Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 5307-14-2 | MDL No. : | MFCD00007903 |
Formula : | C6H7N3O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HVHNMNGARPCGGD-UHFFFAOYSA-N |
M.W : | 153.14 | Pubchem ID : | 4338370 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 44.07 |
TPSA : | 97.86 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.86 cm/s |
Log Po/w (iLOGP) : | 0.76 |
Log Po/w (XLOGP3) : | 0.53 |
Log Po/w (WLOGP) : | 0.78 |
Log Po/w (MLOGP) : | -0.3 |
Log Po/w (SILICOS-IT) : | -1.73 |
Consensus Log Po/w : | 0.01 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.46 |
Solubility : | 5.3 mg/ml ; 0.0346 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.16 |
Solubility : | 1.07 mg/ml ; 0.00698 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.04 |
Solubility : | 13.8 mg/ml ; 0.0904 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 3.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.26 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280 | UN#: | N/A |
Hazard Statements: | H317 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
> 90% | In acetone; | 1 ,4-diamino-2-nitrobenzene (2-nitro- 1,4-phenylenediamine) was selectively acetylated according to the method of McFarlane et al., J. Chem. Soc. Perkin Trans., 691 (1988) incorporated herein by reference. The amine meta to the nitro group is readily acetylated using acetic anhydride in acetone (the amine ortho to theintro group is strongly deactivated). The yield of 1-Amino-2-nitro-4-acetamidobenzene (2- nitro-4-acetamido aniline) was> 90%. Characterization: ?H NMR (CD3OD) d [ppm]: 8.3 (m, 1 H, ArH), 7.5 (M, 1 H, ArH), 6.9 (M, 1 H, ArH), 2.1 (s, 3 H, acetyl CH3) in good agreement with McFarlane. JR (nujolINaCl) n [cm?]: 3470 (s, str, HOAc), 3340-3150 (m, mlstr, acetamide ArNH + ArNH2), 1661 (s, str, acetaniide CO), 1643 (s, str, H bondedacetamide CO), 1592 (s, mlw, aryl stretch), 1547 (s, str, ArNO2) & 1512 (s, mArNO2). Anal. (Dried at 80 C) Calcd for C8H9N30,: C, 49.23; H, 4.65; N, 21.53. Found: C, 49.36; H, 4.55; N, 21.31. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In water; | Methyl chloroformate (34 g) was added dropwise with stirring to a mixture of 2-nitro-p-phenylenediamine (50 g), sodium bicarbonate (44.5 g) and water (700 ml). The temperature was maintained at 5 C. during the addition by means of external cooling. After the addition was complete the mixture was allowed to warm to room temperature and the stirring was continued for two hours. The solid was filtered off and recrystallized from isopropanol to give 4-methoxycarbonylamino-2-nitroaniline (50 g), m.p. 171-172 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With triethylamine In ethanol for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphoric acid; sulfuric acid at -5℃; Diazotization.Behandlung der Diazoniumsalz-Loesung mit wss. KI-Loesung; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; for 0.666667h;Reflux;Product distribution / selectivity; | A solution of 2-nitrobenzene-1,4-diamine (2.00 g; 13.1 mmol), di-tert-butyl dicarbonate (3.14 g, 14.4 mmol), and DIPEA (2.6 mL; 14.9 mmol) in dioxane (40 mL) was heated at reflux for 40 min, then allowed to cool to room temperature. The mixture was concentrated under reduced pressure and taken up in EA (100 mL). The EA solution was washed with water and the aqueous phase extracted with EA. The combined organic layers were washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated under reduced pressure to give tert-butyl 3-amino-4-nitrophenylcarbamate in quantitative yield as a brown solid. To a stirred solution of tert-butyl 3-amino-4-nitrophenylcarbamate (2.74 g; 10.8 mmol) in anhydrous THF (50 mL) was added sodium hydride (0.868 g of a 60 wt % dispersion in oil, 21.7 mmol) in portions over 10 min. The mixture was stirred for a further 5 min at room temperature and then iodoethane (950 muL; 11.9 mmol) was added. The solution was stirred for 20 hr, water (1 mL) was added, and the solution concentrated under reduced pressure. The residue was partitioned between EA and water and the phases separated. The aqueous phase was extracted twice with EA and the combined organic phases washed with water, saturated aqueous sodium bicarbonate and brine. The organic solution was dried over magnesium sulfate and concentrated under reduced pressure to give a mixture of mono- and di-ethylated products (2.18 g). This was purified by silica gel column chromatography eluting with 1:4 EA/hexanes to give tert-butyl 4-amino-3-nitrophenyl(ethyl)carbamate (0.534 g) as an orange solid. A solution of tert-butyl 4-amino-3-nitrophenyl(ethyl)carbamate (0.514 g; 1.83 mmol) in 4M hydrogen chloride in dioxane (10 mL) was stirred at ambient temperature for 3 hr. The solvent was removed under reduced pressure and the residue dissolved in water. The pH was adjusted to 10 with 1M aqueous sodium hydroxide and the aqueous phase was extracted three times with EA. The combined organic extracts were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to give N1-ethyl-3-nitrobenzene-1,4-diamine (0.311 g) as a purple solid. N1-Ethyl-3-nitrobenzene-1,4-diamine (0.208 g; 1.38 mmol) was dissolved in acetonitrile (10 mL) and N,N-diethylglycine sodium salt (0.192 g; 1.25 mmol) and DEPBT (0.375 g; 1.25 mmol) were added, followed by triethylamine (577 muL; 4.14 mmol). The mixture was stirred at room temperature for 8 hr; and then further quantities of N,N-diethylglycine sodium salt (0.192 g; 1.25 mmol), DEPBT (0.375 g; 1.25 mmol), and triethylamine (577 muL; 4.14 mmol) were added and stirring continued for 63 hr. Solids were removed by filtration and the filtrate concentrated under reduced pressure. Water was added to the residue and the pH was adjusted to 10 with saturated aqueous sodium bicarbonate. This solution was extracted three times with EA, and the organic extracts combined, washed with water and brine, dried over magnesium sulfate, and concentrated under reduced pressure to give N-(4-amino-3-nitrophenyl)-2-(diethylamino)-N-ethylacetamide (0.303 g) as a brown oil. A solution of N-(4-amino-3-nitrophenyl)-2-(diethylamino)-N-ethylacetamide (0.092 g; 0.31 mmol) in ethanol (5 mL) was hydrogenated at atmospheric pressure with 10% palladium on carbon (11 mg) at room temperature for 22 hr. The mixture was filtered through diatomaceous earth, washing with ethanol, and the filtrate was concentrated under reduced pressure to give N-(3,4-diaminophenyl)-2-(diethylamino)-N-ethylacetamide in quantitative yield as a brown oil. |
80% | In tetrahydrofuran; for 2h;Heating / reflux; | To a refluxing solution OF 2-NITRO-1, 4-DIAMINOBENZENE (10.135 g, 66.18 mmol) in tetrahydrofuran (100 mL) Boc20 (DI-TERT-BUTYL dicarbonate, 32.6 g, 149 mmol) was added by portions during 2 hours. The obtained solution was poured into heptane (2 L), sonicated for 15 minutes, filtered and dried in vacu to furnish 13.40 g of the title compound as a red solid. Yield 80%. |
In tert-butyl alcohol; at 40℃; for 1h; | A solution OF 2-NITRO-BENZENE-1, 4-diamine (1-1,1. 01 g, 6.53 mol) in tert-butanol (20 mL) was treated with di-tert-butyl dicarbonate (1.42 g, 6.53 mol) and heated at 40C. After lh stirring at the same temperature, the reaction mixture was cooled to the ambient temperature and concentrated in vacuo. The resulting crude mixture was dissolved in ethyl acetate, treated with active carbon, and filtered though a pad of Celite (3 g). The filtrate solution was concentrated in vacuo to afford the desired product as a deep orange powder. The intermediate (1-2) was dissolved in methanol (20 mL) and mixed with palladium on carbon (10%, 50 mg). Hydrogen gas was bubbled into the reaction mixture at the ambient temperature for LH. Any insoluble material was removed by filtration and the filtrate solution was concentrated in vacuo. The resulting crude product was triturated with ethyl acetate (10 mL) and hexanes (2 mL) to give (4- Amino-3-nitro-phenyl) -carbamic acid tert-butyl ester (1-3) as a pale gray solid. The product was stored at-15 OC in a brown bottle ; 1H NMR (500 MHz, DMSO-d6) 8 8.82 (s, 1 H), 6.84 (s, 1 H), 6.56 (d, 1 H, J = 8.5 Hz), 6.49 (d, 1 H, J = 8.0 Hz), 5.71 (bs, 4 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With magnesium iodide etherate; In acetonitrile; at 80℃; for 12h; | General procedure: A Schlenk reaction tube was charged with primary aromatic amine (5.0 mmol), 2,5-dimethoxytetrahydrofuran (6.0 mmol), MgI2 etherate (10% mmol), and acetonitrile (10 mL). The reaction mixture was stirred at 80 C for several hours and then concentrated in vacuo. The residue was purified by flash column chromatography on a silica gel to give the desired product. |
In acetic acid; at 95℃; for 3h; | Compound PI was prepared from 2-NITRO-1, 4-phenylenediamine [CAS-No. 5307-14-2] (20 g, 131 mmol) and 2, 5-DIMETHOXYTETRAHYDROFURAN (18.3 mL, 135 mmol) in HOAC (37 ml) at 95C for 3 h according to the general procedure F. General procedure F : Preparation of 2-nitro-4-pyrrol-1-yl-phenylamines by condensa- tion OF 2-NITRO-1, 4-phenylenediamine with 2, 5-DIMETHOXYTETRA- HYDROFURAN [CF. J. HETEROCYCL. Chem. 25: 1003-1005 (1988) ] A mixture of the 2-nitro-1, 4-phenylenediamine (25 mmol) and 2,5-dimethoxytetra- hydrofuran (26-32.5 mmol) in HOAC (150 mL) was stirred at 60-120C until tlc indicated complete conversion of the phenylenediamine. After cooling to 23C, the mixture was poured into brine (500 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (300 mL) and dried over MGSO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with CYCLOHEXANE/ETOAC to give the title compound. | |
In acetic acid; | Example F1 2-Nitro-4-pyrrol-1-yl-phenylamine The title compound was prepared from <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> [CAS-No. 5307-14-2] (20 g, 131 mmol) and 2,5-dimethoxytetrahydrofuran (18.3 mL, 135 mmol) in HOAc (37 mL) at 95 C. for 3 h according to the general procedure F. Obtained as a red solid (13.5 g). MS (EI) 203 (M+). |
In acetic acid; | Example F1 2-Nitro-4-pyrrol-1-yl-phenylamine The title compound was prepared from <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (20 g, 131 mmol), 2,5-dimethoxytetrahydrofuran (18.3 mL, 135 mmol) in HOAc (37 mL) at 95 C. for 3 h according to the general procedure F. Obtained as a red solid (13.5 g). MS (EI) 203 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5,5-dimethyl-1,3-cyclohexadiene; water | 1 2-Amino-4-(4-fluorobenzylamino)-1-ethoxycarbonylaminobenzene. A solution of 15.3 g (100 mmol) 2-nitro-p-phenylenediamine and 13.6 g (110 mmol) 4-fluorobenzaldehyde in 400 ml xylene is heated under reflux in the presence of 0.5 g of an acid ion exchanger (for example Nafion) for 3 hours in a water separator. Insoluble constituents are filtered out hot and the mixture is allowed to stand overnight at room temperature. An orange-yellow solid crystallizes out. This solid is suction filtered, washed with a little toluene and dried in a vacuum. 22.0 g (85% of theory) 2-amino-5-(4-fluorobenzylideneamino)-nitrobenzene is obtained as orange-yellow crystals. M.p. 136°-139° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In ethanol; water; | Stage 2: 4-hydroxyethylamino-2-nitroanisole 618 g of the carbamate obtained according to Stage 1 are initially introduced into 2025 ml of water and 675 ml of ethanol, the mixture is heated to 60 C. and 766 g of a 50% strength potassium hydroxide solution are added in the course of 1.5 hours. The mixture is subsequently stirred at 60 C. for 2.5 hours, brought to pH 8 with glacial acetic acid and cooled. The product which has precipitated is filtered off, washed with water and dried at 50 C. in vacuo. Yield: 423.9 g of brown granules Purity: 93.2% Yield in % of theory, based on 4-amino-2-nitroaniline: 82.7% 4-Amino-2-nitroanisole content: 2500 ppm Melting point: 79 C. To obtain the product in a purity of >99% with a content of <600 ppm of 4-amino-2-nitroanisole, the product must be recrystallized several times from aqueous methanol: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With N,N-dimethyl-aniline; In acetonitrile; at 0 - 20℃; for 18h; | To a mixture of 2-nitro-benzene-1 ,4-diamine (10g, 65.30 mmol) and N1N- dimethylaniline (8.7 g, 71.83 mmol) in acetonitrile (310 ml) at 00C 4-isopropyl- benzenesulfonylchloride (13.85 g, 63.34 mmol) was added over a period of 1 h. The mixture was stirred at O0C for 1h and for 16 h at room temperature. After concentrating the mixture in vacuo the obtained oil was triturated with water. The precipitate was col¬ lected, washed with ethanol and dried in vacuo to give the product as a yellow powder (11.76 g, 54%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In water; | 1. 2,3'-dinitro-4'-aminodiphenylamine-4-carboxylic acid, sodium salt A mixture of (A) 5.03 g (0.025 mol) 4-chloro-3-nitrobenzoic acid and (B) 3.82 g (0.025 mol) 2-nitro-p-phenylenediamine, 2.54 g (0.027 mol) sodium carbonate and 10 ml water was heated for 7 hours to 120 C. in an autoclave. After cooling, the solution was concentrated to dryness. The residue was recrystallized from a mixture of ethanol and water. Yield: brown crystals, melting point above 350 C. (with decomposition) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2-Nitrobenzene-1,4-diamine (1.55 g, 10.1 mmol), N,N-diethylglycine sodium salt (1.61 g, 10.6 mmol) and DEPBT (3.02 g, 10.0 mmol) were suspended in acetonitrile (75 mL). Triethylamine (2.8 mL, 20.0 mmol) was added and the solution stirred overnight at room temperature. The brown precipitate which was formed was filtered and discarded. The filtrate was concentrated and the residue partitioned between EA and saturated aqueous sodium bicarbonate. The organic phase was washed with water and then with brine, dried over sodium sulfate, and the solvent removed under reduced pressure. The residue was dissolved in ethanol (50 mL) and hydrogenated at atmospheric pressure with 10% palladium on charcoal (1.0 g, 0.9 mmol) at room temperature overnight. Filtration and concentration under reduced pressure gave N-(3,4-diaminophenyl)-2-(diethylamino)acetamide as a light brown semi-solid, which solidified and turned blue on standing. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; | O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU, 4.96 g, 13.1 mmol) was added to a stirred solution of (R)-N-Boc-2-piperidinecarboxylic acid (3.00 g, 13.1 mmol) and DIPEA (9.0 mL, 51.2 mmol) in anhydrous DMF (50 mL). The mixture was stirred at room temperature for 5 min and then <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (3.00 g, 13.1 mmol) was added. The mixture was stirred for a further 18 hr, then the DMF was removed by evaporation. The residue was partitioned between water (200 mL) and EA (100 mL) and the phases separated. The aqueous phase was extracted with two further portions of EA (100 mL each) and the combined organic extracts washed with water, 1M sodium carbonate solution, water, and brine (100 mL each). The solution was dried over magnesium sulfate and concentrated to give (R)-tert-butyl 2-[(4-amino-3-nitrophenyl)aminocarbonyl]-piperidine-1-carboxylate as a brown solid (4.80 g).(R)-tert-Butyl 2-[(4-amino-3-nitrophenyl)aminocarbonyl]piperidine-1-carboxylate (4.80 g, 13.2 mmol) was suspended in dioxane (100 mL) and hydrogen chloride (75 mL of a 4M solution in dioxane) was added. The resulting dark colored solution was stirred at room temperature for 3.5 hr resulting in a yellow/brown suspension. The solid was collected by filtration and briefly dried under high vacuum. The solid was suspended in water, the pH was adjusted to pH 8 with 1M sodium carbonate solution and the resulting suspension stirred for 15 minutes. The solid was collected and dried under high vacuum to give (R)-N-(4-amino-3-nitrophenyl)piperidine-2-carboxamide hydrochloride salt as an orange solid (2.08 g). This was treated with 1M sodium carbonate solution (200 mL) and extracted with EA (3×). The combined EA extracts were washed with brine, dried over magnesium sulfate, and concentrated to give (R)-N-(4-amino-3-nitrophenyl)piperidine-2-carboxamide as an orange foam (1.77 g).(R)-N-(4-Amino-3-nitrophenyl)piperidine-2-carboxamide (2.09 g, 7.9 mmol) was dissolved in MeOH (50 mL), and paraformaldehyde (0.95 g) and sodium cyanoborohydride (0.50 g, 8.0 mmol) were added. The mixture was stirred at room temperature for 70 min, and water added dropwise. The solvent was evaporated and the residue partitioned between water and EA (150 mL each). The phases were separated and the aqueous phase extracted with EA (2×100 mL). The combined EA layers were washed with brine, dried over magnesium sulfate, and concentrated to give (R)-N-(4-amino-3-nitrophenyl)-1-methylpiperidine-2-carboxamide as an orange foam (2.17 g), which was used without purification.A solution of (R)-N-(4-amino-3-nitrophenyl)-1-methylpiperidine-2-carboxamide (2.17 g, 7.8 mmol) in ethanol (75 mL) was degassed under vacuum and then backfilled with argon. 10% Palladium on carbon (0.44 g) was added and the mixture again degassed under vacuum. Hydrogen was introduced by a balloon and the reaction stirred at room temperature for 23 hr. The mixture was degassed by bubbling argon through it, and was then filtered through a pad of diatomaceous earth. The filtrate was concentrated to give (R)-N-(3,4-diaminophenyl)-1-methylpiperidine-2-carboxamide as a purple solid (1.78 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triethylamine; 3-[(diethoxyphosphinyl)oxy]-1,2,3-benzotriazin-4(3H)-one; In acetonitrile; at 20℃; for 96h; | To a solution of 1H-imidazole-1-ylacetic acid (284 mg, 2.25 mmol) and 2-nitrobenzene-1,4-diamine (324 mg, 2.12 mmol) in acetonitrile (20 mL) was added 3-diethoxyphosphoryloxy-1,2,3-benzotriazin-4(3H)-one (DEPBT, 632 mg, 2.11 mmol) and triethylamine (600 muL, 4.4 mmol). The mixture was stirred for 4 d at room temperature. The red precipitate was collected by filtration and washed with acetonitrile to give N-(4-amino-3-nitrophenyl)-2-(1H-imidazol-1-yl)acetamide (430 mg, 88% yield), 98% pure. A solution of N-(4-amino-3-nitrophenyl)-2-(1H-imidazol-1-yl)acetamide (430 mg, 1.65 mmol) in ethanol (20 mL) was hydrogenated at atmospheric pressure with 10% palladium on carbon (100 mg, 0.09 mmol) at room temperature overnight. The mixture was filtered, giving a blue solution. Removal of the solvent under reduced pressure gave N-(3,4-diaminophenyl)-2-(1H-imidazol-1-yl)acetamide (413 mg) as a blue semi-solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In ethanol; for 16h;Reflux; | 2-Nitro-1,4-phenylene diamine (0.6g, 1mmol) was refluxed with pyrrole 2-carboxaldehyde (0.435g, 1mmol) in ethanol (10ml) for 16h. Reaction mixture was concentrated under vacuum and the residue was triturated with n-hexane. The residue was filtered and dried to yield pure (2) (73% yield) 1H NMR (delta ppm, 400MHz, DMSO-d6): 11.6 (1H, s), 8.3 (1H, s), 7.7 (1H, d), 7.4 (3H, m) 7.0 (1H, d), 6.9 (1H, d), 6.6 (1H, d), 6.1 (1H, d). 13C NMR (delta ppm, 100MHz, DMSO-d6): 148.6, 144.3, 140.0, 130.5, 130.1, 129.9, 123.6, 120.0, 116.0, 115.7, 109.6. IR (KBr, cm-1): 3480, 3429, 3395, 3254, 3119, 2892, 1772, 1634, 1596, 1557, 1503, 1451, 1369, 1339, 1249, 1095 LCMS: m/z 231.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: isopropyl alcohol / 75 °C 2: sodium hydroxide; sodium tetrahydroborate / 75 °C 3: sodium ethanolate / 1.5 h / 20 - 25 °C 4: hydrogen / 1 % platinum and 2% vanadium on carbon / ethanol / 3 h / 50 - 70 °C / 1500.15 Torr / Inert atmosphere; Industry scale | ||
Multi-step reaction with 4 steps 1.1: isopropyl alcohol / 3 h / 75 °C 1.2: 1 h 2.1: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 70 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine; dmap / 1,4-dioxane / 90 °C / Inert atmosphere 4.1: palladium on activated charcoal; hydrogen / methanol / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.3% | In methanol;Reflux; | Experiment-28: To the stirred solution of 2-nitro-p-phenylenediamine (50 g) in methanol (300 ml) is added 4-fluorobenzaldehyde (38.6 ml) slowly through addition funnel in 10-15 minutes at RT. Reaction mass is refluxed for 16-18 hrs. Then reaction mass is cooled to 0-5C and stirred for 30 minutes. Solid appeared is filtered, washed with chilled methanol and dried under vacuum at 40-45C to get 2-amino-5-(4- fluorobenzylideneamino)nitrobenzene (83.2 g) as product. Yield: 98.3%; HPLC Purity: 98.64% |
77.2% | With toluene-4-sulfonic acid; In toluene; for 3h;Reflux; | To a solution of <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> 5 (7.65 g, 0.05mol) and PTSA (0.25 g) in toluene (200 mL), was added 4-fluorobenzaldehyde(6.8 g, 55.0 mmol). The stirred reaction mixturewas heated to reflux under a water sepatator for 3 h. Themixture was filtered quickly through a Buechner funnel packedwith silica gel. The filtrate was stirred and allowed to cool toroom temperature over 6 h. The orange solid was filtered andwashed with petroleum ether (3×15 mL) to give an orangesolid (10.0 g, yield: 77.2%). The resulting solid was suspendedin a mixture of 1,4-dioxane (40 mL) and methanol (10 mL). Tothis suspension, was added three separate portions of NaBH4(1.2 g, 31.6 mmol) at 15-min intervals. The reaction was allowedto stir at room temperature for 2 h, and quenched withwater (200 mL). The resulting solid was collected by filtration,washed with water, and dried under vacuum to give compound6 (4.91 g, yield: 94%). 1H NMR (300 MHz, CDCl3): delta7.31 (t, J=8.1 Hz, 3H), 7.03 (t, J=8.7 Hz, 2H), 6.84 (dd, J=8.7, 2.7Hz, 1H), 6.69 (d, J=9.0 Hz, 1H), 5.74 (s, 2H), 4.25 (d, J=5.1 Hz,2H); LC-MS m/z (%): 284.1 (100) [M+Na]+. |
In isopropyl alcohol; at 75℃; | 4-Amino-2-nitroaniline (1.0 equiv.; 1.0 wt) was dissolved in I PA. The mixture was warmed to 75 C and 4-fluorobenzaldehyde (1.05 equiv.; 0.285 wt) was added. When formation of imine was complete, a solution of NaBH4 in 0.1 % NaOH was added. After complete reduction of the imine at 75 C, water was added to the hot mixture. The mixture was cooled and acetone (0.2 vol) was added. The mixture was cooled to 15 C and held for at least 30 minutes. Dark brown crystalline solid was collected, washed with water, and dried under vacuum at 50 - 55 C.Percent yield range observed: 79 - 85% |
In 5,5-dimethyl-1,3-cyclohexadiene; at 90℃; for 20h;Molecular sieve; | (4-Amino-3-nitrophenyl)[(4-fluorophenyl)methyl]amine (1-2). A solution of 2-nitro-/?- phenylenediamine (0.998 g, 6.19 mmol) and 3 A mol. sieves (3.00 g) in xylenes (30 mL) was heated to 90 C and treated with 4-fluorobenzaldehyde (0.690 mL, 6.27 mmol). The resulting solution was allowed to stir for 20 h, filtered through a short pad of S1O2, allowed to cool for 6 h, and the solid precipitate filtered off to give the crude imine (0.719 g), that was dissolved in 1,4- dioxane (4 mL) and MeOH (1 mL) and NaBH4 (0.157 g, 4.11 mmol) was added in 3 batches at 15 min intervals. The solution was stirred for 10 h, quenched with H20 (25 mL), and the solid filtered to give 1-2 (0.573 g, 2.19 mmol, 35%): Mp 113- 114 C; IR (ATR) 3517.98, 3497.88, 3395.77, 3372.60, 1578.67, 1503.24, 1406.73, 1329.96 cm 1 ; NMR (CDCI3, 400 MHz) delta 7.33 (app. dd, 2 H, / = 5.4, 2.2 Hz), 7.30 (d, 1 H, / = 2.8 Hz), 7.04 (app. t, 2 H, / = 8.6 Hz), 6.84 (dd, 1 H, / = 8.8, 2.8 Hz), 6.70 (d, 1 H, / = 8.8 Hz), 5.73 (br s, 2 H), 4.26 (d, 2 H, / = 4.0 Hz); 13C NMR (CDCb, 100 MHz) delta 162.3 (d, J = 245.0 Hz), 139.4, 138.3, 134.6 (d, J = 2.9 Hz), 132.6, 129.4 (d, J = 8.0 Hz), 125.4, 120.2, 115.7 (d, / = 22.0 Hz), 106.1, 48.4; HRMS (HESI) m/z calcd for C13H13N3O2F (M+H) 262.0986, found 262.0981. | |
In 5,5-dimethyl-1,3-cyclohexadiene; at 90℃; for 20h;Molecular sieve; Inert atmosphere; | A mixture of 2-nitro-pphenylenediamine (0.998 g, 6.19 mmol) and 3 A molecular sieves (3 g) in xylenes (30 mL) was heated to 90 oC and treated with 4-fluorobenzaldehyde (0.690 mL, 6.27 mmol). The reaction mixture was allowed to stir for 20 h, filtered through a short pad of SiO2, and allowed to cool for 6 h. A solid precipitate was filtered off and dried in vacuo to give crude imine (0.719 g), that was dissolved in 1,4-dioxane (4 mL) and MeOH (1 mL) and treated with NaBH4 (0.157 g, 4.11mmol) in 3 batches at 15 min intervals. The solution was stirred for 10 h, and quenched with H2O (25 mL). The solid precipitated was filtered and dried to give colorless (4-amino-3-nitrophenyl)[(4-fluorophenyl)methyl]amine (0.573 g, 2.19 mmol, 35%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In butan-1-ol; at 130℃; for 2h; | A solution of (R)-N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamide (165 mg, 0.53 mmol) prepared in Preparation 24 and <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (90 mg, 0.58 mmol) in n-butanol (2 ml) was stirred at 130C for 2 hours. The reaction mixture was cooled to room temperature and then dichloromethane (3 ml) was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then filtered. The resulting solid was dried in vacuo to give 120 mg of the product as a pale yellow solid. | |
120 mg | In butan-1-ol; at 130℃; for 2h; | A solution of (R)N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamide (165 mg, 0.53 mmol) prepared in Preparation 24 and <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (90 mg, 0.58 mmol) in n-butanol (2 ml) was stirred at 130 C. for 2 hours. The reaction mixture was cooled to room temperature and then dichloromethane (3 ml) was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then filtered. The resulting solid was dried in vacuo to give 120 mg of the product as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of (R)-tert-butyl [1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](ethyl)carbamate (85 mg, 0.22 mmol) prepared in Preparation 30 and <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (41 mg, 0.27 mmol) in n-butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate = 1/1 ? dichloromethane/methanol = 10/1) and then dissolved in methanol. Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 5 hours and then filtered to give 104 mg of the product as a pale red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In ethanol;Reflux; | In 100 ml round bottom flask, add 4 - bromo - 1, 8 - naphthalenedicarboxylic anhydride (1) 1 mmol, 2 - nitro - 1, 4 - phenylenediamine (2) 1 mmol, then adding ethanol 10 ml, heating reflux for 5 - 6 h after, cooling to room temperature, vacuum filtration, the filter cake washing with ethanol for 2 - 3 times, vacuum drying, a yellow solid 4 - bromo - N - (3 - nitro -4 - aminophenyl) naphthalimide (3). Yield: 91%. The product directly without purification in the next step |
In ethanol;Reflux; | 4-bromo-1,8-naphthalic anhydride (554 mg, 2 mmol) and 2-nitrobenzene-1,4- diamine (306 mg, 2 mmol) were dissolved in20 mL ethanol, refluxed for 5-6 h. After the solution gradually deepened from the pale yellow to dark brown, the whole reaction system was cooled down and gradually deposited with yellow solid. After vacuum filtration, the cake was washed with ice ethanol for 2-3 times. After drying, the compound 1(774 mg, yield: 91%) was obtained without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.6% | With sodium tetrahydroborate; In water; isopropyl alcohol; at 20℃; | Experiment-30: Charged 2-nitro-p-phenylenediamine (10 g) and 4- fluorobenzaldehyde (9.3 ml) in isopropyl alcohol (125 ml) and DM water (5.9 ml) mixture under stirring at RT. Then sodium borohydride (4.97 g) is added slowly in 2 hours in four equal lots at time interval of 30 minutes at RT and stirred at RT for 21-24 hrs. Then adjust the pH to 1.5-2.0 with 4N HC1 maintaining temperature 25-30C and stir for 30 minutes at RT. Then filtered the residue, washed with plenty of DM water and residue was then taken in DM water and stirred for 20-30 minutes. The solid appeared is filtered, washed with DM water and dried under vacuum at 40-45C to get 2-amino-5-(4-fluorobenzylamino) nitrobenzene (11.2 g) as product. Yield: 65.6%; HPLC Purity: 99.86% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
104 mg | A solution of (R)-tert-butyl [1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](ethyl)carbamate (85 mg, 0.22 mmol) prepared in Preparation 30 and <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> (41 mg, 0.27 mmol) in n-butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1?dichloromethane/methanol=10/1) and then dissolved in methanol. Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 5 hours and then filtered to give 104 mg of the product as a pale red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide;Inert atmosphere; | Compound A1a (3.4 g, 26 mmol, Combi Blocks) and B9a (Aldrich, 4.0 g, 26 mmol) and DIPEA (9.1 ml_, 52 mmol) are dissolved in DMF (60 ml.) and HATU (9.4 g, 25 mmol) is added. The reaction is stirred overnight and then is partitioned between EtOAc and saturated NaHC03. The organic layer is washed with water and then brine, dried over MgS04 and concentrated. The residue is purified by Combiflash to give B9b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; | 1-17 (4-Amino-3-nitrophenyl)[(3-pentafluorothiophenyl)methyl]amine (1-17). A solution of 2-nitro- p-phenylenediamine (0.756 g, 4.69 mmol) and PTSA (0.054 g, 0.28 mmol) in toluene (25 mL) was treated with 3-(pentafluorothio)benzaldehyde (1.10 g, 4.56 mmol) via syringe and the resulting solution was heated to reflux with a Dean-Stark trap for 5 h. The mixture was filtered through a Buchner funnel packed with a thin pad of S1O2 and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.571 g) as a bright orange-red solid, that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL) and NaBH4 (0.126 g, 3.30 mmol) was added in 3 portions at 15 min intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL), and extracted from brine with CH2CI2 (3 x 200 mL). The solvent was removed under reduced pressure and the resulting residue dried under high vacuum at 60 C for 12 h to give 1-17 (1.36 g, 3.69 mmol, 79%) as a dark red-purple powder: Mp 128-129 C (CH2CI2); IR (ATR) 3477.56, 3422.45, 3360.67, 3109.99, 1574.79, 1515.17, 1206.56; NMR (CDC , 400 MHz) delta 7.77 (s, 1 H), 7.68 (d, 1 H, 7 = 8.4 Hz), 7.53 (d, 1 H, 7.6 Hz), 7.47-7.43 (m, 1 H), 7.30 (d, 1 H, / = 2.8 Hz), 6.86 (dd, 1 H, / = 8.8, 2.8 Hz), 6.72 (d, 1 H, / = 8.8 Hz), 5.75 (br s, 2 H), 4.37 (s, 2 H), 3.89 (br s, 1 H); 13C NMR (CDCI3, 100 MHz) 154.4 (quint, / = 18.0 Hz), 140.3, 139.0, 138.5, 132.6, 130.7, 129.3, 125.4, 125.3-125.1 (overlapping quint.), 120.4, 106.4, 48.6; HRMS (HESI) m/z calcd for C13H13N3O2F5S (M+H) 370.0643, found 370.0641. | |
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; Inert atmosphere; | A solution of 2-nitro-pphenylenediamine (0.756 g, 4.69 mmol) and PTSA (0.054 g, 0.28 mmol) in toluene (25 mL) was treated with 3-(pentafluorothio)benzaldehyde (1.10 g, 4.56 mmol) via syringe and the resulting solution was heated to reflux with a Dean-Stark trap for 5 h. The mixture was filtered through a Buchner funnel packed with a thin pad of SiO2 and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.571 g) as a bright orange-red solid that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL), and NaBH4 (0.126 g, 3.30 mmol) was added in 3 portions at 15 min intervals. The solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL), and extracted from brine with CH2Cl2(3 x 200 mL). The solvent was removed under reduced pressure and the resulting residue dried under high vacuum at 60 oC for 12 h to give (4-amino-3-nitro)phenyl[(3-(pentafluorothio)phenyl)methyl]amine (1.36 g, 3.69 mmol, 79%) as a dark red-purple powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; | (4-Amino-3-nitrophenyl)[4-(trifluoromethyl)phenyl]methyl}amine (1-18). A solution of 2- nitro-/?-phenylenediamine (0.754 g, 4.68 mmol) and PTSA (0.054 g, 0.28 mmol) in toluene (25 mL) was treated via syringe with 4-(trifluoromethyl)benzaldehyde (0.640 mL, 4.69 mmol) and the resulting solution was heated at reflux with a Dean-Stark trap for 5 h. The mixture was filtered through a Buchner funnel packed with a thin pad of S1O2 and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.23 g) as a bright orange -red solid, that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL) and NaBH4 (0.120 g, 3.14 mmol) was added in 3 portions at 15 min intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL) and extracted from brine with CH2CI2 (3 x 200 mL). The solvent was removed under reduced pressure and the residue dried under high vacuum at 60 C to give 1-18 (1.141 g, 3.666 mmol, 78%) as a dark purple oil: IR (CH2CI2) 3483.58, 3370.03, 1573.93, 1521.07, 1324.97 cm 1 ; NMR (CDCb, 400 MHz) delta 7.60 (d, 2 H, / = 8.0 Hz), 7.48 (d, 2 H, / = 8.0 Hz), 7.28 (d, 1 H, / = 2.8 Hz), 6.85 (dd, 1 H, / = 8.8, 2.8 Hz), 6.71 (d, 1 Eta, / = 8.8 Hz), 5.47 (br s, 2 H), 4.37 (s, 2 H), 3.92 (br s, 1 H); 13C NMR (CDC13 100 MHz) delta 143.1, 139.1, 138.4, 132.6, 129.9 (q, / = 32.1 Hz), 127.8, 125.8 (q, / = 3.6 Hz), 125.3, 124.2 (q, / = 270.0 Hz), 120.3, 106.1, 48.5; HRMS (HESI) m/z calcd for C14H13N3O2F3 (M+H) 312.0954, found 312.0955. | |
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; Inert atmosphere; | A solution of 2-nitro-pphenylenediamine (0.754 g, 4.68 mmol) and PTSA (0.054 g, 0.28 mmol) in toluene (25 mL) was treated via syringe with 4-(trifluoromethyl)benzaldehyde (0.640 mL, 4.69 mmol). The mixture was heated at reflux with a Dean-Stark trap for 5 h, filtered through a Buchner funnel packed with a thin pad of SiO2, and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.23 g) as a bright orange-red solid that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL), and NaBH4 (0.120 g, 3.14 mmol) was added in 3 portions at 15 min intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL) and extracted from brine with CH2Cl2 (3 x 200mL). The solvent was removed under reduced pressure and the residue dried under high vacuum at 60 oC to give (4-amino-3-nitro)phenyl[4-(trifluoromethyl)phenyl]methyl}amine (1.141 g, 3.666 mmol, 78%) as a dark purple oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; | (4-Amino-3-nitrophenyl)[3-(trifluoromethyl)phenyl]methyl}amine (1-19). A solution of 2- nitro-/?-phenylenediamine (0.753 g, 4.67 mmol) and PTSA (0.050 g, 0.26 mmol) in toluene (25 mL) was treated via syringe with 3-(trifluoromethyl)benzaldehyde (0.620 mL, 4.64 mmol). The resulting solution was heated to reflux with a Dean-Stark trap for 5 h, filtered through a Buchner funnel packed with a thin pad of S1O2, and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.203 g) as bright orange solid, that was suspended in a mixture of 1,4-dioxane (3.7 mL) and MeOH (0.90 mL) and NaBH4 (0.117 g, 0.655 mmol) was added in 3 portions at 15 minute intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL), and extracted with CH2CI2 (3 x 100 mL). The combined organic extracts were washed with brine, dried (Na2S04), filtered, and the solvent evaporated under reduced pressure to give crude 1-19 (1.141 g). Purification by chromatography on S1O2 (70% CTLCk in hexanes) gave 1-19 (1.10 g, 3.35 mmol, 72%) as a dark purple powder: Mp 95-96 C (CH2CI2); IR (ATR) 3456.00, 3396.67, 3330.69, 1515.08, 1323.54 cm 1; NMR (CDCb, 400 MHz) delta 7.64 (s, 1 H), 7.55 (m, 2 H), 7.47 (m, 1 H), 7.29 (d, 1 H, / = 2.8 Hz), 6.86 (dd, 1 H, / = 8.8, 2.8 Hz), 6.71 (d, 1 H, / = 8.8 Hz), 5.74 (br s, 2 H), 4.36 (s, 2 H), 3.89 (br s, 1 H); 13C NMR (CDCI3, 100 MHz) delta 140.0, 139.16, 138.5, 132.6, 131.2 (q, 7 = 32 Hz), 131.0, 129.3, 125.4, 124.5 (q, / = 3.7 Hz), 124.4 (q, J = 3.8 Hz), 124.2 (q, J = 271 Hz), 120.3, 106.2, 48.6; HRMS (ESI) m/z calcd for C14H13N2O3F3 (M+H) 312.0954, found 312.0947. | |
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark; Inert atmosphere; | A solution of 2-nitro-pphenylenediamine (0.753 g, 4.67 mmol) and PTSA (0.050 g, 0.26 mmol) in toluene (25 mL) was treated via syringe with 3-(trifluoromethyl)benzaldehyde (0.620 mL, 4.64 mmol). The resulting solution was heated to reflux with a Dean-Stark trap for 5 h, filtered through a Buchner funnel packed with a thin pad of SiO2, and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.203 g) as bright orange solid, that was suspended in amixture of 1,4-dioxane (3.7 mL) and MeOH (0.90 mL) and NaBH4 (0.117 g, 0.655 mmol) was added in 3 portions at 15 minute intervals. The resulting solution was allowed to stir at rt for 3 h,quenched with H2O (25 mL), and extracted with CH2Cl2 (3 x 100 mL). The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and the solvent evaporated under reduced pressure to give crude product (1.141 g). Purification by chromatography on SiO2 (70% CH2Cl2 in hexanes) gave (4-amino-3-nitro)phenyl[3-(trifluoromethyl)phenyl]methyl}amine (1.10 g, 3.35 mmol, 72%) as a dark purple powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 24h;Reflux; Dean-Stark; | (4-Amino-3-nitrophenyl)(2,2,2-trifluoro-l-phenylethyl)amine (1-29). A solution of 2-nitro-/?- phenylenediamine (0.504 g, 3.13 mmol) and PTSA (0.034 g, 0.17 mmol) in toluene (15 mL) at rt was treated with 2,2,2-trifluoroacetophenone (0.544 g, 3.09 mmol) and was stirred at reflux for 24 h with a Dean-Stark trap. The reaction mixture was filtered through a pad of S1O2 and the solvent evaporated under reduced pressure to give the crude imine (0.170 g), which was suspended in 1,4- dioxane (4 mL) and MeOH (1 mL) and NaBH4 (0.125 g, 3.27 mmol) was added in 3 portions at 15 minute intervals. The resulting solution was allowed to stir at rt for 3 h. H2O (25 mL) was added and solution was extracted with CH2CI2 (3 x 20 mL). The organic phase was dried (Na2S04), filtered, and the solvent evaporated under reduced pressure. Further drying under high vacuum gave 1-29 (0.120 g, 0.386 mmol, 12%) as a dark red solid: Mp 126-127 C (CH2CI2); IR (ATR) 3436.04, 3387.95, 333.42, 1581.30, 1514.40, 1326.05, 1237.64; NMR (CDCI3, 400 MHz) delta 7.44-7.38 (m, 5 H), 7.33 (d, 1 H, / = 2.8 Hz), 6.89 (dd, 1 H, / = 9.2, 2.8 Hz), 6.69 (d, 1 H, / = 8.8 Hz), 5.75 (br s, 2 H), 4.84 (m, 1 H), 4.13 (d, 1 H, / = 7.6 Hz); 13C NMR (CDCI3, 100 MHz) delta 139.2, 136.6, 133.6, 132.3, 129.51, 129.2, 128.0, 126.0, 125.1 (q, / = 280.3 Hz), 120.3, 108.6, 61.4 (q, J = 30.0 Hz); HRMS (HESI) m/z calcd for C14H13N3O2F3 (M+H) 312.0954, found 312.0953. | |
With toluene-4-sulfonic acid; In toluene; for 24h;Reflux; Dean-Stark; Inert atmosphere; | A solution of 2-nitro-pphenylenediamine (0.504 g, 3.13 mmol) and PTSA (0.034 g, 0.17 mmol) in toluene (15 mL) at rt was treated with 2,2,2-trifluoroacetophenone (0.544 g, 3.09 mmol). The reaction mixture was stirred at reflux for 24 h with a Dean-Stark trap, and filtered through a pad of SiO2. The solvent was evaporated under reduced pressure to give the crude imine (0.170 g), which was suspended in 1,4-dioxane (4 mL) and MeOH (1 mL), and NaBH4 (0.125 g, 3.27 mmol) was added in 3 portions at 15-min intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL) and extracted with CH2Cl2 (3 x 20 mL). The organic phase was dried (Na2SO4), filtered, and the solvent was evaporated under reduced pressure. Further drying under high vacuum gave (4-amino-3-nitrophenyl)(2,2,2-trifluoro-1-phenylethyl)amine (0.120 g, 0.386 mmol, 12%) as a dark red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; for 18h;Reflux; Dean-Stark; | (4-Amino-3-nitrophenyl)[(4-fluorophenyl)methyl]amine-rf2 (1-34). A solution of 2-nitro-p- phenylenediamine (0.602 g, 3.73 mmol), PTSA (0.040 g, 0.21 mmol) and crude 1-33 (0.273 g) was heated to reflux with a Dean-Stark trap for 18 h. The solution was filtered through a thin pad of Si02 and the solvent evaporated under reduced pressure to give the crude imine (0.328 g) which was suspended in 1,4-dioxane (4 mL) and MeOH (1 mL) and NaBD4 (0.111 g, 2.60 mmol) was added in 3 portions at 15 minute intervals. The resulting solution was allowed to stir at rt for 3 h and was then quenched with H20 (25 mL) and filtered to give 1-34 (0.241 g, 0.915 mmol, 42% over 2 steps) as a dark purple powder: Mp 113-114 C (H20); IR (ATR) 3517.22, 3496.96, 3371.18, 1577.41, 1502.47, 1329.45 cm 1; NMR (CDCI3, 400 MHz) delta 7.34-7.27 (m, 3 H), 7.28 (d, 1 H, 7 = 2.4 Hz), 7.03 (t, 2 H, 7 = 8.6 Hz), 6.84 (dd, 1 H, 7 = 8.8, 2.4 Hz), 5.75 (br s, 2 H), 3.80 (br s, 1 H); 13C NMR (CDCb, 100 MHz) delta 162.3 (d, 7 = 244.0 Hz), 139.4, 138.3, 134.5 (d, 7 = 3.0 Hz), 132.5, 129.3 (d, 7 = 8.0 Hz), 125.5, 120.2, 115.7 (d, 7 = 21.3 Hz), 105.9, 47.7 (t, 7 = 20.6 Hz); HRMS (HESI) m/z calcd for Ci3Hii found 264.1110. | |
With toluene-4-sulfonic acid; In toluene; for 18h;Reflux; Dean-Stark; Inert atmosphere; | A solution of 2-nitro-pphenylenediamine (0.602 g, 3.73 mmol), PTSA (0.040 g, 0.21 mmol) and crude 4-fluoro[formyl-2H]benzaldehyde (0.273 g) was heated to reflux with a Dean-Stark trap for 18 h. The solution was filtered through a thin pad of SiO2 and the solvent was evaporated under reduced pressure to give a crude imine (0.328 g) which was suspended in 1,4-dioxane (4 mL) and MeOH (1 mL). After addition of NaBD4 (0.111 g, 2.60 mmol) in 3 portions at 15-min intervals, the reaction mixture was stirred at rt for 3 h, quenched with H2O (25 mL), and filtered to give (4-amino-3-nitrophenyl)[2H2(4-fluorophenyl)methyl]amine (0.241 g, 0.915 mmol, 42% over 2 steps) as a dark purple powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.241 g | With sodium borodeuteride; In 1,4-dioxane; methanol; at 20℃; for 3.75h; | (4-Amino-3-nitrophenyl)[(4-fluorophenyl)methyl]amine-rf2 (1-34). A solution of 2-nitro-p- phenylenediamine (0.602 g, 3.73 mmol), PTSA (0.040 g, 0.21 mmol) and crude 1-33 (0.273 g) was heated to reflux with a Dean-Stark trap for 18 h. The solution was filtered through a thin pad of Si02 and the solvent evaporated under reduced pressure to give the crude imine (0.328 g) which was suspended in 1,4-dioxane (4 mL) and MeOH (1 mL) and NaBD4 (0.111 g, 2.60 mmol) was added in 3 portions at 15 minute intervals. The resulting solution was allowed to stir at rt for 3 h and was then quenched with H20 (25 mL) and filtered to give 1-34 (0.241 g, 0.915 mmol, 42% over 2 steps) as a dark purple powder: Mp 113-114 C (H20); IR (ATR) 3517.22, 3496.96, 3371.18, 1577.41, 1502.47, 1329.45 cm 1; NMR (CDCI3, 400 MHz) delta 7.34-7.27 (m, 3 H), 7.28 (d, 1 H, 7 = 2.4 Hz), 7.03 (t, 2 H, 7 = 8.6 Hz), 6.84 (dd, 1 H, 7 = 8.8, 2.4 Hz), 5.75 (br s, 2 H), 3.80 (br s, 1 H); 13C NMR (CDCb, 100 MHz) delta 162.3 (d, 7 = 244.0 Hz), 139.4, 138.3, 134.5 (d, 7 = 3.0 Hz), 132.5, 129.3 (d, 7 = 8.0 Hz), 125.5, 120.2, 115.7 (d, 7 = 21.3 Hz), 105.9, 47.7 (t, 7 = 20.6 Hz); HRMS (HESI) m/z calcd for Ci3Hii found 264.1110. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 5h;Molecular sieve; | (4-Amino-3-nitrophenyl)(2-thienylmethyl)amine (1-37). A solution of thiophene-2- carboxaldehyde (0.125 mL, 1.34 mmol), 2-nitro-/?-phenylenediamine (0.210 g, 1.30 mmol), PTSA (0.035 g, 0.18 mmol), and 4 A mol. sieves (1.063 g) in CH2CI2 (3.1 mL) and MeOH (3.1 mL) was allowed to stir at rt for 5 h. The resulting solution was filtered through Celite and the solvent removed under reduced pressure to give a dark brown solid that was dissolved in CH2CI2 (20 mL), filtered through a thin pad of S1O2 eluting with the same solvent, and concentrated under reduced pressure to give crude imine (0.250 g) as a bright orange solid. The solid was suspended in 1,4- dioxane (1.5 mL) and MeOH (0.50 mL), NaBH4 (0.070 g, 1.83 mmol was added in 3 portions at 15 min intervals, and the resulting solution was allowed to stir at rt for 20 h. The reaction mixture was quenched by the addition of 1: 1 H20:CH2Cl2 (30 mL). The layers were separated and the aqueous layer was extracted with CH2CI2 (3 x 10 mL). The combined organic layers were washed with H2O (2 x 10 mL) and brine (2 x 10 mL), dried (Na2S04), filtered, and the solvent evaporated under reduced pressure. Further drying under high vacuum at 50 C gave 1-37 (0.230 g, 0.923 mmol, 71%) as a dark red solid: Mp 103-105 C (CH2CI2); IR (ATR) 3506.46, 3380.50, 3115.96, 1576.61, 1518.86, 1332.92 cm 1 ; NMR (CDCI3, 400 MHz) delta 7.37 (d, 1 H, 7 = 2.8 Hz), 7.23 (dd, 1 H, 7 = 4.8, 1.2 Hz), 7.03-7.02 (m, 1 H), 6.97 (dd, 1 H, 7 = 5.2, 3.6 Hz), 6.88 (dd, 1 H, 7 = 8.8, 2.8 Hz), 6.71 (d, 1 H, 7 = 8.8 Hz), 5.74 (br s, 2 H), 4.48 (s, 2 H), 3.83 (br s, 2 H); 13C NMR (CDCI3, 100 MHz) delta 142.2, 139.0, 138.5, 132.6, 127.1, 125.6, 125.6, 125.0, 120.2, 106.6, 44.2; HRMS (HESI) m/z calcd for C11H12N3O2S (M+H) 250.0645, found 250.0644. | |
With toluene-4-sulfonic acid; In methanol; dichloromethane; at 20℃; for 5h;Inert atmosphere; Molecular sieve; | A mixture of thiophene-2-carboxaldehyde (0.125 mL, 1.34 mmol), 2-nitro-p-phenylenediamine (0.210 g, 1.30 mmol), PTSA (0.035 g, 0.18 mmol), and 4 A mol. sieves (1.063 g) in CH2Cl2 (3.1 mL) and MeOH (3.1mL) was allowed to stir at rt for 5 h. The reaction mixture was filtered through Celite and the solvent removed under reduced pressure to give a dark brown solid that was dissolved in CH2Cl2 (20 mL), filtered through a thin pad of SiO2 (CH2Cl2), and concentrated under reduced pressure to give crude imine (0.250 g) as a bright orange solid. The solid was suspended in 1,4-dioxane (1.5 mL) and MeOH (0.50 mL) and treated with NaBH4 (0.070 g, 1.83 mmol) in 3 portions at 15 min intervals. The solution was allowed to stir at rt for 20 h and quenched by the addition of H2O/CH2Cl2 (1:1, 30 mL). The aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The combined organic layers were washed with H2O (2 x 10 mL) and brine (2 x 10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Further drying of the residue under high vacuum at 50 oC gave (4-amino-3-nitrophenyl)(2-thienylmethyl)amine (0.230 g, 0.923mmol, 71%) as a dark red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 18h;Molecular sieve; | (4-Amino-3-nitrophenyl)(l,3-thiazol-2-ylmethyl)amine (1-39). A solution of 2- thiazolecarboxaldehyde (0.115 mL, 1.27 mmol), 2-nitro-/?-phenylenediamine (0.209 g, 1.30 mmol), PTSA (0.025 g, 0.13 mmol), and 4 A mol. sieves (1.15 g) in CH2CI2 (3.1 mL) and MeOH (3.1 mL) was allowed to stir for 18 h at rt. The resulting solution was filtered through Celite and the solvent removed under reduced pressure to give a dark brown solid. This solid was suspended in CH2CI2 (20 mL), filtered through a thin pad of S1O2 eluting with the same solvent, and the solvent removed under reduced pressure to give crude imine (0.205 g) as a bright orange solid. The solid was suspended in 1,4-dioxane (2 mL) and MeOH (0.75 mL), NaBH4 (0.035 g, 0.92 mmol) was added in a single portion, and the resulting solution was allowed to stir at rt for 8 h. The reaction mixture was quenched by the addition of 1: 1 H20:CH2Ci2 (15 mL). The layers were separated and the aqueous layer was extracted with CH2CI2 (3 x 10 mL). The combined organic layers were washed with H2O (2 x 10 mL) and brine (2 x 10 mL), dried (Na2S04), filtered, and the solvent evaporated under reduced pressure. Further drying under high vacuum at 50 C overnight gave 1-39 (0.194 g, 0.775 mmol, 61%) as a dark red solid: Mp 161-162 C (CH2CI2); IR (ATR) 3469.82, 3380.19, 3349.79, 1584.11, 1518.80, 1384.29, 1330.62 cm 1 ; NMR (DMSO-de, 500 MHz) delta 7.74 (d, 1 H, J = 3.0 Hz), 7.58 (d, 1 H, / = 3.0 Hz), 7.04 (br s, 2 H), 7.02 (d, 1 H, / = 3.0 Hz), 6.99 (d, 1 H, / = 2.5 Hz), 6.90 (d, 1 H, / = 9.0 Hz), 6.39 (t, 1 H, / = 6.0 Hz), 4.54 (d, 2 H, / = 6.0 Hz); 13C NMR (DMSO-de, 125 MHz) delta 171.8, 142.4, 140.1, 138.2, 129.9, 126.5, 120.4, 119.9, 103.0, 45.6; HRMS (HESI) m/z calcd for C10H11N4O2S (M+H) 251.0597, found 251.0595. | |
With toluene-4-sulfonic acid; In methanol; dichloromethane; at 20℃; for 18h;Inert atmosphere; Molecular sieve; | A suspension of 2-thiazolecarboxaldehyde (0.115 mL, 1.27 mmol), 2-nitro-p-phenylenediamine (0.209 g, 1.30mmol), PTSA (0.025 g, 0.13 mmol) and 4 A molecular sieves (1.15 g) in CH2Cl2 (3.1 mL) and MeOH (3.1 mL) was stirred for 18 h at rt and filtered through Celite. The solvent was removed under reduced pressure to give a dark brown residue that was suspended in CH2Cl2 (20 mL), filtered through a thin pad of SiO2 (CH2Cl2), concentrated under reduced pressure to give crude imine (0.205 g) as a bright orange solid. The solid was suspended in 1,4-dioxane (2 mL) and MeOH (0.75 mL) and NaBH4 (0.035 g, 0.92 mmol) were added. The reaction mixture was stirred at rt for 8 h and quenched by the addition of H2O/CH2Cl2 (1:1, 15 mL). The aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The combined organic layers were washed with H2O (2 x 10mL) and brine (2 x 10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Further drying under high vacuum at 50 oC overnight gave (4-amino-3-nitrophenyl)(1,3-thiazol-2-ylmethyl)amine (0.194 g, 0.775 mmol, 61%) as a dark red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 21h;Reflux; Dean-Stark; | (4-Amino-3-nitrophenyl)[(4-pentafluorothiophenyl)methyl]amine (1-16). To a solution of 2- nitro-/?-phenylenediamine (0.751 g, 4.66 mmol) and PTSA (0.045 g, 0.24 mmol) in toluene (25 mL) was added 4-(pentafluorothio)-benzaldehyde (1.115 g, 4.707 mmol). The resulting solution was heated to reflux with a Dean-Stark trap for 21 h, the mixture was filtered through a Buchner funnel packed with a thin pad of S1O2, and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.10 g) as a bright orange-red solid, that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL) and NaBH4 (0.120 g, 3.14 mmol) was added in 3 portions at 15 min intervals. The resulting solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL) and the resulting solid collected by filtration. The crude compound was washed with H2O (500 mL) and dried under high vacuum to give 1 (1.09 g, 2.95 mmol, 63%) as a dark purple powder: Mp 129-130 C (H20); IR (ATR) 3522.90, 3397.94, 1576.91, 1531.83, 1327.68, 1216.31 cm 1; NMR (CDCI3, 400 MHz) delta 7.73 (d, 2 H, / = 8.4 Hz), 7.61 (d, 2 H, / = 8.4 Hz), 7.27 (d, 1 H, 2.8 Hz), 6.84 (dd, 1 H, / = 9.2, 2.8 Hz), 6.71 (d, 1 H, / = 8.8 Hz), 5.74 (br s, 2 H), 4.37 (s, 2 H), 3.92 (br s, 1 H); 13C NMR (CDCI3, 100 MHz) delta 153.2 (app. t, J = 17.5 Hz), 143.0, 138.9, 138.5, 132.6, 127.7, 126.5 (quint, J = 4.6 Hz), 125.3, 120.4, 106.2, 48.1; HRMS (HESI) m/z calcd for C13H13N3O2F5S (M+H) 370.0643, found 370.0645. | |
With toluene-4-sulfonic acid; In toluene; for 21h;Reflux; Dean-Stark; Inert atmosphere; | To a solution of 2-nitro-p-phenylenediamine (0.751 g, 4.66 mmol) and PTSA (0.045 g, 0.24 mmol) in toluene (25mL) was added 4-(pentafluorothio)benzaldehyde (1.115 g, 4.707 mmol). The resulting solution was heated to reflux with a Dean-Stark trap for 21 h, the mixture was filtered through a Buchner funnel packed with a thin pad of SiO2, and the filtrate was stirred and allowed to cool to rt. The solvent was removed under reduced pressure to give the crude imine (1.10 g) as a bright orange-red solid that was suspended in a mixture of 1,4-dioxane (5.2 mL) and MeOH (1.3 mL), and NaBH4 (0.120 g, 3.14 mmol) was added in 3 portions at 15 min intervals. The solution was allowed to stir at rt for 3 h, quenched with H2O (25 mL) and the resulting solid was collected by filtration. The crude product was washed with H2O (500 mL) and dried under high vacuum togive (4-amino-3-nitro)phenyl-[(4-(pentafluorothio)phenyl)methyl]amine (1.09 g, 2.95 mmol, 63%) as a dark purple powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With iodine; triethylamine; In dimethyl sulfoxide; at 120℃; for 24h; | 2-Fluoro-A^l-(4-fluorobenzyl)-4-nitrobenzene-l,3-diamine. To a stirred solution of 2,3- difluoro-6-nitroaniline (1.00 g, 5.57 mmol, 1.00 equiv) in dry DMSO (6 mL) were added 4- fluorobenzylamine (0.79 mL, 6.68 mmol, 1.20 equiv) followed by Et3N (0.93 mL, 6.68 mmol, 1.2 equiv) and 12 (cat. 5 mg). The reaction mixture was heated to 120 C for 24h. The reaction mixture was cooled to room temperature, diluted with water (30 mL) and extracted with EtOAc (3 x 30 mL). The separated organic layer was washed with brine, dried over Na2SC>4, filtered and concentrated under reduced pressure. To the residue was added small amount (5 mL) of Et20, sonicated, filtered, the filter cake was again washed with Et20 (3 x 3 mL) to afford a yellow solid (1.20 g). The filtrate was concentrated in vacuo, the residue was purified by flash column chromatography on silica gel (EtOAc/Hexanes/Et3N = 1:4:0.1 to 1 :3:0.1) to afford 0.2 g of the product as a yellow solid (1.40 g in total, 90%). 1H NMR (400 MHz, CDCb) delta 7.90 (dd, J = 9.6, 2.0 Hz, 1 H), 7.33 (dd, / = 8.4, 5.2 Hz, 2 H), 7.12-7.06 (m, 2 H), 6.12 (dd, / = 9.6, 8.0 Hz, 1 H), 6.07 (br, 2 H), 4.86 (br, 1 H), 4.47 (s, 2 H); 13C NMR (125 MHz, acetone-d6) delta 162.96 (d, J =243.2 Hz), 142.57 (d, J = 9.3 Hz), 138.54 (d, J = 228.2 Hz), 136.73 (d, J = 13.4 Hz), 136.24 (d, J = 3.4 Hz), 129.91 (d, J = 8.2 Hz), 125.38, 123.88 (d, J = 2.6 Hz), 116.14 (d, 7 = 21.6 Hz), 101.82 (d, / = 3.5 Hz), 46.24; 19F NMR (376 MHz, CDCB) delta -114.29 (s, IF), -161.05 (s, 1 F), IR (neat) 3504.6, 3387.1, 3329.3, 3070.2, 2950.9, 1625.5, 1601.3, 1578.9, 1549.1, 1506.2, 1483.8, 1267.6, 1239.6, 1174.4, 1086.8, 991.7, 848.2, 837.0, 820.2, 805.3, 751.2 cm-1; HRMS (ESI) m/z calcd for Ci3Hi2N302F2 [M+H]+ 280.0892, found 280.0890. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.17 g | With iodine; triethylamine; In dimethyl sulfoxide; at 120℃; for 4h; | 2-fluoro-4-nitro- -(3-(pentafluoro-lambda6-sulfan l)benz l)benzene-l,3-diamine. To a stirred suspension of 2,3-difluoro-6-nitroaniline (0.500 g, 2.78 mmol, 1.00 equiv) in dry DMSO (5 mL) were added 3-(pentafluorosulphanyl)benzylamine (0. 714 g, 3.06 mmol, 1.1 equiv) followed by Et3N (0.43 mL, 3.06 mmol, 1.1 equiv) and L (cat. 5 mg). The reaction mixture was heated to 120 C for 24h. The reaction mixture was cooled to room temperature, diluted with water (30 mL) and extracted with EtOAc (3 x 30 mL). The separated organic layer was washed with brine, dried over Na2S04, filtered and concentrated under reduced pressure. To the residue was added small amount of Et20 (2 mL), sonicated, filtered, the filter cake was again washed with Et20 (3 x 3 mL) to afford a yellow solid (0.51 g). The filtrate was concentrated in vacuo, the residue was purified by flash column chromatography on silica gel (Acetone/Hexanes = 1 : 10 to 1 :4 to 1:3) to afford 0.17 g of the product as a yellow solid (0.68 g in total, 63%). iotaEta NMR (400 Hz, CDCb) delta 7.85 (dd, / = 9.6, 1.6 Hz, 1 H), 7.72-7.68 (m, 2 H), 7.50-7.46 (m, 2 H), 6.07 (br,2 H), 6.02 (dd, J = 9.6, 8.0 Hz, 1 H), 4.50 (br, 1 H), 4.54 (d, J =1.5 Hz, 2 H); 13C NMR (100 MHz, acetone-de) delta 153.90 (t, / = 16.1 Hz), 141.31 (d, / = 9.4 Hz), 141.30, 137.63 (d, / = 228.7 Hz), 135.83 (d, / = 13.3 Hz), 135.68, 130.75, 129.47, 124.64 (t, / = 4.7 Hz), 124.43 (t, / = 4.7 Hz), 122.94 (d, / = 2.8 Hz), 100.68 (d, J = 3.0 Hz), 45.42; 19F NMR (376 MHz, CDCb) delta 84.01 (quint, J = 150.4 Hz, 1 F), 62.73 (d, / = 150.4 Hz, 4 F), -160.39 (s, 1 F); IR (neat) 3494.7, 3384.8, 1630.9, 1548.9, 1481.8, 1412.8, 1286.1, 1273.0, 1239.5, 1205.9, 1176.1, 1140.7, 1105.3, 1086.6, 890.9, 859.2, 820.1, 795.9, 775.4, 751.1, 687.8 cm-i; HRMS (ESI) m/z calcd for C13H12N3O2F2S [M+H]+ 388.0549, found 388.0549. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In 1,2-dichloro-ethane; at 20℃; for 8.25h; | 3.3 mmol of <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> and 20 ml of 1,2-dichloroethanein a 100 ml round bottom flask and stirred until completely <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> was dissolved, was added dropwise with stirring 3 mmol of 4-methyl-1,2,3-thiadiazole-5-formylphenyl isocyanate, dropwise over 15 minutes immediately thereafter precipitation,followed by stirring at room temperature for 8 hours. after completion of the reaction ,allowed to stand, the solid product was suction filtered, and the filtrate solvent wasremoved by rotary evaporation, ethyl acetate with volume ratio of 1:3: petroleum etherafter recrystallization in a refrigerator, the precipitated solid, the solid product wascombined with a volume ratio of 1 :3 of ethyl acetate: petroleum ether, washed and driedto obtain the product; mp: 230-232 C, 95% yield; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In 1,2-dichloro-ethane; at 20℃; for 8.25h; | 1.3 mmol of <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> and 20 ml of 1,2-dichloroethane in a 100 ml round bottom flask and stirred until completely <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> dissolved, stirring <strong>[5307-14-2]2-nitro-1,4-phenylenediamine</strong> was added dropwise to 3 millimoles of 4-methyl-1,2,3-thiadiazol-5-carboxylic acid isocyanate, dropwise over 15minutes immediately thereafter a precipitate was stirred at room temperature for 8hours, the reaction was complete, allowed to stand, the solid product was suctionfiltered, and the filtrate solvent was removed by rotary evaporation, ethyl acetate withvolume ratio of 1:3: petroleum ether and recrystallized into a refrigerator, theprecipitated solid, the solid product was combined with a volume of ethyl acetate 1:3:dried product was washed with petroleum ether; mp: 212-214 C, yield 87%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; | A solution of 2,4-diaminonitrobenzene (8 g; 52.2 mmol) and DIPEA (9.9 g; 76.6 mmol) in DCM (300 ml) was cooled to 0 C. and at this temperature trifluoromethanesulfonic anhydride (23 g; 81.5 mmol) was added dropwise within 90 mm. Then, it was stirred overnight, diluted with DCM, washed with saturated NaHCO3 solution, dried over Mg504 and evaporated in vacuo. The remainder was stirred with ether (3x400 ml). The combined supernatants were combined and N-(4-amino-3-nitrophenyl)trifluormethansulfona- mide was obtained afier chromatography purification on silica gel by elution with DCM; Yield: 12.2 g (82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper; In deuteromethanol; at 64 - 66℃; for 12h;Green chemistry; | In a 2 L four-necked flask equipped with a thermometer and a stirrer, 1000 ml of a 50% aqueous methanol solution was added.The stirring was started. When the temperature was stabilized to 64 C, 80 g of 2-nitro-p-phenylenediamine and 2 g of copper powder were added, and the temperature was maintained at 64-66 C, 48 g of ethylene oxide was introduced, and the reaction was carried out for 12 hours.Then, the temperature is lowered to 20 C, and the mixture is kept at 20 to 25 C for 5 hours, and the liquid is filtered after completion.After washing with water, a crude 3-nitro-4-hydroxyethylamino-N,N-dihydroxyethylaniline was obtained.The crude product was added to 10 volumes of 50% aqueous methanol solution, 1 time by weight of activated carbon, and heated to 70-72 C for decolorization, cooled to room temperature and filtered to obtain a pure product.The yield was 95% and the purity was 99.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68%Chromat. | With tetrahydrofuran; tert.-butylnitrite; dimethyl sulfoxide; at 30℃; for 1.5h;Green chemistry; | General procedure: A solution of amine 2 (5 mmol) in THF (3 mL) was added dropwise over 20 min to a solution of t-BuONO (7.5 mmol) and DMSO (0.5 mmol) in THF (7 mL) at 30 C. The mixture was stirred at 30 C until the starting materials 2 were consumed (monitored by TLC). The solvent was evaporated, and the yields of the low boiling point products were determined by GC; the high boiling point products were isolated by column chromatography on silica gel (hexane/ethyl acetate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Under the protection of argon, the starting material a (0.7094 g, 1 mmol),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC, 0.1917 g, 1 mmol),1-hydroxybenzotriazole (HOBT, 0.1351 g, 1 mmol),Triethylamine (0.5ml),Dimethylformamide (DMF, 2 ml) was dissolved in dichloromethane (10 mL).Ice bath for 30 min. Then, raw material b (0.1531 g, 1 mmol) was added thereto at room temperature overnight; after completion of the reaction, the reaction product was separated and purified by thin layer chromatography (dichloromethane:methanol = 15:1) to carry out the next reaction. . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 60℃; for 24h;Inert atmosphere; | The synthesis procedures of the other compounds are shown in Scheme S1. Cy7 (300mg, 1.037mmol) and 2-nitrobenzene-1,4-diamine (190mg, 1.244mmol) were dissolved in 5mL of anhydrous DMSO. Then, N,N-diisopropylethylamine (100muL) was added to the reaction mixture. The reaction was kept at 60C for 24h under nitrogen atmosphere. Next, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography on silica gel with a gradient of ethyl acetate; petroleum ether from 10:1 to 3:1 (v/v), and the black solid HCG was finally obtained (153.3mg, 32%). 1H NMR (400MHz, CDCl3) delta 8.91 (s, 1H), 8.02 (d, J=2.4Hz, 1H), 7.65 (d, J=12.7Hz, 1H), 7.41 (dd, J=8.8, 2.4Hz, 1H), 7.26-7.18 (m, 2H), 6.95-6.83 (m, 2H), 6.70 (d, J=7.8Hz, 1H), 6.13 (s, 2H), 5.47 (d, J=12.7Hz, 1H), 3.22 (s, 3H), 2.77 (t, J=6.1Hz, 2H), 2.67-2.60 (m, 2H), 1.91-1.83 (m, 2H), 1.69 (s, 6H). 13C NMR (100MHz, CDCl3) delta 160.8 (s), 158.5 (s), 144.8 (s), 142.8 (s), 142.8 (s), 141.9 (s), 139.1 (s), 132.2 (s), 130.8 (s), 128.9 (s), 127.8 (s), 124.5 (s), 121.7 (s), 120.3 (s), 119.3 (s), 117.1 (s), 106.3 (s), 92.9 (s), 46.1 (s), 29.3 (s), 28.3 (s), 26.7 (s), 26.6 (s), 21.4 (s). HRMS (ESI+): m/z found [M+H]+ 463.1889. molecular formula C26H28ClN4O2+, requires [M+H]+ 463.1895. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.2% | A mixture of 4-amino-2-nitroaniline (100.0 g, 0.653 mol), purified water (200 mL), concentrated hydrochloric acid (61.2 g, 0.588 mol), and cyanamide (35.7 g, 0.849 mol) was stirred at 80?90 for 3 hours. A solution of sodium carbonate (41.5 g, 0.392 mol) in purified water (500 mL) was slowly added to the reaction mixture at about 65 . The reaction mixture was stirred for 2 hours, cooled to about 10 , and then filtered. The resulting solid was dried in vacuo to obtain 112.5 g of the titled compound. (Yield: 76.2%). [91] 1H-NMR(600MHz, DMSO) delta 9.86(br, 1H), 7.80(s, 1H), 7.66(s, 2H), 7.56(s, 2H), 7.29(s, 1H), 7.15(s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine; In N,N-dimethyl-formamide; at 60 - 70℃; for 24h; | A mixture of 2,4-dinitro-1-chlorobenzene (6.53 mmol; 1.32 g;2.0 equiv.), 4-nitro-1,2-diaminobenzene (3.26 mmol; 0.5 g) andtriethylamine (6.86 mmol; 0.69 g; 0.95 mL; 2.1 es deger) in 20 mLDMF was heated to 6-e70 C for 10 h. Upon completion as shownby TLC, the mixturewas poured into 250 mLwater and the resultingsolidwas filtered and dried in air. Hexane/diethylether mixturewasadded to the oily residue at the bottom of the aqueous solution andthe obtained solid was combined. Orange solid; 1.34 g; 85% yield;m.p. >300 C; IR (ATR) w 3449, 3357, 3311, 3267, 3214, 3085, 1619,1583, 1521, 1300, 1124, 923, 833, 743 cm1; 1H NMR (400 MHz,DMSO-d6) delta 9.83 (s, broad 2H), 8.93 (m, 1H), 8.21 (m, 1H), 8.06-8.02(m, 2H), 6.87-6.82 (m, 4H), 6.66-6.62 (m, 1H); 13C NMR (100 MHz,DMSO-d6) delta 154.45, 152.55, 147.97, 136.79, 136.10, 130.27, 126.71,126.04, 123.40, 120.59, 117.04, 114.54, 109.99, 109.95; GC-MS (m/z):(C18H11N7O10, M.W:485.32), 484, 318. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With palladium on activated charcoal; hydrogen; potassium hydroxide; In para-xylene; at 100℃; under 760.051 Torr; for 20h;Schlenk technique; | Add 0.25 mmol of 4-amino-2-nitroaniline to the schlenk tube,0.5 mmol of o-diphenol, 0.015 mmol of palladium on carbon, 0.05 mmol of potassium hydroxide,1.5 ml toluene at 100 C,After stirring for 20 hours under H2 conditions (the pressure of hydrogen used is one atmosphere),Stop heating and stirring, cool to room temperature, and remove the solvent by rotary evaporation under reduced pressure.It is then separated and purified by column chromatography to obtain the target product.The volume ratio of the column chromatography eluent used was 4: 1 petroleum ether: ethyl acetate mixed solvent with a yield of 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With triethylamine; In dichloromethane; at 20℃; for 16h;Cooling with ice; | To an ice-cooled solution of 2-nitrobenzene-1 , 4-diamine 1 (5 g, 32.67 mmol) in dry DCM (100 mL) was added triethylamine (5.4 mL, 39.2 mmol) and benzenesulfonylchloride (5.7 g, 32.67 mmol). The reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with water (200 mL) to obtain a precipitate which was filtered. The solid was washed with DCM (100 mL) and then dried to get the title compound 2 which was used for next step without further purification. (Yield = 6 g, 62%). LCMS: 294 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; | 26.1 Step 1 : N-(4-Amino-3-nitro-phenyl)-2-(5-chloro-2-methoxy-phenyl)acetamide To a solution of 2-(5-chloro-2-methoxy-phenyl)acetic acid (2.88 g, 14.37 mmol) in DMF (65 ml_) was added DIPEA (2.74 ml_, 15.67 mmol) and HATU (5.96 g, 15.67 mmol) followed by 2-nitrobenzene-1 , 4-diamine (2 g, 13.06 mmol) and the mixture stirred at room temperature overnight. The resulting mixture was concentrated in vacuo and the residue dissolved in EtOAc and washed with water (30 ml_). A precipitate formed which was filtered from the biphasic mixture and the layers were separated. The organic portion was washed with brine, dried over Na2SC>4 and concentrated in vacuo. Purification of the crude material by chromatography on silica eluting with 10-70% EtOAc in heptanes afforded the title compound as a yellow powder. LC-MS (Method B): Rt 1.10 min; MS m/z 336.0/338.0 = [M+H]+ (100% 215 nm) 1 H NMR (500 MHz, Chloroform-d) d 7.93 (d, J = 1.8 Hz, 1 H), 7.71 (d, J = 9.0 Hz, 1 H), 7.46 (br. s, 1 H), 7.29 - 7.26 (m, 2H), 6.89 (d, J = 8.4 Hz, 1 H), 6.77 (d, J = 9.0 Hz, 1 H), 5.97 (s, 2H), 3.92 (s, 3H), 3.65 (s, 2H). |
Tags: 5307-14-2 synthesis path| 5307-14-2 SDS| 5307-14-2 COA| 5307-14-2 purity| 5307-14-2 application| 5307-14-2 NMR| 5307-14-2 COA| 5307-14-2 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :