed with stirring until the reaction was complete. The clear solution was cooled and neutralized with glacial acetic acid and stirred for 30 min. Precipitate obtained was filtered, washed with water, dried and recrystallized with ethanol. The progress of the reaction and purity of the compound were checked by TLC, using benzene : acetone (8 : 2) as mobile phase. Yield: 79%; m.p.: 160-162C; IR (KBr v max) : 3370, 3055, 1741, 1645, 1492, 1388, 913, 728 cm-1; 1H-NMR (300 MHz, DMSO-d6, δ, ppm): 2.71 (s, 3H, CH3), 5.98 (bs, 2H, D2O exchangeable NH2), 10.71 (bs, 1H, COOH); 13C-NMR (75 MHz, CDCl3, δ, ppm): 13.91, (CH3), 133.59, 147.27, 169.54 (-C=O), 173.49 (-C-NH2, thiazole); ESI-MS: m/z 159.13 (M+H), 181.17 (M+Na); Analysis: calcd. for C5H6N2O2S: C, 37.97; H, 3.82; N, 17.71%; found: 37.93; H, 3.84; N, 17.76%. |
75 - 94% | A. To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (2.19 g, 11.8 mmol) in a 1 :1 mixture of tetrahydrofuran (20 mL) and water (10 mL) was added sodium hydroxide (1.80 g, 45.0 mmol). The reaction mixture was refluxed for 18 hours and allowed to cool down to ambient temperature. The organic solvent was removed in vacuo. The aqueous solution was acidified with 10% aqueous hydrochloric acid solution. The colorless solid was collected and dried to afford 2-amino-4-methylthiazole-5- carboxylic acid (1.40 g, 75%): 1H NMR (300 MHz, DMSO-J6) δ 11.95 (s, IH), 7.26 (s, 2H), 2.01 (s, 3H); MS (ES+) m/z 159.3 (M + 1).A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.50 mmol) and NaOH (5.40 g, 135.0 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was neutralized with 5% hydrochloric acid solution to pH 5~6. The precipitate obtained was collected by filtration and dried to afford the crude 2-amino-4-methylthiazole-5- carboxylic acid (5.20 g, 94%): 1H NMR (300 MHz, DMSO-J6) δ 7.63 (s, 2H), 2.30 (s, 3H); MS (ES+) m/z 159.1 (M + 1). | |
An aqueous solution of 1M-sodium hydroxide (50 ml) was added to an ethanol solution (100 ml) of ethyl 2-amino-4-methylthiazole-5-carboxylate (3.0 g) and the mixture was stirred at room temperature for 26 hours. After distilling off the solvent, acetic acid was added thereto under ice cooling (pH=5). Water was added thereto, the resultant mixture was stirred, and the crystal was collected by filtration. The crystal was washed with water, thereby obtaining 2-amino-4-methyl-thiazole-5-carboxylic acid (2.5 g) as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; water; In tetrahydrofuran;Heating / reflux; | A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135.00 mmol) in tetrahydrofuran (60 ml_) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed by evaporation, and the residue was neutralized with 5% hydrochloric acid solution to pH 5-6. The precipitate obtained was collected by filtration and dried to afford 2-amino-4-methylthiazole-5- carboxylic acid (5.20 g, 94%); 1H NMR (DMSO-d6, 300 MHz) δ 7.63 (s, 2H), 2.30 (s, 3H). MS (ES+) m/z 159.1 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine; In tetrahydrofuran; at 20℃; for 48h; | Synthesis of Ethyl 2-(lsonicotinamido)-4-methylthiazole~5~carboxylateTo a mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (5.70 g, 30.60 <n="93"/>mmol) and triethylamine (10.0 ml_, 71.80 mmol) in tetrahydrofuran (100 ml_) was added isonicotinoyl chloride hydrochloride (6.00 g, 32.00 mmol). The reaction mixture was stirred at ambient temperature for 2 days. The solvent was removed by evaporation and the resulting white solid was washed sequentially with water, 10% sodium bicarbonate solution, and water, then dried to afford the title compound in 90% yield (8.10 g); 1H NMR (DMSO-d6, 300 MHz) δ 8.77 (d, J = 6.0 Hz, 2H), 8.77 (d, J = 6.0 Hz, 2H), 4.23 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H). 1.27 (t, J = 7.2 Hz, 3H); MS (ES+) m/z 292.0 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With pyridine; In dichloromethane; | A. Ethyl-2-[(methylsulfonyl)amino]4-methyl-thiazole-5-carboxylate A stirred solution of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (558 mg, 3 mmol) in dichloromethane (15 mL) and pyridine (5 mL) was treated with methanesulfonyl chloride (687 mg, 6 mmol) at rt overnight. The solution was diluted with dichloromethane (50 mL) and washed with 2N aq. HCl solution (15 mL, 3*), dried (MgSO4), filtered and concentrated. The crude residue was diluted with ether (25 mL) and the solid was filtered, washed with 1:1 ether:hexane mixture (10 mL, 3*), and dried in vacuo to obtain the title compound (687 mg, 87%) as an off-white solid. |
87% | With pyridine; In dichloromethane; at 20℃; | [0392] A stirred solution of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (558 mg, 3 mmol) in dichloromethane (15 mL) and pyridine (5 mL) was treated with methanesulfonyl chloride (687 mg, 6 mmol) at rt overnight. The solution was diluted with dichloromethane (50 mL) and washed with 2N aq. HCl solution (15 mL, 3×), dried (MgSO4), filtered and concentrated. The crude residue was diluted with ether (25 mL) and the solid was filtered, washed with 1:1 ether:hexane mixture (10 mL, 3×), and dried in vacuo to obtain the title compound (687 mg, 87%) as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 5℃; for 4h; | [0318] A 3 M aq. NaHCO3 solution (10 mL, 30 mmol) was added to a stirred solution of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (372 mg, 2 mmol) in THF (20 mL) at 0-5)C. Benzyl chloroformate (500 μL) was added. After 2 h, additional benzyl chloroformate (500 μL) and the biphasic solution was stirred for an additional 2 h at 0-5C. The mixture was diluted with dichloromethane (50 mL) and water (30 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The residue was chromatographed on a silica gel column. Elution with 10% EtOAc in hexanes followed by 20% and 30% EtOAc in hexanes afforded the title compound (310 mg, 48%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; benzyl chloroformate; In dichloromethane; at 20℃; for 1h; | [0285] Benzyloxychloroformate (CbzCl, 3.92 mL, 27.4 mmol) was added to a r.t. solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (7, 5.11 g, 27.4 mmol), pyridine (4.44 mL, 54.9 mmol), and CH2Cl2 (200 mL). After 1 hour, the reaction mixture was washed with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), and brine (100 mL). The organic layer was dried (MgSO4), filtered, and concentrated. The resulting white solid was used without further purification. [0286] The above aminothiazole (300 mg, 0.94 mmol), sodium hydride (75 mg, 1.90 mmol), iodomethane (0.12 mL, 1.90 mmol), and DMF (5 mL) was maintained at r.t. for 1 hour. The reaction mixture was diluted with EtOAc (30 mL) and washed with saturated aqueous NH4Cl (20 mL), saturated aqueous NaHCO3 (20 mL), and brine (2×20 mL). The organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was purified by flash column chromatography (5:1 hexanes:EtOAc) to yield 250 mg (80%) of product. [0287] The above methylated aminothiazole (250 mg, 0.75 mmol), 10% Pd on carbon (100 mg), and EtOAc (15 mL) was hydrogenated (1 atm) for 3 h at r.t. The reaction mixture was then filtered through Celite and concentrated to provide 150 mg (100%) of 21. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 23℃; for 19h; | [0263] A mixture of Boc-Valine (6, 7.5 g, 34.5 mmol), ethyl 2-amino-4-methylthiazole-5-carboxylate (7, 6.5 g, 34.9 mmol), EDCI (8.0 g, 41.7 mmol), DIEA (22 mL, 126 mmol), DMAP (600 mg, 4.9 mmol), and CH2Cl2 (70 mL) were maintained at 23 C. for 19 hours. The reaction mixture was diluted with EtOAc (500 mL) and washed with saturated aqueous NH4Cl (2×100 mL), 0.5 N NaOH (100 mL), and brine (100 mL). The organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was purified by flash column chromatography (3:1 hexanes:EtOAc) to yield 11.0 g (83%) of 8. LRMS (MH) m/z 386.1. [0264] Amide 8 (11.0 g, 28.5 mmol) and TFA:H2O (97.5:2.5, 60 mL) was maintained at 23 C. for 1 h. The reaction mixture was concentrated to provide a colorless oil, which was used without further purification. [0265] A solution of a portion of the above crude amine (3.99 g, 10.0 mmol), anthranilic acid (2, 1.37 g, 10.0 mmol), HATU (4.18 g, 11.0 mmol), TEA (4.1 mL, 30.0 mmol), and DMF (40 mL) was maintained at 23 C. for 6 hours. The reaction mixture was diluted with EtOAc (200 mL) and washed with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), and brine (2×100 mL). The organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was purified by flash column chromatography (3:1 hexanes:EtOAc; 2:1 hexanes:EtOAc; 1:1 hexanes:EtOAc) to yield 3.13 g (77%) of 9. LRMS (MH) m/z 405.1. [0266] A solution of amide 9 (3.13 g, 7.75 mmol), carbonyldiimidazole (3.75 g, 23.2 mmol), and DMF (50 mL) was maintained at 70 C. for 1 hour. The reaction mixture was cooled to r.t., diluted with EtOAc (200 mL) and washed with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), and brine (2×100 mL). The organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was purified by flash column chromatography (3:1 hexanes:EtOAc; 2:1 hexanes:EtOAc; 1:1 hexanes:EtOAc) to yield 2.67 g (80%) of 6. LRMS (MH) m/z 431.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With trimethylsilyl bromide; In ethyl acetate; acetonitrile; at 0 - 20℃; | [2-BROMO-4-METHYL-THIAZOLE-5-CARBOXVLIC] acid ethyl ester To a solution of 3-methyl-1-nitrosooxy-butane (19.8 mL, 2.1 eq) in acetonitrile (700 mL) was added at [0XB0;C] trimethylsillyl bromide (19.6 mL, 2.1 eq) and the mixture was stirred at [0XB0;C] for 20 min. A solution of 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (14.0 g, 1.0 eq) in acetonitrile/EtOAc : 75/25 (700 mL) was added slowly at [0XB0;C.] After stirring overnight at rt, the reaction mixture was evaporated and purified by flash chromatography to give the title compound (13.2 g, 0. [051MOL)] as an orange solid in a 70% yield ; GC/MS: [M C7H8BRNO2S] 250;'H NMR [(CDC13,] 300 MHz) 5 4.32 (q, 2H), 2.69 (s, 3H), 1.34 (t, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In DMF (N,N-dimethyl-formamide); at 2 - 25℃; for 48h; | A mixture of 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (1.0 g, 5.4 mmol) inN,N-dimethylformamide at [25 oC] was treated with triethylamine (1.89 mL, 13.5 mmol) and triphenylmethylchloride (1.66 g, 5.94 mmol). The reaction was stirred at [2 oC] for 2 days. At this time, the reaction was concentrated in vauco. The residue was dissolved in dichloromethane (100 mL) and was washed with a IN aqueous hydrochloric acid solution (1 x 20 mL), a saturated aqueous sodium bicarbonate solution [(1] x 20 mL), and a saturated aqueous sodium chloride solution [(1] x 20 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 4-methyl-2- (trityl-amino)-thiazole-5-carboxylic acid ethyl ester (2.3 g, quant.). The product was used without further purification: LR-MS for [C26H24N202S] [(M-H) +] at [RN/Z = 427.] |
With triethylamine; In dichloromethane; N,N-dimethyl-formamide; | Step 1: Preparation of 4-methyl-2-(trityl-amino)-thiazole-5-carboxylic acid ethyl ester. A mixture of 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (1.0 g, 5.4 mmol) in N,N-dimethylformamide at 25 C. was treated with triethylamine (1.89 mL, 13.5 mmol) and triphenylmethylchloride (1.66 g, 5.94 mmol). The reaction was stirred at 2 C. for 2 days. At this time, the reaction was concentrated in vauco. The residue was dissolved in dichloromethane (100 mL) and was washed with a 1N aqueous hydrochloric acid solution (1*20 mL), a saturated aqueous sodium bicarbonate solution (1 x 20 mL), and a saturated aqueous sodium chloride solution (1*20 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 4-methyl-2-(trityl-amino)-thiazole-5-carboxylic acid ethyl ester (2.3 g, quant.). The product was used without further purification: LR-MS for C26H24N2O2S (M-H)+ at m/z=427. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | Ethyl 2-amino-4-methyl thiazole-5-carboxylate (50 mg, Avocado Research Chemicals LTD), 140 mg of N,N-Di-Boc-lysine, 95 μl of DIEA, and 153 mg of HBTU were dissolved in 1.5 ml of DMF. After stirring at RT for 48 hours, the reaction was quenched by addition of 0.5 ml water and diluted with 40 ml of EtOAc. The organic layer was washed with 1N HCl, brine and worked-up as described in General Procedure. Pure title compound (1B) was obtained by purification on a fresh silica gel column eluted with 30% EtOAc in hexane (30 mg, yield 22%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Ethyl 2-amino-4-methyl thiazole-5-carboxylate (500 mg), 1.5 grams of N-Cbz-N-Boc-lysine, 0.99 ml of DIEA, and 2.0 grams of HBTU were dissolved in 15 ml DMF. After stirring at RT for 48 hours, the reaction was quenched by addition of 0.5 ml of water and diluted with 40 ml of EtOAc. The organic layer was washed with 1N HCl, brine and worked-up as described in General Procedure. Pure title compound (1C) was obtained by purification on a fresh silica gel column eluted with 30% EtOAc in Hexane (1.3 grams, 88%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With hydrogenchloride;copper(I) chloride; In water; acetonitrile; | B. Ethyl 2-chloro-4-methyl-5-thiazolecarboxylate To a mixture of t-butyl nitrite (8.30 g, 80 mmol), cuprous chloride (6.38 g, 65 mmol) in 400 mL of acetonitrile was added Ethyl 2-Amino-4-methyl-5-thiazole-carboxylate (10 g, 54 mmol) in one portion. The thiazole dissolved after 25 minutes, and the reaction was allowed to stir at room temperature for 2 hours. The temperature was then increased to 66 C. for one hour. The solution was gradually allowed to cool to room temperature and filtered. The filtrate was poured into 400 mL of 6N HCl (the solution began fizzing). The solution was strirred for 20 minutes at which time TLC analysis showed that all of the starting material had been consumed and one product formed. The aqueous mixture was diluted with 700 mL of H2O and then extracted with ethyl acetate (4*400 mL). The ethyl acetate fractions were dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 10.45 g (94% yield) of a reddish oil which crystallized to a reddish-orange solid: 1H NMR (CDCl3) δ4.35 (q, 2H), 2.7 (s, 3H), 1.35 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; In tetrahydrofuran; dichloromethane; | A. Ethyl-2-tert-butoxycarbonyloxyamino-4-methyl-thiazole-5-carboxylate A suspension of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (18.6 g, 100 mmol), di-t-butyldicarbonate (26.2 g, 120 mmol) and 4-dimethylaminopyridine (800 mg, 6.55 mmol) in dry tetrahydrofuran (300 mL) was stirred under nitrogen for 18 h. The solvent was evaporated in vacuo. The residue was suspended in dichloromethane (1 L) and filtered through a pad of celite. The filtrate was washed with 1 N aqueous HCl solution (300 mL, 2*), water and brine, dried (MgSO4), and concentrated in vacuo. The residue was triturated with hexanes. The solid was filtered and dried in vacuo to obtain the title compound (20 g, 72%) as a tan solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With sodium hydrogencarbonate; In tetrahydrofuran; ethyl acetate; | A. Ethyl-2-benzyloxycarbonyloxyamino-4-methyl-thiazole-5-carboxylate A 3 M aq. NaHCO3 solution (10 mL, 30 mmol) was added to a stirred solution of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (372 mg, 2 mmol) in THF (20 mL) at 0-5 C. Benzyl chloroformate (500 μL) was added. After 2 h, additional benzyl chloroformate (500 μL) and the biphasic solution was stirred for an additional 2 h at 0-5 C. The mixture was diluted with dichloromethane (50 mL) and water (30 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The residue was chromatographed on a silica gel column. Elution with 10% EtOAc in hexanes followed by 20% and 30% EtOAc in hexanes afforded the title compound (310 mg, 48%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With hydrogenchloride;copper(I) chloride; In acetonitrile; | B. Ethyl 2-chloro-4-methyl-5-thiazolecarboxylate To a mixture of t-butyl nitrite (8.30 g, 80 mmol), cuprous chloride (6.38 g, 65 mmol) in 400 mL of acetonitrile was added Ethyl 2-Amino-4-methyl-5-thiazole-carboxylate (10 g, 54 mmol) in one portion. The thiazole dissolved after 25 minutes, and the reaction was allowed to stir at room temperature for 2 hours. The temperature was then increased to 66 C. for one hour. The solution was gradually allowed to cool to room temperature and filtered. The filtrate was poured into 400 mL of 6N HCl (the solution began fizzing). The solution was strirred for 20 minutes at which time TLC analysis showed that all of the starting material had been consumed and one product formed. The aqueous mixture was diluted with 700 mL of H2 O and then extracted with ethyl acetate (4*400 mL). The ethyl acetate fractions were dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 10.45 g (94% yield) of a reddish oil which crystallized to a reddish-orange solid: 1 H NMR (CDCl3) 67 4.35 (q, 2H), 2.7 (s, 3H), 1.35 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.3 g (78%) | With bromine; thiourea; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; diethyl ether; ethanol; water; | EXAMPLE 22A ethyl 2-amino-4-methylthiazole-5-carboxylate A 50 mL round-bottom flask was charged with ethyl acetoacetate (6.4 mL, 50 mmol) and water (25 mL). Bromine (2.8 mL, 51 mmol) was added over 30 minutes and an orange solution formed. The reaction was added to diethyl ether (100 mL). The organic layer was dried (MgSO4) and solvent removed under vacuum. The remaining orange gel was added to a refluxing solution of thiourea (8.95 g, 117.5 mL) in ethanol (25 mL). The reaction was refluxed for approximately 2 hours, cooled slightly, and poured into 50 mL of ice water. The pH was adjusted to ca.7-9 with NH40H. A thick white precipitate formed. The mixture was filtered to collect the solid. The product was recrystallized from 95% EtOH to provide 7.3 g (78%) of the title compound as a white, fluffy crystalline solid. 1H NMR (300 MHz, CDCl3) δ 4.6, q, 3H; 2.55, s, 3H; 1.35, t, 2H; MS (DCI/NH3) m/z 187 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In acetonitrile; at 70℃; for 1.5h; | [00158] A solution of ethyl 2-aminothiazole-4-methyl-5-carboxylate as a (210 mg, 1.13 mmol) and 5-(methoxymethylene)-2,2-dimethyl-l,3-dioxane-4,6-dione as b (213 mg, 1.13 mmol) in MeCN (3 mL) was heated at 700C for 90 min. The solution was then cooled to room temperature and the MeCN removed in vacuo. Ether (5 mL) was added then hexane (2 mL) and the resulting slurry stirred for 5 min then filtered. The solids were washed with hexane (2 x 3 mL) and dried on a filter to give c as a tan solid (231 mg, 60% yield). HPLC tR= 3.66 min, 96 % purity; LCMS 341.1 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With polyethylene glycol (PEG-400); In water; for 0.116667h;Microwave irradiation; Green chemistry; | To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles. |
32% | In ethanol; at 95℃; for 14h; | 2-Bromo-1-(4-fluoro-phenyl)-ethanone (200 mg, 0.92 mmol) and 2-amino-4-methyl- thiazole-5-carboxylic acid ethyl ester (186.2 mg, 0.92 mmol) were heated in 5 ml of ethanol at 95 0C for 5 hours. After addition of 80 mg of 2-bromo-1-(4-fluoro-phenyl)- ethanone and further heating for 9 hours at 95C the mixture was evaporated. Addition of potassium hydrogensulfate solution, extraction with ethyl acetate and purification by preparative HPLC (RP18, acetonitrile/water 0.1 % TFA) yielded 81 mg (32%) of the desired product. MS (mass spectrum): M+H+ = 305.07. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | PREPARATION 3; Preparation of (Zf)-ethyl 2-(3-(l-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate; To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate ( 1.86 g, 10.0 mmol) in tetrahydrofuran (50 mL) was added l.l '-carbonyldiimidazole ( 1.95 g, 12.0 mmol) at ambient temperature. The resulting reaction mixture was stirred at ambient temperature for 17 hours, followed by the addition of (7?)-(+)-2-amino-3-phenyl-l- propanol (2.00 g, 13.2 mmol). The reaction mixture was kept stirring at ambient temperature for 50 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate (200 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford the title compound in 88% (3.20 g): MS (ES+) nvz 364.4 (M + 1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | To a 2-neck round bottom flask (1 L) equipped with a mechanical stirrer was added ethyl 2-amino-4-methylthiazole-5-carboxylate (30.00 g, 161.00 mmol) in anhydrous tetrahydrofuran (750 ml_) and pyridine (191.10 g, 242.00 mmol), followed by the dropwise addition of 4-nitrophenyl chloroformate (40.60 g, 202.00 mmol) in anhydrous dichloromethane (100 mL) at 0 C. The yellow reaction mixture was stirred at 0 C for 2 h, followed by the addition of hydrazine monohydrate (25.50 g, 796.00 mmol). The resulting mixture was stirred at ambient temperature for 16 h. The yellow solid was collected by filtration and washed with cold methanol (100 mL) and diethyl ether (100 mL) to afford ethyl 2-(hydrazinecarboxamido)-4-methylthiazole-5-carboxylate as a yellow solid in quantitative yield (42.00 g): mp 225-230 C; 1H NMR (300 MHz, DMSO-c/6) 5 7.24 (brs, 4H), 4.21 (t, J = 7.1 Hz, 2H), 2.48 (s, 3H), 1.26 (t, J =7.1 Hz, 3H); 13C NMR (75 MHz, DMSO-de) 8 162.6, 156.8, 156.3, 156.3, 60.7, 17.5, 14.7; MS (ES+) m/z 245.0 (M + 1). | |
78% | PREPARATION 6; Preparation of ethyl 2-(hydrazinecarboxamido)-4-methylthiazole-5-carboxylate; To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (0.50 g, 2.68 mmol) and pyridine (0.32 mL, 4.03 mmol) in tetrahydrofuran (25 mL) and dichloromethane (25 mL) was added 4-nitrophenyl chloroformate (0.65 g, 3.22 mmol) at 0 0C. The resulting reaction mixture was stirred at ambient temperature for 1 hour, followed by the addition of hydrazine monohydrate (3.00 mL, 59.9 mmol). The reaction mixture was stirred at ambient temperature for 18 hours and quenched with water ( 100 mL). The solid precipitated was filtered, washed with water and ethyl acetate and dried to afford the title compound in 78% yield (0.51 g): MS (ES+) m/z 245.2 (M + 1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | EXAMPLE 3; Synthesis of ethyl 4-methyl-2-(2-oxoimidazolidin-l-yl)thiazole-5-carboxylate; To a solution of ethyl 2-aιnino-4-ιnethylthiazole-5-carboxylate (9.31 g, 49.99 minol) in tetrahydrofuran (200 rnL) was added 2-chloroethyl isocyanate (5.50 rnL, 64.0 minol) at ambient temperature. The resulting reaction mixture was heated to reflux for 7 hours, followed by the addition of potassium carbonate (8.30 g, 60.0 mmol) and tetra-ϖ- butylammonium iodide (0.50 g, 1.35 mmol) and the resulting mixture was heated to reflux for 23 hours. The solvent was removed in vacuo, and the residue was washed with water (200 mL) and ethyl acetate (50 mL) to afford the title compound in 71% yield (9.10 g): mp 197-199 0C; 1H NMR (300 MHz, DMSCW6) δ 7.83 (s, I H), 4.20-3.93 (m, 4H), 3.49-3.43 (m, 2H), 2.46 (s, 3H), 1.20 (t, J = 6.9 Hz, 3H); MS (ES+) m/z 256.3 (M + 1 ). | |
71% | To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (9.31 g, 49.99 mmol) in tetrahydrofuran (200 ml_) was added 2-chloroethyl isocyanate (5.50 ml_, 64.0 mmol) at ambient temperature. The resulting reaction mixture was heated to reflux for 7 hours, followed by the addition of potassium carbonate (8.30 g, 60.0 mmol) and tetra-n-butylammonium iodide (0.50 g, 1.35 mmol) and the resulting mixture was heated to reflux for 23 hours. The solvent was removed in vacuo, and the residue was washed with water (200 ml_) and ethyl acetate (50 ml_) to afford the title compound in 71% yield (9.10 g): mp 197-199 C; 1H NMR (300 MHz, DMSO-d6) 8 7.83 (s, 1H), 4.20-3.93 (m, 4H), 3.49-3.43 (m, 2H), 2.46 (s, 3H), 1.20 (t, J = 6.9 Hz, 3H); MS (ES+) m/z 256.3 (M + 1)- |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With hypophosphorous acid; sodium nitrite; In water; at -5 - 20℃; for 3h; | Compound 3a (4.0 g, 21.5 mmol) was dissolved in 106 ml of 30% H3PO2.Cool to -5 C,NaNO2 (3.0 g, 2.0 eq) was dissolved in 12 ml of water.Add dropwise to the reaction solution,After the addition is completed,Transfer to 0 C for 1 h, stir at room temperature for 2 h,Cold NaOH (17g, dissolved in 200ml water) is slowly added dropwise.Saturated NaHCO3 solution is neutral,Extracted with Et2O (50mlx3),Column chromatography (PE: EA=50:1v/v),A yellow semisolid 3b (2.1 g, 56%) was obtained. |
Thiazoles (1b-f, j) were prepared from 2-aminothiazoles according to the reported procedure with slight modifications. 24 To a mechanically-stirred solution of 2-amino-6-chlorobenzothiazole (4 g, 21.7 mmol, 1.0 equiv) in 84% aq phosphoric acid (80 mL) was added a solution of sodium nitrite (9.0 g, 13 mmol, 6.0 equiv) in water (28 mL) dropwise below the surface at -10 C. After stirring at -10 C for another 2 h, a 50% aq solution of hypophosphorous acid (60 mL) was added dropwise to the resulting thick syrup mixture at -5 C. The reaction mixture was warmed to room temperature, stirred overnight, and then diluted with water (300 mL). Na2CO3 was added portionwise to adjust to pH=8 and extracted with DCM. The organic phase was dried over Na2SO4, concentrated under vacuum, and purified over column chromatography (petroleum ether/EtOAc=100:1) to give 6-chlorobenzothiazole as white solid (2.2 g, 59% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In N,N-dimethyl-formamide; at 0 - 20℃; for 18h; | To a stirred cold (0 C) solution of 1-fluoro-2-nitrobenzene (1.00 g, 7.13 mmol) in /V,/V-dimethylformamide was added ethyl 2-amino-4-methylthiazole-5-carboxylate (2.00 g, 10.7 mmol). The cold bath was removed after 1 h, and the mixture was stirred at ambient temperature for 17 h. The mixture was concentrated in vacuo. The residue was diluted with dichloromethane (150 ml_) and washed with saturated aqueous ammonium chloride (2 x 25 ml_), water (3 x 20 ml_), dried over sodium sulfate, and filtered. The filtrate was concentrated and purified by column chromatography eluted with hexanes/ethyl acetate to give 4-methyl-2-(2-nitrophenylamino)thiazole-5-carboxylate as an orange solid (1.45 g, yield 67%): 1H NMR (300 MHz, CDCI3) 5 8.66-8.63 (m, 1H), 8.27-8.24 (m, 1H), 7.70-7.64 (m, 1H), 7.13-7.07 (m, 1H), 4.30 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H); MS (ES+) m/z 308.0 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 50℃; for 6h; | A solution of 2-[(1 ,1-dimethylethyl)oxy]carbonyl}-1 ,2,3,4-tetrahydro-6- isoquinolinecarboxylic acid (296 mg, 1.07 mmol), HATU (406 mg, 1.07 mmol), DIPEA (0.41 ml_, 2.36 mmol ) and ethyl 2-amino-4-methyl-1 ,3-thiazole-5-carboxylate (199 mg, 1.07 mmol) in DMF (5 ml.) was stirred at 500C for 6 hours. The volatiles were removed under reduced pressure and the residue was dissolved in ethyl acetate. The organic phase was then washed with dilute HCI, with a solution of sodium bicarbonate, dried over MgSO4, filtered and evaporated under reduced pressure. The residue was dissolved in a mixture of ethanol (1.5 ml.) and water (2 ml.) and sodium hydroxide was added (86 mg, 2.15 mmol) and the reaction mixture was heated at 500C for 4 hours. The reaction was then cooled, acidified with dilute HCI and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried over MgSO4, filtered and evaporated under reduced pressure. The residue obtained was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (10 g, 0.05 mol) in MeCN (100 mL) was added p-toluenesulfonic acid monohydrate (20.4 g, 0.107 mol) and the reaction mixture was stirred at1792 HETEROCYCLES, Vol. 100, No. 11, 2020 room temperature for 4 h. The mixture was cooled to 0 C, followed by addition of aqueous solution of NaNO2 (5.5 g, 0.080 mol) and KI (13.36 g, 0.080 mol) in water (25 mL), maintaining temperature below 0 C. The reaction mixture was further stirred for 24 h at room temperature followed by addition of aqueous sodium metabisulphate and was extracted with EtOAc (5 x 100 mL). The combined organic layers were dried over anhydrous Na2SO4, the solvent evaporated in vacuum which gave pale yellow solid, yield 72%; mp 175 C. IR (ATR, cm-1): = 1711 (C=O); 1H NMR (DMSO-d6, δ, ppm): 4.29-4.22 (q, J = 7.1 Hz, 2H, CH2), 2.62 (s, 3H, CH3), 1.29-1.24 (t, J = 7.1 Hz, 3H, CH3); MS m/z (%): 297 (M+), 296.93 (100.0), 297.94 (7.7), 298.93 (4.6), 297.93 (1.2); Anal. Calcd (%) for C7H8INO2S: C, 28.30; H, 2.71; N, 4.71. Found: C, 28.53; H, 2.77; N, 4.79 | |
With sulfuric acid; copper(II) sulfate; sodium iodide; sodium nitrite; In water; at -8 - 8℃; for 1.5h; | Step 2: Ethyl 2-iodo-4-methyl-l,3-thiazole-5-carboxylate; A slurry of ethyl 2-amino-4-methyl-l,3-thiazole-5-carboxylate (11.4 g, 61.21 mmoles) and a solution of NaI (2 eq) in water (80 mL) was added to a stirred solution at -8 0C of CuSO4 (1.5 eq) and H2SO4 (175 mL) in water (425 mL). A solution OfNaNO2 (1.9 eq) in water (25 mL) was added beneath the surface of the mixture for 30 min and the mixture was allowed to warm to 8 0C for 1 h. The reaction mixture was then extracted with diethyl ether and the organic layer was then dried over Na2SO4 and concentrated to get 6.5 g of the desired product. 1H NMR (CDCl3) δ 4.28-4.21 (q, J= 6.9 Hz, 2H)5 2.63 (s, 3H), 1.27 (t, J= 6.9 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; at 20℃; | General Procedure: To the residue was added dry tetrahydrofuran (THF, 1.5 ml). It was added dropwise to a solution of n-buthyllithium (0.80 mmol, 1.6 M in n-Hexane) deprotonated amine (0.80 mmol) in 1.5 ml tetrahydrofuran and stirred at room temperature overnight. The reaction solution was added to a vigorous stirred water to give the solid crude urea. The solid was filtered off and recrystallised from methanol or ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; at 20℃; | General Procedure: To the residue was added dry tetrahydrofuran (THF, 1.5 ml). It was added dropwise to a solution of n-buthyllithium (0.80 mmol, 1.6 M in n-Hexane) deprotonated amine (0.80 mmol) in 1.5 ml tetrahydrofuran and stirred at room temperature overnight. The reaction solution was added to a vigorous stirred water to give the solid crude urea. The solid was filtered off and recrystallised from methanol or ethanol. |
Tags: Ethyl 2-amino-4-methylthiazole-5-carboxylate | EMTC | Thiazoles | Amines | Esters | Organic Building Blocks | Heterocyclic Building Blocks | 7210-76-6
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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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