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Structure of 2032-35-1
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CAS No. : | 2032-35-1 |
Formula : | C6H13BrO2 |
M.W : | 197.07 |
SMILES Code : | CCOC(OCC)CBr |
MDL No. : | MFCD00000214 |
InChI Key : | LILXDMFJXYAKMK-UHFFFAOYSA-N |
Pubchem ID : | 74852 |
GHS Pictogram: | ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H315-H319-H330 |
Precautionary Statements: | P260-P264-P271-P302+P352-P304+P340+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.0 |
TPSA ? Topological Polar Surface Area: Calculated from | 18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.59 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 1.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.8 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.73 |
Solubility | 3.64 mg/ml ; 0.0185 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.59 |
Solubility | 5.08 mg/ml ; 0.0258 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.25 |
Solubility | 1.1 mg/ml ; 0.00556 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 | -6.37 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 | 2.0 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) | 2.87 |
* 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 |
---|---|---|
2.77 g | Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 15 h; Stage #2: at 175℃; for 0.75 h; | 12116] Step 112117] A mixture of 5.2 g ofbromoacetaldehyde diethylacetal and 10 ml of tetrahydrofuran was added to a mixture of 4.00 g of 4-methylbenzenethiol, 1.4 g of 60percent sodium hydride, and 35 ml of tetrahydroffiran. The reaction mixture was stirred for 15 hours at room temperature. Ten (10) ml of aqueous saturated ammonium chloride solution was added to the reaction mixture, and extraction was performed three times by using tert-butyl methyl ether. The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The residues were added to a mixture of 5 g of diphosphorus pentoxide and lOg ofphosphoric acid that had been stirred for 45 minutes at 175° C., and the residue was stirred for 5 minutes. The reaction mixture was poured into ice water, and extraction was performed three times by using tert-butyl methyl ethet The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The residues were subjected to silica gel colunm chromatography, thereby obtaining 2.77 g of 5-methylbenzo[b] thiophene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.6% | Stage #1: With hydrogenchloride In ethanol at 20℃; Reflux Stage #2: at 20℃; | In a 250 mL single-necked flask, bromoacetaldehyde diethyl acetal (42.5 g, 215.7 mmol) was dissolved in 1 mol / L HCL(120 mL) and ethanol (20 mL), stirred at room temperature for 30 min, heated to reflux, stirred until the solution was clear, cooled to room temperature,Add NaHCO3 adjusted to near neutral,2-Amino-5-nitropyridine (15.0 g, 107.8 mmol) was added and reacted at room temperatureovernight. The reaction was completed, extracted with ethyl acetate (100mL × 3), the organic phase was collected and the solvent was evaporated to dryness under reduced pressure. The residue was passed through a silica gel column (PE:EA = 2: 1) to give 13.7 g of 6-nitroimidazo [1,2-a] pyridine yellow-brown crystals in a yield of 77.6percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium carbonate; at 120℃; for 16.0h; | Example 28 - Preparation of Cmpd 23; [0206] A useful scheme for the preparation of compounds of the type of Cmpd 23 is provided in Scheme 2 following. Scheme 2Intermediate 7 Intermediate 8Cmpd 23 Intermediate 9[0207] A detailed description of the preparation of Intermediates 7-9 and Cmpd 23 follows. Preparation of Intermediate 7Intermediate 7[0208] A mixture of 2-bromoacetaldehyde diethyl acetal (4.5 g, 22.9 mmol), morpholine (2.0 g, 22.9 mmol) and K2C03 (6.34 g, 45.9 mmol, 2 eq) was stirred at 120 C for 16 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with DCM (3 x 50 mL). The organic layer was washed with saturated aqueous NaHC03 (50 mL), brine (50 mL), dried over Na2S04, filtered and concentrated to get crude a residue. The crude compound was purified by column chromatography over silica gel (100-200 mesh) by using a gradient mixture of 0-50% EtOAc-hexane as the eluent to afford Intermediate 7 (2.6 g, 56%) as a pale yellow liquid. 1H NMR: (CDC13) delta 4.64 (t, J= 5.3 Hz, 1H), 3.63-3.70 (m, 6H), 3.50-3.58 (m, 2H), 2.52-2.55 (m, 6H), 1.20 (t, J= 7.0 Hz, 6H); TLC: 60% EtOAc in hexane: Rf: 0.50. |
56% | With potassium carbonate; at 120℃; for 16.0h; | A mixture of 2-bromoacetaldehyde diethyl acetal (4.5 g, 22.9 mmol), morpholine (2.0 g, 22.9 mmol) and K2CO3 (6.34 g, 45.9 mmol, 2 eq) was stirred at 120C. for 16 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with DCM (350 mL). The organic layer was washed with saturated aqueous NaHCO3 (50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to get crude a residue. The crude compound was purified by column chromatography over silica gel (100-200 mesh) by using a gradient mixture of 0-50% EtOAc-hexane as the eluent to afford Intermediate 7 (2.6 g, 56%) as a pale yellow liquid. 1H NMR: (CDCl3) delta 4.64 (t, J=5.3 Hz, 1H), 3.63-3.70 (m, 6H), 3.50-3.58 (m, 2H), 2.52-2.55 (m, 6H), 1.20 (t, J=7.0 Hz, 6H); TLC: 60% EtOAcin hexane: Rf: 0.50. |
14% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 5.0h; | Synthesis of compound 62.2. Morpholine (2.0g, 2.19mmol, l .Oeq), bromoacetaldehyde diethyl acetal (4.5g, 2.54mmol, 1.16eq) and dry K2CO3 (6.04g, 4.38mmol, 2.0 eq) were mixed in dry dimethylformamide and heated at 120 C for 5h. After completion of reaction, reaction mixture was diluted with ethyl acetate (200ml) and washed with water (200ml x2) and then with brine (100ml). Organic layer was dried over sodium sulphate and concentrated under reduced pressure at 45C. Crude was purified by column chromatography to afford compound 62.2 (0.650g, 14%). 1H NMR (400 MHz, CDC13): delta 4.660-4.686 (t, 1H), 3.686-3.738 (m, 6H), 3.528-3.3.581 (m, 2H), 3.554-3.577 (t, 6H), 1.216-1.252 (t, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; sodium iodide; at 145℃; for 4h; | Method AI: Ethyl 2-cyano-4,4-diethoxybutanoate (xlii-a):_ 2-Bromo-1,1-diethoxyethane (4 g, 20 mmol, 1.0 eq.) was added to a mixture of ethyl 2-cyanoacetate (11.4 g, 101 mmol, 5.0 eq.), K2CO3 (2.8 g, 20 mmol, 1.0 eq.) and NaI (200 mg, 1.3 mmol, 0.06 eq.), as described in J. Chem. Soc., 1960, 131-138. The reaction mixture was refluxed for 4 h at 145 C. After cooling, the reaction mixture was purified by chromatography on silica gel (eluted with petroleum ether/ethyl acetate (80:1?40:1?40:1) to give 3.57 g of xlii-a as a colorless oil (78%). 1H NMR (400 MHz, CDCl3): delta 4.70 (t, J=5.6 Hz, 1H), 4.26 (q, J=7.2 Hz, 2H), 3.78-3.64 (m, 3H), 3.62-3.45 (m, 2H), 2.35-2.14 (m, 2H), 1.34 (q, J=7.2 Hz, 3H), 1.25-1.16 (m, 6H). |
78% | With potassium carbonate; sodium iodide; at 145℃; for 4h; | As described in J. Chem. Soc., 1960, 131-138,2-Bromo-1,1-diethoxyethane (4 g, 20 mmol, 1.0 eq)Was added to a mixture of ethyl 2-cyanoacetate (11.4 g, 101 mmol, 5.0 eq), K 2 CO 3 (2.8 g, 20 mmol, 1.0 eq) and NaI (200 mg, 1.3 mmol, 0.06 eq) .The reaction mixture was refluxed at 145 C. for 4 hours.After cooling, the reaction mixture was purified by silica gel chromatography (eluting with petroleum ether / ethyl acetate (80: 1 ? 40: 1 ? 10: 1)) to give 3.57 g of xlii-a as a colorless oil I got it (78%). |
74% | With potassium carbonate; sodium iodide; at 145℃; for 4.5h;Inert atmosphere; | To a dry 3-necked round bottomed flask fitted with a condenser was added 11.3 g (81.5 mmol) of oven dried K2CO3 and 0.82 g (5.5 mmol) of NaI. The solids were placed under high vacuum for an hour to ensure dryness. The flask was refilled with argon and 44.0 mL (0.413 mol) of ethyl cyanoacetate was added followed by 13.0 mL (83.8 mmol) of bromoacetal. The yellow mixture was heated to 145C for 4.5 hours and was then cooled to room temperature. The mixture was dissolved in 100 mL of water and 100 mL of diethyl ether. The organic layer was separated and the aqueous layer was extracted with an additional 100 mL of ether. The organic layers were dried over MgSO4, filtered, and concentrated. The crude material was purified by column chromatography (9:1 Hex/EtOAc) to give 14.2 g (62.0 mmol, 74% yield) of a light yellow oil. (Rf: 0.53; 1:1 Hex/EtOAc). 1H-NMR (CDCl3, 600 MHz): ? 1.18 - 1.22 (m, 6H), 1.31 (t, 3H, J = 7.2 Hz), 2.16 - 2.21 (m, 1H), 2.24 - 2.29 (m, 1H), 3.49 - 3.55 (m, 2H), 3.64 - 3.71 (m, 3H), 4.24 (q, 2H, J = 7.2 Hz), 4.68 (t, 1H, J = 5.4 Hz). 13C-NMR (CDCl3, 150 Mz): ? 14.1, 15.3, 33.7, 62.8, 62.9, 100.1, 116.5, 166.0. HRMS (FAB): expected for C11H20NO4 (M+H)+: 230.13868. Found: 230.13861. IR(neat): vmax 2989, 1774 cm-1. |
70% | With sodium methylate; In N,N-dimethyl-formamide; at 90℃; for 4h; | The synthesis of target compound 3 (Scheme 1C), started with the synthesis of a reported method for compound i.?3 2-Bromo-i,i-diethoxyethane (compound 10) was reacted with ethyl2-cyanoacetate to obtain compound 1 lwhich was cyclized to compound 12 using acetamidine hydrochloride under basic conditions. Chlorination of compound 12 using POC13 provided compound 13 in 80% yield. Displacement of the chloride of compound 13 with 4-methoxy-N- methyl aniline (compound 14) and catalytic amounts of HC1 in isopropanol, provided compound1. Methylation of compound 1 with Mel under basic conditions afforded compound 3 in 85% yield. The synthesis of target compound 5 (Scheme 1C), involved N-formylation of 4-methoxy- 2-methylanline (compound 15) to afford compound 16 in 70% yield. LAH reduction of compound 16 provided substituted aniline compound 17. Displacement of the chloride of compound 13 with anilines (compounds 15 and 17) and catalytic amounts of HC1 in isopropanol provided compounds 4 and 5 (75% and 70% respectively). |
70% | With potassium carbonate; In N,N-dimethyl-formamide; at 150℃; | The 113 g (1mol)Ethyl cyanoacetate and 98.5 g (0.5 mol)Bromo acetal is dissolved in 450 g of DMF,Add 138 grams (1 mol) of potassium carbonate,Warm up to about 150 degrees, after the reaction is over,Cool to about 20 degrees and add 450 grams of water.Extracted twice with 500 g of chloroform,Wash once with saturated brine and dry.Vacuum distillation,78.1 g of ethyl 2-cyano-4,4-diethanolbutanoate were obtained in a yield of 70%. |
63% | With potassium carbonate; sodium iodide;Reflux; | Example A1; Preparation of 4-chloro-5-iodopyrrolo[2,3-d]pyrimidine in Accordance with the Following Reaction Scheme; (a) 130 ml (860 mmol) of bromoacetaldehyde diethyl acetal are refluxed for 10 h with ethyl cyanoacetate (430 ml, 4.04 mol), sodium iodide (8.1 g; 54.04 mmol) and potassium carbonate (115.9 g; 839 mmol). After cooling to room temperature (RT), the batch is stirred with 800 ml of water, the aqueous phase is extracted with diethyl ether, the combined organic phases are dried and evaporated. Chromatography gives 124.99 g (63%) of a colourless liquid ethyl 2-cyano-4,4-diethoxybutyrate. |
60% | To a suspension of NaH (60% dispersion in mineral oil, 1.62 g, 40.5 mmol) in DMF (35 mL) and benzene (12 mL) was added ethyl cyanoacetate (4.7 mL, 44.2 mmol) dropwise at -10 0C. After stirring for 1 hour at room temperature, 2-bromo-1 ,1-diethoxyethane (5.6 mL, 0.82 equiv.) was added and the reaction mixture was heated at 100 0C for 2 hours. The reaction mixture was then cooled to room temperature and filtered. The filtrate was condensed, and water was added. The mixture was extracted with ether. The extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (20% EtOAc/hexanes). The desired product was obtained as colorless oil (5 g, 60%). MS: (M + Na)/z = 252. | |
60% | Take a 500 mL two-necked flask and ethyl cyanoacetate (50 g, 0.44 mol) in anhydrous DMF(N, N-dimethylformamide) (300 mL) was added sodium ethoxide (36 g, 0.528 mol, 1.2 eq.) And sodium iodide (catalytic amount) at room temperature Stirring for 30min,2-Bromo-1,1-diethoxyethane was added(66.5 mL, 0.44 mol, 1 equiv)The temperature was raised to 90 C and stirred for 4 h. Cooled to room temperature, evaporated under reduced pressure to remove most of the DMF, add EA (ethyl acetate), stirring 10min, filter, take the filtrate to add saturation Salt water extraction. The organic phase was collected, dried, dried and dried (PE: EA = 12: 1, i.e., the volume ratio of petroleum ether: ethyl acetate was12) was obtained as a pale yellow oily product (61.3 g) in 60% yield. | |
57% | With potassium carbonate; sodium iodide; at 140 - 150℃; | 2-Cyano-4,4-diethoxy-butyric acid ethyl ester (4).; Bromoacetaldehyde diethylacetal (3, 541 g, 2.75 mol) was added to a suspension of powdered potassium carbonate (379.6 g, 2.75 mol, 1.0 equiv) and sodium iodide (33 g, 0.22 mol, 0.08 equiv) in ethyl cyanoacetate(2, 1.55 Kg, 13.75 mol, 5.0 equiv). Upon addition of the aldehyde to the reaction mixture, the resulting solution turned yellow. The reaction mixture was slowly heated to 140-150 C. collecting the volatile material in a Dean Stark trap. This material was discarded. Fairly vigorous gas evolution was observed to begin at 140 C. The reaction was monitored by G.C. and was observed to be near completion at 90 minutes. Heating was continued for an additional 45 minutes when gas evolution was observed to have ceased. The reaction mixture was then cooled to room temperature and partitioned between 4 L water and 2 L methyl tent-butyl ether (MTBE). The layers were separated and the aqueous layer was extracted with an additional 2 L of MTBE. The aqueous layer was checked for product by G.C. then discarded. The organic layers were dried over sodium sulfate, filtered and concentrated in vacuum. The crude product was purified by fractional distillation (91-105 C. (at) 0.53-0.65 mm/Hg) to afford 2-cyano-4,4-diethoxy-butyric acid ethyl ester (4, 359.4 g, 630.5 g theoretical, 57%) as a oil. For 4: 1H NMR (DMSO-d6, 300 MHz) delta ppm 4.60 (t, 1H, J=5.6 Hz), 4.15 (m, 3H), 3.59 (m, 2H), 3.45 (m,1H), 2.11 (t, 2H, J=6.2 Hz), 1.22 (t, 3H, J=6.9 Hz), 1.10 (dt, 6H, J=7.1, 6.9 Hz). |
51.0% | With potassium carbonate; sodium iodide; for 24h;Reflux; | Preparation of intermediate compound (87) a. A mixture of ethyl cyanoacetate 81 (227.97 g, 2015.52 mmol), bromo acetaldehyde diethyl ether (80) (80 g, 405.94 mmol), potassium carbonate (55.99 g, 405.13 mmol) and sodium iodide (4 g, 26.67 mmol) was refluxed for 20 h (CO2 evolution was observed during the reaction). The reaction mixture was stirred at reflux for additional 4 h after the evolution of CO2 has ceased. The reaction was cooled to room temperature, diluted with water (400 mL) and diethyl ether (400 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (250 mL). The ether layers were combined washed with water (2 x 100 mL), brine (200 mL), dried, filtered and concentrated in vacuum. The product obtained was distilled under vacuum to furnish ethyl-2- cyano-4, 4-diethoxybutanoate (82) (47.5 g, 51.0 %) as a colorless oil; B.P: 103 C/1 mm Hg. 1HNMR (300 MHz, DMSO) delta 4.61 (t, J= 5.7, IH), 4.24 - 4.08 (m, 3H), 3.67 - 3.54 (m, 2H), 3.53 - 3.40 (m, 2H), 2.12 (t, J= 6.0, 2H), 1.23 (t, J= 7.1, 3H), 1.11 (td, J= 4.9, 7.0, 6H); IR (neat): 3482, 2980, 2901, 2361, 2252, 1749, 1446, 1374, 1262, 1218, 1128, 1062 and 857 cm"1; MS (ES"): 263.6 (M + 35); Analysis: CaIc for CnHi9NO4.0.25 H2O: C, 56.51; H, 8.40; N, 5.99; Found: C, 56.71; H, 8.16; N, 5.96. |
29.2% | With potassium carbonate; potassium iodide; for 12h;Reflux; | Step 5: Preparation of ethyl 2-cyano-4,4-diethoxybutanoate A mixture of ethyl 2-cyanoacetate (1000 g, 8.84 mol), 2-bromo-1,1-diethoxyethane (400 g, 2.03 mol), KI (33.4 g, 0.201 mol) and K2CO3 (280 g, 2.03 mol) was heated to reflux for 12 hrs. The reaction mixture was diluted with CH2Cl2 (1000 mL) and the resulting precipitate was filtered off and the filtrate was washed with brine and dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue distilled to give the title compound (136 g, 29.2% yield) as a light yellow oil that was used as is in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | A suspension of 2-amino-5-bromopyrimidine (3.0 g, 17.2 mmol), bromoacetaldehyde diethyl acetal (3.2 mL, 20.7 mmol) and 48% HBr (1.7 mL) in EtOH was heated was heated to 80 0C in a sealed tube for 16 h. After cooling to rt, the reaction was adjusted to pH ~12 with 6N NaOH and the resultant precipitate was collected by filtration, rinsed with water followed by hexanes and dried to a constant weight to give 2.12 g (62%) of 6-bromoimidazo[l,2-alpha]pyrimidine as a white solid. MS(ES)+ m/e 199.7 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | To a suspension of sodium hydride (3.0 g, 60percent dispersion in mineral oil, 125 [MMOL)] in xylenes under nitrogen was added 2, 2-diethoxy-ethanol (15.3 g, 114 [MMOL)] dropwise via canula. The reaction was heated to reflux for two hours, cooled to ambient temperature followed by addition of 2-bromo-1,1-diethoxy-ethane (25.6 mL, 170 [MMOL)] dropwise. The reaction was then heated at reflux overnight. The xylenes were distilled off under atmospheric pressure. The title compound was distilled off under vacuum (6 mm Hg) at [120°C] (12.0 grams, 42 percent yield) | |
33% | To a suspension of NaH (60percent dispersion in mineral oil, 3.8 g, 95.0 mmol) in xylene (100 mL) was added 2,2-diethoxyethanol (1 1.6 g, 86.4 mmol) under N2. The mixture heated at 1 10 °C for 2 hours, then cooled to room temperature and 2-bromo-1 ,1 -diethoxyethane (25.6 g, 130.0 mmol) added. The reaction was heated at 1 10 °C overnight, then cooled to room temperature and the organic layer washed with water, dried (Na2S04), filtered and concentrated. The residue obtained was purified by distillation to give the title compound (7 g, 33percent) as colorless oil. | |
With potassium iodide; In tetrahydrofuran; diethyl ether; water; mineral oil; | Stage I Hydroxyacetaldehyde diethylacetal (3.75 g) was added to sodium hydride (0.8 g, 80percent in mineral oil) in tetrahydrofuran (100 ml) under an atmosphere of nitrogen. The mixture was stirred and bromoacetaldehyde diethyl acetal (5.0 g) and potassium iodide (0.1 g) were added. The mixture was heated to reflux for 16 hours, water added and evaporated under reduced pressure. The residue was dissolved in diethyl ether, the organic phase washed with water, dried (MgSO4) and evaporated under reduced pressure to give bis(2,2-diethoxyethyl)ether, 3.43 g, as a yellow oil. 1 H NMR (CDCl3): delta 1.20(12H,t); 3.60(8H,d); 3.70(4H,q); 4.60(2H,t)ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium hydrogencarbonate; In N,N-dimethyl-formamide; for 72h;Heating / reflux; | Synthesis of (3-Bromo-5-methoxy-phenyl)-(2,2-diethoxy-ethyl)-amine (CXI) A solution of 3-Bromo-5-methoxy-phenylamine CX (4.0 g, 20 mmol), bromoacetaldehyde diethyl acetal (3.1 ml, 20 mmol) and NaHCO3 (1.8 g, 21 mmol) in DMF (25 ml) was stirred at reflux for 72 hours. The mixture was cooled to room temperature and the solvent was partially evaporated. The residue was dissolved in Et2O (100 ml), washed with H2O (50 ml) and brine (25 ml), dried over Na2SO4, filtered, concentrated, and purified via flash chromatography (hexane/EtOAc) affording the compound CXI as a yellow oil (4.8 g, 75% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 150℃; for 2h; | General procedure: A solution of methyl-4-hydroxy indole carboxylate 34 (2.5 g, 13.1 mmol) in DMF (50 mL) was treated with Cs2CO3 (5.12 g, 15.72 mmol), bromoacetaldehye diethyl acetal (12.90 g, 65.6 mmol) and stirred at reflux for 2 h. The reaction mixture was cooled to room temperature, treated with aq NaOH (1 M, 50 mL) and extracted into EtOAc (250 mL). The organic layers were dried (MgSO4), filtered, concentrated in vacuo (high vacuum to distill out DMF and bromoacetaldehyde) and purified by chromatography (SiO2, hexanes/EtOAc 0 ? 100%) to yield methyl 4-(2,2-diethoxyethoxy)-1H-indole-2-carboxylate 35 (3.5 g, 88%). | |
With caesium carbonate; In N,N-dimethyl-formamide; for 2h;Heating / reflux; | Example 3; Preparation of Compound 9; Step A - Synthesis of Compound 9A; To a solution of 5-hydroxy-lH-indole-2-carboxylic acid ethyl ester (5.00 g, 25.00 mmol) in DMF (30 mL) was added Cs2CO3 (9.00 g, 1.1 mmol) and bromoacetaldehyde- diethylacetal (20 g, 5.00 mmol) and the resulting reaction was allowed to stir at reflux for 2 hours. The reaction mixture was cooled to room temperature, treated with aqueous NaOH (IM, 500 mL) and extracted into EtOAc (500 mL). The organic layers were dried (MgSO4), filtered, concentrated in vacuo (high vacuo to distill out DMF and bromoacetaldehyde) and purified using flash column chromatography (etaexanes/EtOAc, 0 to 100%) to provide compound 9A as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; at 150℃; for 2h;microwave irradiation;Product distribution / selectivity; | Step A: Preparation of Imidazo[l,2-alpha]pyridine-8-carboxylic Acid.2-Aminonicotinic acid (2.0 g, 14.48 mmol) and 2-bromo-l,l-diethoxyethane (2.247 mL, 14.48 mmol) in acetonitrile (10 mL) were heated at 150 0C for 2 h under microwave irradiation. The resulting precipitate was filtered off and washed with acetonitrile and hexane to afford the title compound (2.783 g) as a solid. Exact mass calculated for C8H6N2O2: 162.0. Found: LCMS mlz = 163.1 (M + H)+. 1H NMR (400 MHz, Methanol-^) delta 7.62 (dd, J = 6.82, 7.33 Hz, IH), 8.06 (d, J = 2.27 Hz, IH), 8.36 (d, J = 2.02 Hz, IH), 8.62 (d, J = 7.33 Hz, IH), 9.04 (d, J = 6.82 Hz, IH). Step B: Preparation of 3-Bromoimidazo[l,2-alpha]pyridine-8-carboxylic Acid.Imidazo[l,2-alpha]pyridine-8-carboxylic acid (100 mg, 617 mumol), l-bromopyrrolidine-2,5- dione (110 mg, 617 mumol) and N,N-dimethylformamide (1.5 mL) were stirred at room temperature for 1 h. The resulting precipitate was filtered off and washed with acetonitrile and hexane to afford the title compound as a solid (68 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Intermediate 2: 5,8-Dibromo-imidazo[1,2-a]pyrazine Bromoacetaldehyde diethyl acetal (49 mL, 326 mmol) and 48% hydrobromic acid is heated to reflux for 1.5 h, then poured into propan-2-ol (600 mL) and quenched with NaHCO3. After filtering, 3,6-dibromopyrazin-2-yl amine (41.34 g, 163 mmol) is added to the solution and heated at reflux overnight. The reaction is cooled and solvents removed in vacuo, followed by addition of aq. NaHCO3 and extraction with EtOAc. The organic phase is dried over anhydrous MgSO4, filtered, and concentrated in vacuo to afford a brown solid. 1H NMR (250 MHz, CDCl3) delta (ppm) 7.86 (s, 1H), 7.93-7.94 (d, 1H), 7.98-7.99 (d, 1H); m/z (APCI) 278 (M+H)+; m.p 132-135 C. | ||
2.75 g | In tetrahydrofuran; water; at 120℃; for 4h; | <strong>[957230-70-5]3,6-dibromopyrazin-2-ylamine</strong> (4.0 g, 15.80 mmol) and bromoacetaldehyde diethyl acetal (3.7 mL, 24.00mmol) and tetrahydrofuran (5.3 mL) eere dissolved in distilled water (53 mL), the mixture was stirred for 4 hours at 120C .Saturated aqueous sodium hydrogen carbonate solution to the reaction solution was neutralized by addition. The resulting solid was filtered and washed with distilled water and dried to give the title compound (2.75 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16.0833h; | a) 2-(2-(2,2-diethoxyethoxy)phenyl)ethanol 2-bromo-1,1-diethoxyethane (5.13 g) was added to a stirred mixture of cesium carbonate (8.49 g) and 2-(2-hydroxyethyl)phenol (3.00 g) in DMF (20 mL). After 5 minutes the reaction mixture was heated at 80° C. 16h, the reaction mixture was allowed to cool and partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water (*3) then evaporated. Purification by silica gel chromatography eluding with ethyl acetate:iso-hexanes, 1:3 gave the subtitle compound as a green oil. Yield 3.6 g. 1H NMR (400 MHz, CDCl3) delta 7.23-7.10 (m, 2H), 7.95-7.80 (m, 2H), 4.78 (t, J=7.2 Hz, 1H), 4.01 (d, J=7.2 Hz, 2H), 3.90-3.70 (m, 6H), 2.92 (t, J=8 Hz, 2H), 1.98 (t, J=8.0 Hz, 1H), 1.25 (t, J=9.2 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Sodium hydride (60% in oil, 0.36g) was suspended in DMF(10ml) , and was cooled to 0 C in an ice water bath. 5H-Furo[3,2-c]pyridin-4-one(1.0g) was added thereto at the same temperature, and the mixture was stirred at 0 C for an hour. Bromoacetaldehyde diethylacetal (2.6ml) was added thereto, and the mixture was stirred at 80 C for 5 hours. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. A 3N-hydrochrolic acid (5.8ml) was added to an acetone solution (20ml) of the residue, and the liquid was stirred at 60 C for 5 hours. Water was added to the reaction liquid and stirred at room temperature. The precipitated insoluble matter was separated, washed with water, and dried to give the title compound (0.90g) as a white solid. 1H-NMR (DMSO-d6) delta ppm: 3.88 (d, J=5.4 Hz, 2H) , 4.95-5.03 (m, 1H) , 6.08 (d, J=6.4 Hz, 2H) , 6.69 (dd, J=7.4, 0.8 Hz, 1H) , 6.94 (dd, J=2.1 and 0.8 Hz, 1H) , 7.50 (d, J=7.4 Hz, 1H), 7.86 (d, J=2.1 Hz, 1H) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: The suspension of S8-SM (23 g, 124 mmol) and K2C03 (34.3 g, 248 mmol) in DMFwas stirred at 100C for 1 hr, then 2-bromo-1,1-diethoxyethane (21 mL, 155 mmol) was addeddropwise. The reaction mixture was stirred at 100C overnight. The reaction mixture was cooled to room temperature and filtered. The filtrate was poured into water and the mixture was extracted with ethyl acetate. The combined organic layer was washed with water and brine two times respectively, separated, dried over anhydrous sodium sulfate, filtered and concentrated.The obtained residue was purified by chromatography and eluted with petroleum ether: ethyl acetate (60:1) to afford S8-1. ?H NMR (CDC13, 300MHz) oe 6.96-6.95 (m, 2H), 6.92 (s, 1H), 4.83-4.80 (t, J= 5.1 Hz, 1H,) 3.96-3.95 (d, J= 5.4 Hz, 2H), 3.81-3.57 (m, 4H), 2.15 (s, 3H),1.26-1.21 (t, J= 6.9 Hz, 6H). | ||
Step 1: The suspension of S8-SM (23 g, 124 mmol) and K2C03 (34.3 g, 248 mmol) in DMF was stirred at 100 C for 1 hr, then 2-bromo-l,l-diethoxy ethane (21 mL, 155 mmol) was added dropwise. The reaction mixture was stirred at 100 C overnight. The reaction mixture was cooled to room temperature and filtered. The filtrate was poured into water and the mixture was extracted with ethyl acetate. The combined organic layer was washed with water and brine two times respectively, separated, dried over anhydrous sodium sulfate, filtered and concentrated. The obtained residue was purified by chromatography and eluted with petroleum ether: ethyl acetate (60: 1) to afford S8-1. 1H NMR (CDC13, 300MHz) delta 6.96-6.95 (m, 2H), 6.92 (s, 1H), 4.83-4.80 (t, / = 5.1 Hz, 1H,) 3.96-3.95 (d, / = 5.4 Hz, 2H), 3.81-3.57 (m, 4H), 2.15 (s, 3H),1.26- 1.21 (t, / = 6.9 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In tetrahydrofuran; at 20 - 125℃;Inert atmosphere; | A mixture comprising 235 g (931 mmol) <strong>[1206487-35-5]4,6-dibromopyridazin-3-amine</strong> which was prepared according to intermediate example 30g, 421 mL (2792 mmol) 2- bromo-1 ,1 -diethoxyethane, 2.93 L water and 227 mL THF was heated at 125C for for h and at rt overnight. The solution was neutralized by addition of solid NaHC03, the precipitate was filtered off, washed with water and dried to give 156 g (80%) of the title compound as a brownish solid. 1 H-NMR (DMSO-d6): delta= 7.81 (1 H), 8.40 (1 H) ppm. |
80% | In tetrahydrofuran; water; at 20 - 125℃; | A mixture comprising 235 g (931 mmol) <strong>[1206487-35-5]4,6-dibromopyridazin-3-amine</strong> which was prepared according to intermediate example 1g, 421 mL (2792 mmol) 2-bromo-1 ,1 - diethoxyethane, 2.93 L water and 227 mL THF was heated at 125 C for for h and at rt overnight. The solution was neutralized by addition of solid NaHC03, the precipitate was filtered off, washed with water and dried to give 156 g (80%) of the title compound as a brownish solid. 1 H-NMR (DMSO-d6): delta= 7.81 (1 H), 8.40 (1 H) ppm. |
80% | In tetrahydrofuran; water; at 20 - 125℃;Inert atmosphere; | Intermediate Example 26f 6,8-dibromoimidazo[1 ,2-b]pyridazine A mixture comprising 235 g (931 mmol) <strong>[1206487-35-5]4,6-dibromopyridazin-3-amine</strong> which was prepared according to intermediate example 26g, 421 mL (2792 mmol) 2- bromo-1 , 1 -diethoxyethane, 2.93 L water and 227 mL THF was heated at 125C for for h and at rt overnight. The solution was neutralized by addition of solid NaHC03, the precipitate was filtered off, washed with water and dried to give 156 g (80%) of the title compound as a brownish solid. 1 H-NMR (DMSO-d6): delta= 7.81 (1 H), 8.40 (1 H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogen bromide; In isopropyl alcohol; for 2.0h;Reflux; | Preparation of 6-chloro-7,8-dimethylimidazo[1,2-b]pyridazine To a solution of <strong>[76593-36-7]6-chloro-4,5-dimethylpyridazin-3-amine</strong> (2.00 g, 12.7 mmol, 1.0 equiv) in isopropanol (40 mL) was added bromoacetaldehyde diethyl acetal (5.23 mL, 34.8 mmol, 2.7 equiv), and hydrobromic acid (2.00 mL) and heated to reflux for 2 h. The reaction mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. Purification by column chromatography using 20% ethyl acetate in hexanes elution gave 2.07 g of the white solid, 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 g | Under ice cooling, water (20 mL), hydrobromic acid (content 48%, 20 mL) and bromoacetaldehyde diethyl acetal (45 mL) was added to, and stirred for 1 hour 30 minutes at room temperature. After stirring the reaction solution with ice-cold vigorously was added sodium hydrogen carbonate (31 g), the reaction solution was filtered. To the filtrate, ethanol (122 ml) and 2-amino-5-bromopyrimidine (21 g) was added and stirred for 35 min at 85 C. To the reaction solution was ice-cooled, water (244 mL) was added, was neutralized with sodium hydroxide solution of 4M, and stirred for 30 minutes. Collected by filtration resulting suspension, water (60 mL), followed by n- washed with hexane (60 mL), to give after drying the title compound (20 g) as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38%; 30% | With potassium carbonate; In dimethyl sulfoxide; at 70 - 80℃; for 15h; | General procedure: Halo acetal 2a or 2b, 0.25 mol, was added with stirring to a mixture of 0.25 mol of the corresponding CH acid and 28 g (0.2 mol) of calcined potassium carbonate in 100 mL of DMSO. The mixture was stirred for 15 h at 70? 80°C (in the reactions with 2a), or at 100?120°C (2b), cooled, and treated with water and diethyl ether (2 100 mL). The combined extracts were dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was distilled under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With caesium carbonate; In N,N-dimethyl-formamide; at 70℃;Inert atmosphere; | To a solution of 7-chloro-1 ,2-dihydro-1 ,8-naphthyridin-2-one (1.80 g, 10.0 mmol) and 2- bromo-1 , 1-diethoxyethane (4.92 g, 25.0 mmol) in DMF (25 mL) was added Cs2C03 (4.90 g, 15.0 mmol) and the mixture heated at 70C under N2 overnight. The mixture was diluted with H2O (200 mL), extracted with EtOAc (100 mL x 3) and the combined organic extracts were washed with H2O (200 mL x 2), brine (100 mL) and concentrated under reduced pressure. The residue was purified by chromatography (EtOAc/petroleum ether, 1 :5 to 1 :2, v/v) to afford a white solid of 7-chloro-1-(2,2-diethoxyethyl)-1 ,2-dihydro-1 ,8-naphthyridin-2- one 5a (1.80 g, 61 %). TLC: Rf = 0.45 (silica gel, petroleum ether/EtOAc = 2 : 1 , v/v). 1 H NMR (Method E) (CDC ): delta ppm 7.78 (d, J = 8.0 Hz, 1 H), 7.61 (d, J = 9.6 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 1 H), 6.72 (d, J = 9.6 Hz, 1 H), 5.10 (t, J = 5.6 Hz, 1 H), 4.67 (d, J = 5.6 Hz, 2H), 3.79 (m, 2H), 3.54 (m, 2H), 1.1 1 (t, J = 7.2 Hz, 6H). |
61% | With caesium carbonate; In N,N-dimethyl-formamide; at 70℃;Inert atmosphere; | To a solution of 7-chloro-1 ,2-dihydro-1 ,8-naphthyridin-2-one (1.80 g, 10.0 mmol) and bromoacetaldehyde diethyl acetal (4.92 g, 25.0 mmol) in DMF (25 ml_) was added CS2CO3 (4.90 g, 15.0 mmol) and the mixture heated at 70C under N2 overnight. The mixture was diluted with H2O (200 ml_), extracted with EtOAc (100 ml_ x 3) and the combined organic extracts were washed with H2O (200 ml_ x 2), brine (100 ml_) and concentrated under reduced pressure. The residue was purified by chromatography (EtOAc/petroleum ether, 1 :5 to 1 :2, v/v) to afford a white solid of 7-chloro-1-(2,2-diethoxyethyl)-1 ,2-dihydro-1 ,8- naphthyridin-2-one 5a (1.80 g, 61 %). TLC: Rf = 0.45 (silica gel, petroleum ether/EtOAc = 2 : 1 , v/v). 1 H NMR (Method E) (CDC ): delta ppm 7.78 (d, J = 8.0 Hz, 1 H), 7.61 (d, J = 9.6 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 1 H), 6.72 (d, J = 9.6 Hz, 1 H), 5.10 (t, J = 5.6 Hz, 1 H), 4.67 (d, J = 5.6 Hz, 2H), 3.79 (m, 2H), 3.54 (m, 2H), 1.1 1 (t, J = 7.2 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.6% | In a 250 mL single-necked flask, bromoacetaldehyde diethyl acetal (42.5 g, 215.7 mmol) was dissolved in 1 mol / L HCL(120 mL) and ethanol (20 mL), stirred at room temperature for 30 min, heated to reflux, stirred until the solution was clear, cooled to room temperature,Add NaHCO3 adjusted to near neutral,2-Amino-5-nitropyridine (15.0 g, 107.8 mmol) was added and reacted at room temperatureovernight. The reaction was completed, extracted with ethyl acetate (100mL × 3), the organic phase was collected and the solvent was evaporated to dryness under reduced pressure. The residue was passed through a silica gel column (PE:EA = 2: 1) to give 13.7 g of 6-nitroimidazo [1,2-a] pyridine yellow-brown crystals in a yield of 77.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.71 g | With toluene-4-sulfonic acid; In ethanol; at 80.0℃; | A mixture of 3-bromo-5-chloro-2-pyridinamine (5.0 g), bromoacetoaldehyde diethyl acetal (7.3 mL), p-toluenesulfonic acid monohydrate (498 mg) and ethanol (20 mL) was stirred at 80 C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a residue. The obtained residue was washed with ethyl acetate/IPE to give the title compound (4.71 g). (1141) 1H NMR (300 MHz, DMSO-d6) delta 7.68 (1H, d, J=1.2 Hz), 7.75 (1H, d, J=1.8 Hz), 8.06 (1H, d, J=1.2 Hz), 8.91 (1H, d, J=1.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.3% | To a 250 ml four-necked flask equipped with a stirring, thermometer, and reflux condenser was added 80 g of N, N-dimethylformamide.8.5 g (0.02 mol) of (S) -2- (1-but-2-ynylpyrrolidin-2-yl) -4- [4- (pyridin-2-yl) carbamoyl] prepared in Example 8 Phenyl-5-cyanoimidazole (VI),3.0 grams (0.022 moles) of potassium carbonate,4.9 g (0.025 moles) of 2-bromoacetaldehyde diethanol,Stir the reaction at 40 to 45 C for 7 hours, and then cool to 20 to 25 C.Add 2.7 g (0.05 mol) of ammonium chloride, 8.0 g (0.08 mol) of 17 wt% ammonia water, stir the reaction at 50 to 55 C for 6 hours, cool to 20 to 25 C, add the resulting reaction mixture to 200 g of ice water, and filter. The filter cake was washed twice with water, 20 g each time, and 20 g isopropanol once, and dried to obtain 8.5 g of acortinib with a yield of 91.3% and a liquid purity of 99.6%. |
Tags: 2032-35-1 synthesis path| 2032-35-1 SDS| 2032-35-1 COA| 2032-35-1 purity| 2032-35-1 application| 2032-35-1 NMR| 2032-35-1 COA| 2032-35-1 structure
A287729 [3400-55-3]
2-Bromopropionaldehyde diethyl acetal
Similarity: 0.80
A341251 [22094-18-4]
1,3-Dibromo-2,2-dimethoxypropane
Similarity: 0.67
A287729 [3400-55-3]
2-Bromopropionaldehyde diethyl acetal
Similarity: 0.80
A194345 [17739-45-6]
2-(2-Bromoethoxy)tetrahydro-2H-pyran
Similarity: 0.70
A194345 [17739-45-6]
2-(2-Bromoethoxy)tetrahydro-2H-pyran
Similarity: 0.70
A341251 [22094-18-4]
1,3-Dibromo-2,2-dimethoxypropane
Similarity: 0.67
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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 |
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