There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
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. : | 2016-57-1 | MDL No. : | MFCD00008149 |
Formula : | C10H23N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MHZGKXUYDGKKIU-UHFFFAOYSA-N |
M.W : | 157.30 | Pubchem ID : | 8916 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 8 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 52.89 |
TPSA : | 26.02 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.28 cm/s |
Log Po/w (iLOGP) : | 2.97 |
Log Po/w (XLOGP3) : | -0.03 |
Log Po/w (WLOGP) : | 3.09 |
Log Po/w (MLOGP) : | 2.84 |
Log Po/w (SILICOS-IT) : | 2.78 |
Consensus Log Po/w : | 2.33 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.27 |
Solubility : | 84.8 mg/ml ; 0.539 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.07 |
Solubility : | 135.0 mg/ml ; 0.858 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.54 |
Solubility : | 0.0456 mg/ml ; 0.00029 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.43 |
Signal Word: | Danger | Class: | 8,6.1 |
Precautionary Statements: | P273-P280-P301+P310-P305+P351+P338-P310 | UN#: | 2922 |
Hazard Statements: | H301+H311-H314-H400 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With Co2Rh2/C In toluene at 180℃; for 6h; Autoclave; Inert atmosphere; | |
With nickel at 200℃; | ||
With hydrogen at 200℃; |
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 4 h / Cooling with ice 2: potassium carbonate / N,N-dimethyl-formamide / 4 h / 80 °C 3: potassium carbonate; 2-hydroxyethanethiol / N,N-dimethyl-formamide / 6 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In dichloromethane; water at 4 - 20℃; for 4.5h; | |
100% | With potassium carbonate In dichloromethane at 5 - 20℃; for 12.5h; | 1.1.4 Example 1.4: Synthesis of 2-bromo-N-decylacetamide (Compound 41. Briefly, decyl amine (10 g) was dissolved in 55 mL dichlorome thane. Potassium carbonate (13.2 g) was dissolved in 60 mL of distilled water followed by addition to the organic solution. The resulting two-phase solution was then cooled to 5 °C. A solution of bromoacetyl bromide (19.25 g) in dichloromethane (55 mL) was carefully added dropwise to the cooled solution while maintaining the temperature at 5 °C for about 30 min. Then the reaction mixture was stirred at room temperature for 12 hrs. The aqueous solution was separated and washed with dichloromethane (2 x 25 mL). The organic solution was washed with water (2 x 50 mL) and passed over the anhydrous Na2S04 and concentrated to yield a white solid quantitatively. Yield, 100%; 1H-NMR (CDC13, 400 MHz): δ/ppm 0.88-0.92 (t, terminal -CH3, 3H), 1.28-1.32 (d, - CH2(CH2)7CH3, 14H), 1.52-1.56 (m, -CH2(CH2)7CH3, 2H), 3.28-3.33 (q, -COOC H2-, 2H), 3.91 (s, -COCH2Br, 2H), 6.49 (br. s, amide -NHCO-, 1H). |
97% | With potassium carbonate In dichloromethane; water at 4 - 20℃; for 8.5h; |
With 1,2-dichloro-ethane at -10℃; | ||
With triethylamine In dichloromethane at -15℃; | ||
With potassium carbonate In dichloromethane; water at 4 - 20℃; for 12.5h; | ||
With potassium carbonate In dichloromethane; water at 4 - 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.4% | Stage #1: caffeic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 1-aminodecane In dichloromethane; N,N-dimethyl-formamide at 20℃; for 6h; | 5 2.3. General procedure for PyBOP-assisted amidation General procedure: Caffeic acid (2.78 mmol) was dissolved in diisopropylethylamine(0.48 mL) and dimethylformamide (4 mL). The reactionwas placed on ice and PyBOP (2.78 mmol) in dichloromethane(5 mL) was added. The mixture was stirred for 30 min. Then, theamine (2.78 mmol) was added, the reaction was allowed to reachroom temperature and stirred for an additional 6 h. The solventswere removed under reduced pressure and the residue was dissolvedin ethyl acetate (30 mL). The solution was washed withwater (3 10 mL), HCl 1M (3 10 mL) and brine (10 mL). Thecompounds were purified by column chromatography in dichloromethane/methanol (95:5 until 90:10) and recrystallized fromdichloromethane/n-hexane. The procedure was adapted fromGaspar et al. 2011.13 |
16% | With dicyclohexyl-carbodiimide In tetrahydrofuran at 50℃; for 7h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triethylamine at 20℃; for 5h; Cooling with ice; | General Procedure for Preparation of Piperic AcidAmides (4-24) General procedure: Oxalyl chloride (1.27 g, 10 mmol) was addedto a mixture of piperic acid (218 mg, 1.0 mmol) in CH2Cl2(5 mL) and the mixture was stirred at room temperature for3 h. The solvent and excess oxalyl chloride was then evaporatedunder reduced pressure. The crude acid chloride generatedwas dissolved in CH2Cl2 or N,N-dimethylformamide(DMF) (2 mL), and was added dropwise to a mixture of theappropriate amine or its hydrochloride salt (1.2 mmol) andEt3N (808 mg, 8 mmol) in CH2Cl2 or DMF (5 mL) under icecooling.The reaction mixture was stirred for 5 h at roomtemperature. Ice-water was added to the mixture, which wassubsequently extracted with CHCl3. The organic layer wasdried over Na2SO4 and the solvent was evaporated under reducedpressure. The residue was purified by silica gel columnchromatography (CHCl3 : MeOH : aq. NH3=100 : 1 : 0.1) to givethe corresponding piperic acid amides. |
85% | In tetrahydrofuran at 20℃; | |
56% | With triethylamine In tetrahydrofuran at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen In methanol at 20℃; for 29h; | |
82% | With palladium 10% on activated carbon; ammonium acetate; hydrogen In methanol at 20℃; for 29h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogen In methanol at 20℃; for 29h; | |
71% | With palladium 10% on activated carbon; ammonium acetate; hydrogen In methanol at 20℃; for 13h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.23% | With hydrogen In water at 150℃; for 6 - 8h; | 78-86 Examples 78-86; Preparation of 5-Methyl-1-Decyl-2-Pyrrolidone (DeMP) The feedstock used in examples 78 through 86 was 25% of the ammonium salt of levulinic acid, 25% decylamine, and 41% water, by weight. The temperature and pressure of the reactions were maintained at 150° C. and 6.9 MPa. Water was used as the solvent medium for the reactions. The results are set forth in the following table |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; ethyl acetate; | Example 2 N-(tert-Butoxycarbonyl)-(S)-(-)-2-azetidinecarboxylic Acid n-decyl Amide (285) N-(tert-Butoxycarbonyl)-(S)-(-)-2-azetidinecarboxylic acid (1) (90 mg; 0.447 mmol) is dissolved in methylene chloride (3 mL) at ambient temperature. n-Decylamine (72 mg; 0.470 mmol), N,N-diisopropylethylamine (116 mg; 0.895 mmol) and PyBOP (244 mg; 0.470 mmol) are added sequentially. The reaction is stirred for 4 days at room temperature, then concentrated under reduced pressure. The crude product is purified via silica gel chromatography using a gradient elution (10percent-->60percent ethyl acetate in hexanes) affording the desired product (285). ISMS: MH+341.4 Compounds 283, 284 and 286 are prepared in a similar manner using n-hexylamine, n-octylamine and n-dodecylamine, respectively, in place of n-decylamine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With triethylamine In tetrahydrofuran; thionyl chloride; water; N,N-dimethyl-formamide | 9 N,N'-Didecyl-5-nitro-1,3-benzenedicarboxamide EXAMPLE 9 N,N'-Didecyl-5-nitro-1,3-benzenedicarboxamide To 30 g (0.14 mol) of 5-nitroisophthalic acid suspended in 120 ml of thionyl chloride was added 2 ml of DMF and the solution was stirred at reflux for 3.5 hours. The excess thionyl chloride was removed at reduced pressure and the residue acid chloride was dissolved in 220 ml of anhydrous tetrahydrofuran. This solution was added dropwise to 64 ml (0.32 mol) of decyl amine and 44 ml (0.32 mol) of triethylamine in 350 mol of anhydrous tetrahydrofuran over 30 minutes with ice bath cooling. The reaction mixture was stirred at room temperature for 4 hours and then poured into 3 L of water. The resultant solid was removed by filtration and recrystallized from methanol to give 51.5 g (74% yield, mp 115°-116°) of N,N'-didecyl-5-nitro-1,3-benzenedicarboxamide. Anal. Calcd for C28 H47 N3 O4: C, 68.68; H, 9.67; N, 8.58. Found: C, 68.45; H, 9.56; N, 8.67. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogen;5% Pd(II)/C(eggshell); In methanol; at 50℃; under 3750.38 Torr; for 3.5h; | Example 4: Preparation of decylaminoethanal dimethylacetal III[000116] A mixture of glyoxal 1,1 -dimethylacetal (18.6 g, 107 mmol), decylamine (15.0 g, 95.4 mmol) and 5% Pd/C (0.15 g) in methanol (100 ml) was hydrogenated at 50C/5 bar for 3.5 h. The reaction mixture was then filtered through diatomaceous earth, and the apparatus and the filter cake were washed with MeOH (50 ml). The combined filtrate was evaporated under reduced pressure with two codistillations with toluene at 500C (90.6 mmol, Yield: 95%, purity: 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium hydroxide In chloroform; water at 0 - 20℃; for 2h; | 3 Decylamine (100, 2 g, 12.7 mmol) in 30 ml CHCl3 was mixed at O0C with 15 ml 2N NaOH. 2-mesitylenesulfonyl chloride (5, 2.76 g, 12.7 mmol) was added and the reaction mixture was stirred for 2 hrs at room temperature. The reaction was monitored by TLC (silica, hexane:EtOAc 9:1). The CHCl3 phase was separated, washed with NH4Cl solution (2X), dried, and evaporated to provide 3.58 g (83%) of N-decyl-mesitylene-2- sulfonamide (101). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: 3,5-dibromobenzoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: 1-aminodecane In dichloromethane at 20℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.1% | With potassium carbonate; In N,N-dimethyl acetamide; toluene; at 125℃; for 17h;Dean-Stark; | General procedure: The preparation of compound A7 is provided as a representative synthesis procedure of these compounds. (0012) Heptylamine (1.3186 g, 0.0114 mol) and 2,4-DFNB, (0.9262 g, 0.0058 mol) were weighed into separate vials. Potassium carbonate (3.03 g, 0.022 mol, 50% excess) was transferred to a 100 mL three-necked round-bottomed flask fitted with a magnetic stir bar, nitrogen inlet, thermometer, and a Dean-Stark trap fitted with a condenser. Each glass vial used for weighing starting materials was rinsed with DMAC (5 mL) and the washings were transferred to the reaction vessel to ensure full transfer of any residual reagents. Next, an additional 4 mL of DMAC was added to the reaction vessel, followed by 15 mL of toluene. An initial exotherm of 5 C was observed upon the dissolution of the starting materials, rendering the reaction mixture bright yellow in color. The reaction vessel was heated by an external temperature-controlled oil bath (with mild stirring) for 17 h at 125 C. At the completion of the reaction, the vessel was cooled, the reaction mixture was diluted with dichloromethane, and then filtered through celite to remove all salts. The filtrate was evaporated at reduced pressure to yield a crude product that was subsequently dissolved in dichloromethane and washed with water. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated at reduced pressure, and the resulting solid was further purified via recrystallization in absolute ethanol to yield yellow needles. Spectroscopic data for the secondary amines are supplied as Supplementary data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With C34H39N3O4Pd; sodium t-butanolate In 1,4-dioxane at 100℃; for 0.5h; Schlenk technique; Inert atmosphere; | 4.4 General procedure for the Buchwald-Hartwig amination reactions General procedure: In air, to a Schlenk tube that closed with a screw cap fitted with a septum and was equipped with a magnetic stir bar were added in turn complex 3 (0.01 mmol, 7 mg), and NaOBut (1.5 mmol, 144 mg). The tube was then caped with a rubber septum and evacuated and backfilled with argon. This sequence was repeated three times. Aryl chloride (1.0 mmol) and amine (1.1 mmol) was injected through the septum by syringe, followed by addition of dry 1,4-dioxane (10 mL). The mixture was then stirred at a pre-heated oil bath (100 °C) for the indicated time. The reaction mixture was cooled to room temperature and CH2Cl2 (25 mL) added. After filtration via a short pad of celite, the filtrate was condensed under vacuum and the residue was purified by flash chromatography on silica gel to provide the desired coupling products. Yields of isolated products were reported in Tables 1-3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With C34H39N3O4Pd; sodium t-butanolate In 1,4-dioxane at 100℃; for 0.75h; Schlenk technique; Inert atmosphere; | 4.4 General procedure for the Buchwald-Hartwig amination reactions General procedure: In air, to a Schlenk tube that closed with a screw cap fitted with a septum and was equipped with a magnetic stir bar were added in turn complex 3 (0.01 mmol, 7 mg), and NaOBut (1.5 mmol, 144 mg). The tube was then caped with a rubber septum and evacuated and backfilled with argon. This sequence was repeated three times. Aryl chloride (1.0 mmol) and amine (1.1 mmol) was injected through the septum by syringe, followed by addition of dry 1,4-dioxane (10 mL). The mixture was then stirred at a pre-heated oil bath (100 °C) for the indicated time. The reaction mixture was cooled to room temperature and CH2Cl2 (25 mL) added. After filtration via a short pad of celite, the filtrate was condensed under vacuum and the residue was purified by flash chromatography on silica gel to provide the desired coupling products. Yields of isolated products were reported in Tables 1-3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 2.7 - 10℃; for 1.5h;Inert atmosphere; | 4-{5-[Bis-(2-chloro-ethyl)-amino]-l-methyl-lH-benzoimidazol-2-yl}-N-decyl-butyramide (<strong>[3543-75-7]bendamustine</strong> do amide): A 250 mL three neck round bottom flask equipped with a stir bar, thermocouple, cooling bath, 60 mL pressure equalizing dropping funnel and nitrogen in/outlet was charged with 10.0 g (25.3 mmol) of <strong>[3543-75-7]<strong>[3543-75-7]bendamustine</strong> hydrochloride</strong>, 10.6 g (27.8 mmol) of HATU and 100 mL of Nu,Nu-dimethylfomramide (DMF). To this stirred yellow solution was added 4.41 mL (3.27 g, 25.3 mmol) of Nu,Nu-diisopropylethyelamine (DIPEA). An exotherm to 27.1C was noted and the solution became a darker yellow. The reaction was cooled to 6.6C where a solution of 6.2 mL (4.59 g, 35.5 mmol) of DIPEA, 5.11 mL (4.1 g, 25.6 mmol) of decyl amine in 20 mL of DMF was added drop-wise over 13 min at 2.7-7.6C. Once addition was complete the reaction was allowed to stir at <10C for 1.5 hours at which time an in process analysis indicated the reaction was complete. The batch was quenched onto 200 mL of DI water and extracted with ethyl acetate (2 X 175 mL). The organic phases were combined, washed with 10% sodium hydrogen phosphate (I X 200 mL), 8% aqueous sodium bicarbonate (I X 200 mL) and brine (I X 200 mL) before concentrating to dryness in vacuo to give a sticky white solid. This solid was triturated with heptanes (75 mL) and became a flowable solid which was isolated by vacuum filtration. The wetcake was dried in a vacuum oven at 25C overnight to yield 13.33 g (25.3 mmol, 100%) of the desired product as a white solid with an HPLC purity of 98.0 lA^o.1 NMR (400 MHz, DMSO-d6) delta 7.72 (s, b, 1H), 7.33 (d, J= 8.76 Hz, 1H), 6.91 (d, J = 2.28 Hz, 1H), 6.80 (dd, J= 2.36, 8.8 Hz), 3.7 (s, 8H), 3.66 (s, 3H), 3.01 (q, J= 6.8, 12.68, 2H), 2.79 (t, J= 7.44 Hz, 2H), 2.18 (t, J= 7.36 Hz, 2H), 1.95 (m, 2H), 1.36 (m, 2H), 1.22 (s, b, 14), 0.84 (t, J= 6.68 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With palladium 10% on activated carbon; hydrogen In methanol at 100℃; Flow reactor; | 4.2 Typical procedure for the palladium-catalyzed hydrogenation under the flow conditions (Tables 2 and 3) General procedure: A solution of the substrates possessing reducible functional groups (1mmol) within the molecule in MeOH (20mL) was flowed at 1mL/min into the catalyst-packed cartridge (10% Pd/C, 10% Pd/HP20, 0.5% Pd/MS3A, or 0.3% Pd/BN; 30mm long-cartridge, ca. 0.3mL volume) under 1, 50, or 80bar hydrogen gas at 25, 50, 75, or 100°C using H-Cube (ThalesNano Nanotechnology Inc.). Catalyst cartridges were filled with 10% Pd/C (99.4mg), 10% Pd/HP20 (101.4mg), 0.5% Pd/MS3A (99.6mg), and 0.3% Pd/BN (99.7mg). The reaction mixture was passed through the catalyst cartridge once and MeOH (the carrier solvent) was concentrated in vacuo to give an analytically pure product. The obtained product was identified by 1H NMR measurement. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In isopropyl alcohol; for 6h;Reflux; | A mixture of 1-decylamine (1.2 mL, 6.0 mmol), <strong>[16499-62-0]4-chloro-7-fluoroquinazoline</strong> (1.1 g, 6.0 mmol), and TEA (1.3 mL, 9.3 mmol) in 10 mL of IPA was heated at reflux for 6 hr. Then, the volatile components were evaporated, and the residue was partitioned between DCM (400, 300 mL) and 5% Na2C03 (400 mL). The organic phases were dried over anhydrous Na2S04, filtered through a pad of silica gel, washing with 10% MeOH/DCM, and concentrated. The product was crystallized from EA/Hex. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.04% | With papain adsorbed onto polyamide; In water; acetonitrile; at 37℃; for 72.0h;Inert atmosphere; Enzymatic reaction; | General procedure: Bz-Arg-OEt (0.2 mmol, 68.4 mg) and decylamine (0.3 mmol, 47.2 mg) or dodecylamine (0.3 mmol, 55.7 mg) were dissolved in anhydrous acetonitrile (10 ml) containing 0.25 % v/v water. Papain adsorbed onto polyamide (1 g) was added as biocatalyst. Individual reactions were performed under nitrogen atmosphere in Erlenmeyer flasks (100 ml) placed on an orbital shaker (250 rpm) at 37 C for 72 h. After incubation, the biocatalyst was removed by filtration and washed with acetonitrile (3 × 10 ml) and diethyl ether (3 × 10 ml), to eliminate the excess of fatty amine. Finally, reaction products were extracted from the biocatalyst surface using MeOH/H2O 4:1 (3 × 10 ml) and filtered through a nylon membrane filter (0.22 mum, Osmonics). Purification of each surfactant was achieved in an Aekta Purifier 10 (GE Healthcare) by cation exchange chromatography as follows: aliquots of the filtrate (1 ml) were loaded onto a SP Sepharose Fast Flow column (10 ml bed volume, GE Healthcare) preequilibrated with boric acid-sodium borate buffer 0.01 M pH 8.5/ethanol 1:1 (solvent A). Unbound material was eluted after washing the column with 2 bed volumes (BV) of the same solvent. Elution of each condensation product was accomplished by a step of 31 % of solvent B, consisting in boric acid-sodium borate 0.01 M pH 8.5 buffer/ethanol (1:1) with 1 M NaCl (2 BV). The column was washed with 100 % of solvent B (2 BV) and reequilibrated to the starting conditions. Flow rate was kept at 1 ml/min throughout the whole process. Eluted peaks were detected at 215 and 254 nm. Collected fractions containing the purified products were pooled and the solvent was evaporated. The resulting solid was desalted by precipitation with absolute ethanol and centrifugation. Supernatant was evaporated under vacuum. The purity of the products obtained was analysed by HPLC under the above conditions. Identities of both compounds were confirmed by 1H-NMR and 13C-NMR, using bidimensional techniques (HSQC and COSY, see Supplementary Material), as well as ESI MS. Theoretical exact masses were obtained using the ChemCalc online service (Patiny and Borel 2013) and compared with the experimental values obtained by ESI MS. Bz-Arg-NHC10, ESI (+)-TOF-MS [M + 1] calculated for C23H40N5O2: 418.31820; found: 418.31889. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: To a suspension of compound 8 (2 mmol) in THF (40 mL) was stirred at room temperature during addition of N,N'-carbonyldiimidazole (CDI, 3 mmol). The mixture was stirred for 2 h and treated with dropwise addition of various amines, alcohols or thiols (2.1 mmol) in anhydrous THF (10 mL). Then, the mixture was refluxed for more 6 h. The resulting reaction mixture was cooled to room temperature and distilled under reduced pressure. Water (50 mL) was added to remove excess CDI. The aqueous layer was extracted with methylene chloride (3 x 30 mL). The combined organic extract was washed with water (30 mL) and brine (30 mL), respectively, and then dried with anhydrous Na2SO4. The solvent was removed in vacuo, and the residue was purified by flash column chromatography (SiO2) using hexane/ethylacetate (8: 2) as eluent to afford compounds 9a-g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triethylamine; In dichloromethane; at 20℃; for 18h;Inert atmosphere; Darkness; | To a solution of n-decylamine (10 μL, 0.05 mmol) in CH2Cl2 (5 mL) were added Et3N (16 μL, 0.11 mmol) and <strong>[1426827-79-3]BCN-NHS</strong> (15 mg, 0.05 mmol), and the mixture was stirred at room temperature under an inert atmosphere of N2 in the dark for 18 h. The reaction was then quenched with H2O (10 mL). The product was extracted with CH2Cl2 (10 mL*3) and the combined organic extract was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel using n-hexane as the eluent. The solvent was removed under reduced pressure and the product was subsequently isolated as yellowish oil. Yield: 16 mg (87%). 1H NMR (400 MHz, CDCl3, 298 K, TMS): δ 4.67 (s, 1H), 4.16 (d, J=8.0 Hz, 2H), 3.18 (d, J=6.4 Hz, 2H), 2.34-2.21 (m, 6H), 1.68-1.59 (m, 2H), 1.52-1.45 (m, 1H), 1.44-1.37 (m, 16H), 0.99-0.94 (m, 2H), 0.89 (t, J=6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3, 298 K, TMS): δ 156.7, 98.8, 62.6, 41.1, 31.9, 30.0, 29.5, 29.3, 29.1, 26.8, 22.7, 21.4, 20.1, 17.8, 14.1. Positive-ion ESI-MS ion cluster at m/z 334 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: NH-pyrazole; bis(trichloromethyl) carbonate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: 1-aminodecane In dichloromethane at 20℃; Inert atmosphere; | Synthesis of N-decylpyrazole-1-carboxamide (34) Triphosgene (0.21 g, 0.73 mmol) in dry DCM (2.0 mL) was added at 0 °C to a solution of pyrazole 14b (0.05 g, 0.73 mmol) and DIPEA (0.51 mL, 2.92 mmol) in dry DCM (3.2 mL). After 1h, a solution of dodecylamine (0.25 mL, 1.1 mmol) and DIPEA (0.19 mL, 1.09 mmol) in dry DCM (1.5 mL) was added at rt and the reaction was stirred overnight. The reaction mixture was diluted with DCM and quenched with sat. aq. NH4Cl. The two phases were separated and the aqueous layer was extracted with DCM (3 × 10 mL). The combined organic phases were dried over Na2SO4 and the solvent removed under reduced pressure. The crude was purified by silica gel column chromatography (cyclohexane/EtOAc 95:5) to afford 34 (0.15 g, 84%) as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h; Inert atmosphere; | 2.5. Synthesis of Fmoc-Glu(NHC10H21)-NHC8H17 (4a) General procedure: To a dry solution of the corresponding glutamic acid derivative in CH2Cl2 (0.1 M) are subsequently added HOBT (1.0 eq.) and EDC·HCl (1.2 eq.). Next, the appropriate amine (1.2 eq.) is added to the reaction mixture and stirred at RT until TLC analysis revealed complete consumption of the starting material (usually 2 h). The reaction mixture is diluted with CH2Cl2 and subsequently washed with 1 M aq. HCl (3×), sat. aq. NaHCO3 (2×),1:1 H2O/brine (v/v), dried (MgSO4, filtered and concentrated.The crude material is subjected to FCC purifications,unless stated otherwise. |
84% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h; | 2-3 Preparation of Fmoc-Glu-(NHC10H21)-NHC8H17(4): Example 2-3 General procedure: FmocGlu(OH) NHC8H17(3, 0.72 g, 1.50 mmol) and decyl amine (0.35 , 1.80 mmol) was carried out using the method ofExample 13.Next, a cleaning and the removal of extracting volatile components, and then the produced compound wasdissolved in MeOH. Separated by filtration of the resultant colorless gel therefrom, washed with cold MeOH to give colorlesssolid in the form of the title compound in a yield of 84%. The solution to the glutamate derivative were dissolved in CH2Cl2 (0.1M) was added HOBT (1.0 equiv.) And EDC · HCl (1.2equiv.).Next, an appropriate amount of the amine (1.2 eq. ) Was added to the reaction mixture, stirred at room temperature until thestarting material is completely consumed through TLC analysis (usually 2 hours).The reaction mixture was diluted with CH2Cl2 and 1M HCl (3x), saturated NaHCO3 (2x) and H2O / function (1:1, v / v) for usesequentially, dried was brought, filtered and concentrated .Unless otherwise noted, the resulting material was purified via FCC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In ethanol at 60℃; for 72h; | 1 Eggplant type glass flask Kanto Chemical Co., Ltd. dibromohexane 1.0mL (6.5mmol), Kanto Chemical Co., Ltd. triethylamine 2.0 (14mmol), Tokyo Chemical Industry Co., Ltd. decylamine 2.9mL (14mmol ), Showa chemical Co., Ltd. ethanol 40mL addition, 72 hours at 60°C, stirring was carried out. After distilling off the solvent, washed with Kanto Chemical Co. diethyl ether, by performing vacuum drying N1, N6-didecyl-1,6-diamine 2.7g of (0.9 mmol) obtained (99% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With zinc(II) chloride In neat (no solvent) Reflux; | 4.1.2. General synthetic solvent free procedure for the preparationof Schiff bases (method B) General procedure: A mixture of (1R)-(+)-camphor (1.0 equiv.), the appropriate amine (2.0 equiv.), and anhydrous ZnCl2 (0.1% mol on camphor)wasreflux for 5e12 h. Diethyl ether was added to the reaction mixture,after completion of the reaction. The organic layerwaswashed withbrine, dried (Na2SO4) and evaporated. The crude product was purifiedby vacuum distillation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 1-aminodecane With trimethylaluminum In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: N-acetyl-β-methoxy-D-alanine ethyl ester In dichloromethane for 3h; Inert atmosphere; | (R)-2-Acetamido-N-benzyl-3-methoxypropanamide [(R)-Lacosamide] (1) General procedure: To a stirred solution of benzylamine (0.86 mL, 7.92 mmol) in CH2Cl2 (5 mL) was added Me3Al (2.0 M in toluene, 3.96 mL, 7.92 mmol) at r.t. and the solution was stirred for 10 min. The resulting solution was transferred to a solution of compound 4a (500 mg, 2.64 mmol) in CH2Cl2 (5 mL) under N2 and stirred for another 3.0 h. The reaction was quenched with 0.1 N HCl (20 mL) and the mixture was extracted with CH2Cl2 (2 × 25 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to give crude 1, which was recrystallized from EtOAc to give pure lacosamide (1). |
56% | Stage #1: 1-aminodecane With trimethylaluminum In dichloromethane for 0.5h; Stage #2: N-acetyl-β-methoxy-D-alanine ethyl ester In dichloromethane for 3h; | 13 Decylamine0.528 mL and trimethyl aluminum 0.253 mL was added to dichloromethane,Stir for 30 min.Then, a solution prepared by dissolving 100 mg of the compound of formula (4a) in 2 mL of dichloromethane was slowly added.After confirming that the starting material disappeared after 3 hours,0.1 N hydrochloric acid was added little by little at 0 and stirred.Then, dichloromethane was added to the reaction mixture,0.1N hydrochloric acid was added and the layers were separated.The water of the obtained organic layer was removed using magnesium sulfate anhydride and filtered.The organic layer was dried under reduced pressure to remove the solvent,Ethyl acetate was used to recrystallize the compound to obtain a compound of formula 1g (56%, 89 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; Inert atmosphere; Cooling with ice; | C2-Alkylamine Analogues 19a-c; General Reductive Amination Procedure General procedure: To a stirred, ice-cooled solution of the bicyclic lactol 3 (1 equiv) in anhydrous THF (10% solution w/v) was added NaBH(OAc)3 (1.2 equiv) followed by the respective alkyl amines (1 equiv). The reaction mixture was allowed to attain r.t. and stirring was continued for 2-3 h. Upon completion of the reaction (monitored by TLC), the reaction mixture was quenched with sat. aq NaHCO3 solution and extracted with EtOAc. The aqueous layer was saturated with solid NaCl and reextracted with EtOAc (2×). The combined extracts were washed sequentially with water and brine, and dried over anhydrous Na2SO4. Solvent was removed under vacuum, and the crude product was purified by flash chromatography (MeOH/CH2Cl2+0.1% NH4OH, 5:95) affording the corresponding Cbz-protected C2-alkylamino tetrahydrofuran derivatives 19a-c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine In ethanol at 80℃; for 12h; Inert atmosphere; | Synthesis of compound 7 To a solution of compound 4 (50 mg, 0.21 mmol) in EtOH (3 mL), n-decylamine (0.06 mL, 0.32 mmol) and Et3N (0.04 mL, 0.32mmol) were added. The reaction mixture was stirred at 80 °C for 12 h and progress of the reaction was monitored by TLC (3:2/EtOAc:Hexanes, Rf 0.20). The organic layer was removed under reduced pressure and the residue was purified by column chromatography(SiO2, 3:2/EtOAc:Hexanes) to afford compound 7 (75 mg, 91%) as a yellow liquid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃; for 4h; | 1.1 General procedure for thesynthesis of compounds 6a-6g General procedure: To a suspension of compound 5(10 mmol, 1 eq) in 1, 2-dichloroethane (30 mL) was added aliphatic amine (13mmol, 1.3 eq) and sodium triacetoxyborohydride (15 mmol, 1.5 eq) at RT, themixture was allowed to stir for 4 h, then quenched by addition of saturated NH4Claqueous solution. The mixture was extracted with ethyl acetate three times, theorganic layer was washed with brine, dried, and purified by flash columnchromatography to yield the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: (2R,3R,4S)-4-azido-3-(benzyloxy)tetrahydrofuran-2-carbaldehyde; 1-aminodecane In methanol at 20℃; for 3h; Stage #2: With sodium tetrahydroborate In methanol for 0.166667h; | 1.2 General procedure for the synthesis of compounds 6'a-6'g General procedure: To a suspension of compound5'(10 mmol, 1 eq) in methanol (20mL) was added aliphatic amine (11 mmol, 1.3 eq), the mixture was stirred for 3h at RT followed by adding sodium borohydride, the reaction mixture wasstirred for 10 min and quenchedwith 1 M NaOH. The mixture was evaporated and then extracted with ethyl acetatethree times, the organic layer was washed with brine, dried, and purified byflash column chromatography to yield the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: 1-aminodecane; (S)-1-N-boc-β-proline With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole In N,N-dimethyl-formamide for 0.0833333h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 3.5h; | S-70: tert-Butyl (S) -3- (Decylcarbamoyl)pyrrolidine-1- carboxylate. (S)-N-Boc-13-Proline (S-18, 10 mg, 0.047 rnniol, 1.0 equiv), decylamine (8.8 mg, 0.056 inmol, 1.2 equiv), HOAt (7.0 mg, 0.051 mmol, 1.1 equiv), and 2,6-lutidine (15.0 mg, 0.140 inmol, 3.00 equiv) were dissolved in anhydrous DMF (0.2 mL) . Upon dissolution of the reagents (about 5minutes), EDCIHCl (13.4 mg, 0.070 rmnol, 1.5 equiv) was added in one portion, and the reaction mixture was stirred at room temperature for 3.5 hours, after which it was poured into aqueous 1 N HC1 (2 mL) and EtOAc (3 mL) The aqueous phase was extracted with EtOAc (3 mL), and the combined organic phases were washed with aqueous 1 N Rd (2 mL), saturated aqueous NaHCO3 (2 mL), and saturated aqueous NaC1 (2 mL), sequentially. The organic phase was dried over Na2SO4, filtered and concentrated. Short path column chromatography (5i02, 5% MeOH/CH2C12) provided 14.7 mg (89%) of S-70. ‘H NMR (400 MHz, CDC13) 5 5.61 (br, 1H), 3.65 - 3.48 (m, 2H), 3.45 (dd, J= 13.5, 10.0 Hz, 1H), 3.34 - 3.20 (m, 3H), 2.85 - 2.75 (m, 1H), 2.18 - 2.00 (m, 2H), 1.54 -1.40 (m, 11H) , 1.33 - 1.19 (m, 14H) , 0.86 (t, J 8.5 Hz, 3H) |
89% | With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 1-aminodecane; (R)-1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole In N,N-dimethyl-formamide for 0.0833333h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 3.5h; | S-62 : tert-Butyl (R) -3- (Decylcarbamoyl)pyrrolidine1-carboxylate. (R)-N-Boc-f3-Proline (S-55, 10 mg, 0.047mrnol, 1.0 equiv), decylamine (8.8 mg, 0.056 mmol, 1.2 equiv), HOAt (7.0 mg, 0.051 mmol, 1.1 equiv), and 2,6-lutidine (15.0 mg, 0.140 mrnol, 3.00 equiv) were dissolved in DMF (0.2 mL) . Upon dissolution of the reagents (about 5 minutes), EDCIeHC1 (13.4 mg, 0.070 mmol, 1.5 equiv) was added in one portion, and the reaction mixture was stirred at room temperature for 3.5 hours, after which it was poured into aqueous 1 N HC1 (2 mL) and EtOAc (3 mL) . The aqueous phase was extracted with EtOAc (3 mL), and the combined organic phases were washed with aqueous 1 N HC1 (2 mL), saturated aqueous NaHCO3 (2 mL), and saturated aqueous NaCl (2 mL), sequentially. The organic phase was dried over Na2SO4, filtered and concentrated. Short path column chromatography (Si02, 5% MeOH/CH2C12) provided 18.3 mg (quant.) of S-62. ‘H NMR (400 MHz, CDC13) 5 5.67 (br, 1H), 3.63 - 3.48 (m, 2H), 3.44 (dd, J = 13.5, 10.0 Hz, 1H), 3.34 - 3.20 (m, 3H), 2.84 - 2.75 (m, 1H), 2.18 - 2.00 (m, 2H), 1.54 - 1.40 (m, 11H), 1.33 - 1.19 (m, 14H), 0.86 (t, J = 8.5 Hz, 3H) |
100% | With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 1-aminodecane; (3S,4S)-1-(tert-butoxycarbonyl)pyrrolidine-3,4-dicarboxylic acid With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole In N,N-dimethyl-formamide for 0.0833333h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 3.5h; | S-78: tert-Butyl (3S,4S)-3,4-Bis(decylcarbamoyl)- pyrrolidine-1-carboxylate (3S, 4S) -1- (tert-Butoxycarbonyl)pyrrolidine3,4-dicarboxylic acid ((S,S)-14, 8.0 mg, 0.031 mmol,1.0 equiv), decylamine (10.7 mg, 0.068 nimol, 2.2 equiv), HOAt (9.3 mg, 0.068 rnrnol, 2.2 equiv), and 2,6-lutidine (16.6 mg, 0.155 rnmol, 5.00 equiv) were dissolved in anhydrous DMF (0.15 mL) . Upon dissolution of the reagents (about 5 minutes), EDCIHCl (17.8 mg, 0.093 rnmol, 3.0 equiv) was added in one portion, and the reaction mixture was stirred at room temperature for 3.5 hours, after which it was poured into aqueous 1 N HC1 (2 mL) and EtOAc (3 mL) The aqueous phase was extracted with EtOAc (3 mL), and the combined organic phases were washed with aqueous 1 N MCi (2 mL), saturated aqueous NaHCO3 (2 mL), and saturated aqueous NaC1 (2 mL), sequentially. The organic phase was dried over Na2SO4, filtered and concentrated. Short path column chromatography (SiC2, 5% MeOH/CH2C12) provided 19.0 mg (quant.) of S-78. 1H NMR (400 MHz, CDC13) 6.32 (br, 1H), 6.15 (br, lH), 3.88 - 3.76 (m, 1H), 3.70 - 3.50 (m, 2H), 3.44 - 3.33 (m, 1H), 3.27 - 3.15 (m, 5H), 3.12 - 3.01 (m, 1H), 1.51 - 1.37 (m, 13H), 1.34 - 1.19 (m, 28H), 0.87 (t, J 7.6 Hz, 6H). |
100% | With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: C21H24N2O5S With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran for 4h; Cooling with ice; Stage #2: 1-aminodecane In tetrahydrofuran at 20℃; | 13 13. Synthesis of Compound 14 Compound 7 (50 mg, 0.12 mmol) was taken in an eggplant type bottle, 2 ml of THF was added to dissolve it completely, and the ice bath was slow.IBCF (45 [mu]l, 0.36 mmol), NMM (40 [mu]l, 0.36 mmol) was added dropwise and reacted in an ice bath for 4 hAfter adding decylamine (48 μl, 0.24 mmol), it was reacted overnight at room temperature. The solvent was then removed under reduced pressure and silica gel column chromatography gave a white solid, the compound.14 (yield 76%); |
Stage #1: C21H24N2O5S With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 4h; Stage #2: 1-aminodecane In tetrahydrofuran at 20℃; | (5a) General procedure: The compound 4 (50mg, 0.12mmol) was dissolved in anhydrous THF (2mL) and cooled to 0°C and then the IBCF (45μL, 0.36mmol), NMM (40μL, 0.36mmol) was added slowly, the mixture was stirred for 4 hours at 0°C, after that the ammonium hydroxide (9.2μL, 0.24mmol) was added, and stirred for overnight at RT. Then, the THF was removed under reduced pressure, the residue was purified by silica gel column chromatography (44.8mg, 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: C23H25NO6S With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.166667h; Stage #2: With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane for 0.166667h; Stage #3: 1-aminodecane In dichloromethane at 20℃; for 3h; | 2.9 9. Synthesis of Compound 30 Compound 23 (100 mg, 0.226 mmol) was taken in an eggplant type flask, about 4 ml of dried CH2Cl2 was added, and DIEA (78.60 μl, 0.451 mmol) was added after complete dissolution. After stirring for 10 min, HBTU (128.5 mg, 0.339 mmol) was added and stirred for 10 min. After adding decylamine (90 μl, 0.451 mmol), it was reacted for 3 h at room temperature. After the reaction was complete, about 40 ml of CH2Cl2 was added, and the mixture was washed twice with 10 ml of 1N HCl and then twice with saturated NaCl solution. The mixture was dried and concentrated over anhydrous Na2SO4 and then purified by silica gel column chromatography to give a white solid (yield: 80%). |
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane at 20℃; | (8a) General procedure: The compound 7 (100mg, 0.226mmol), DIEA (78.60μL, 451mmol) was dissolved in anhydrous CH2Cl2 (4mL), and then the HBTU (128.5mg, 0.339mmol) was added. The reaction mixture was stirred at room temperature until the TLC analysis showed that was complete consumption of the compound 7. The CH2Cl2 was removed under reduced pressure, the reaction mixture was dissolved in CH2Cl2 (100 mL) and washed successively with 1N HCl and saturated NaCl solutions, the organic layer was dried over Na2SO4 and concentrated. After that the reaction mixture was dissolved in THF:H2O (v:v=3:1) and cooled to 0, then the LiOH was added slowly. After stirring 10min at 0, the reaction was stopped with 10% citric acid solutions. The THF was removed under reduced pressure, the reaction mixture was diluted with CH2Cl2, and washed with saturated NaCl, and dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (83mg, 95%). found 429.1468. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With iron(II) triflate at 0 - 40℃; for 1h; Autoclave; | 9.B (B -1) The MPM (300 g, 2.5 mol, purity 99.9%) obtained in the step (a-1) was charged in a 1000 mL autoclave, the mixture was cooled to 0 ° C. and liquefied DMA (0.13 mol) of iron (II) trifluoromethanesulfonate as a metal complex, and stirred under a pressurized condition at 40 ° C. for 1 hour to perform sampling, and the reaction yield After confirming the rate (78%), the reaction was further carried out for 7 hours. After completion of the reaction, the temperature of the reaction solution was returned to room temperature, and it was confirmed by sampling that the reaction yield reached 99%. Thereafter, the reaction solution was transferred to a distillation apparatus, and recovery of unreacted raw materials and purification of the target product were carried out to obtain β-methoxy-N, N-dimethyl-propionic acid amide (abbreviation: MMPA) having a purity of 99.9% As a liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In acetonitrile at 70℃; | 8 4.3. General procedure for the synthesis of compounds 3-18 General procedure: To a solution of 2 (1.0 mmol) and K2CO3 (2.0 eq.) in CH3CN, amine (2.0 eq.) was added at room temperature. The resulting mixture was allowed to reflux for 1-5 h. The solvent was removed under reduced pressure and the mixture was extracted with CH2Cl2 and H2O and washed with brine solution. The organic layer was dried with Na2SO4, filtrated and concentrated under reduced pressure. Then, the crude mixture was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH) affording the desired compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96 %Chromat. | With platinum on carbon; sodium hydroxide at 150℃; for 36h; Inert atmosphere; Autoclave; | 2.4. Typical procedures of catalytic reactions General procedure: After the reduction under a flow of H2 at 300°C for 0.5h, we carried out catalytic tests without exposing the catalyst to air as follows. Methanol (30mmol) was injected to the reduced catalyst inside the glass tube through a septum inlet, thus the catalyst was covered with a layer of methanol to restrict it from air exposure. After removal of the septum under air, amine (1mmol), solid NaOH (1mmol), n-dodecane (0.25mmol) and a magnetic stirrer bar were placed in the tube. The tube was inserted into a stainless-steel autoclave (28cm3) and purged with N2 gas. Finally, the resulting mixture was heated at 150°C and stirred under 1barN2. For the model reaction of n-octylamine, the catalyst screening, optimization of reaction conditions, kinetic studies and control reactions, the conversion of n-octylamine and yields of products were determined by GC analyses, using n-dodecane as an internal standard by applying the GC sensitivity of the isolated or commercial products. For the substrate scope study, the products were isolated by column chromatography with silica gel 60 (spherical, 60-100μm, Kanto Chemical Co., Ltd.) using hexane/ethyl acetate or ethyl acetate/methanol as the eluting solvent. The yields of the isolated amine derivatives were determined and identified by 1H and 13C NMR and GC-MS methods. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With cesium fluoride In neat (no solvent) at 80℃; for 36h; | 2.3. General procedure for the synthesis of products 4-44 General procedure: To a mixture of 5-methoxypyrolidone 3 (17.4 mmol, 1 eq) and CsF(0.086 mmol, 5 mol%) was added the nucleophilic reactant (17.4 mmol,1 eq). The mixture was stirred under moderate vacuum (30 mmHg) at 80 °C, until the NMR conversion showed no more progression or aftercaking of the medium. Then, the crude product was precipitated byEt2O and recrystallized from EtOH or purified by flash liquid chromatography(silica gel, gradient of ethyl acetate in n-heptane), to affordthe target compounds. All products 4-44 were identified by comparingtheir spectral date with those of authentic samples or by elementalanalysis for new compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: carbon disulfide; 1-aminodecane With triton-B In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere; Stage #2: 4-(2-naphthyloxy)-1-chlorobutane In dimethyl sulfoxide for 0.666667h; Inert atmosphere; | Procedure for the preparation of dithiocarbamates ofω-substituted (2-naphthyloxy) alkanes General procedure: A mixture of desired amine (0.6 mL, 5 mmol) and carbon disulphide solution (3 mL,in excess) was taken in dry DMSO (35 mL). Triton-B (0.9 mL,4 mmol) was added in it and the reaction mixture was stirred at room temperature for 1 h. Now 2-(2-naphthyloxy)-1-chloroalkane(0.5 g, 2 mmol) was added in it and reaction was continued till its completion (2 h) as checked by TLC. Reaction mixtur ewas poured into distilled water (50 mL) and three-time extraction was done with ethyl acetate. After separation of organic layer, it was dried over anhydrous sodium sulphate and then concentrated to get dithiocarbamate of ω-substituted (2-naphthyloxy)alkanes. This compound was obtained as yellow solid (Scheme-II). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: carbon disulfide; 1-aminodecane With triton-B In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere; Stage #2: 3-(2-naphthyloxy)-1-chloropropane In dimethyl sulfoxide for 0.633333h; Inert atmosphere; | Procedure for the preparation of dithiocarbamates ofω-substituted (2-naphthyloxy) alkanes General procedure: A mixture of desired amine (0.6 mL, 5 mmol) and carbon disulphide solution (3 mL,in excess) was taken in dry DMSO (35 mL). Triton-B (0.9 mL,4 mmol) was added in it and the reaction mixture was stirred at room temperature for 1 h. Now 2-(2-naphthyloxy)-1-chloroalkane(0.5 g, 2 mmol) was added in it and reaction was continued till its completion (2 h) as checked by TLC. Reaction mixtur ewas poured into distilled water (50 mL) and three-time extraction was done with ethyl acetate. After separation of organic layer, it was dried over anhydrous sodium sulphate and then concentrated to get dithiocarbamate of ω-substituted (2-naphthyloxy)alkanes. This compound was obtained as yellow solid (Scheme-II). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: carbon disulfide; 1-aminodecane With triton-B In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere; Stage #2: 2-(2-naphthyloxy)-1-chloroethane In dimethyl sulfoxide for 0.666667h; Inert atmosphere; | Procedure for the preparation of dithiocarbamates ofω-substituted (2-naphthyloxy) alkanes General procedure: A mixture of desired amine (0.6 mL, 5 mmol) and carbon disulphide solution (3 mL,in excess) was taken in dry DMSO (35 mL). Triton-B (0.9 mL,4 mmol) was added in it and the reaction mixture was stirred at room temperature for 1 h. Now 2-(2-naphthyloxy)-1-chloroalkane(0.5 g, 2 mmol) was added in it and reaction was continued till its completion (2 h) as checked by TLC. Reaction mixtur ewas poured into distilled water (50 mL) and three-time extraction was done with ethyl acetate. After separation of organic layer, it was dried over anhydrous sodium sulphate and then concentrated to get dithiocarbamate of ω-substituted (2-naphthyloxy)alkanes. This compound was obtained as yellow solid (Scheme-II). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | 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 at 20℃; for 4.5h; | General procedure for the synthesis of compounds 9a-9n General procedure: 4-(6-Fluoro-1H-indol-3-yl)benzoic acid (8, 0.2 g, 0.78 mmol) was dissolved in DMF (10 mL), HATU (360 mg, 0.94 mmol) and DIPEA (302 mg, 2.34 mmol) were added, and the corresponding amine (0.94 mmol) was then added at room temperature. The mixture was stirred at room temperature for a time indicated in Table 1. After completion of the reaction (TLC), the mixture was quenched with water, and the precipitate was filtered off and washed with tert-butyl methyl ether-hexane. The reaction times, yields, and melting points of compounds 9a-9n are given in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine In acetonitrile at 20℃; for 0.166667h; | 3.3. General Procedure B: Synthesis of 4a-4al General procedure: A mixture of amine (0.5 mmol) or diamine (0.25 mmol), carbon disulfide (38 mg, 0.5 mmol),methyl (2-chloroacetyl)carbamate (76 mg, 0.5 mmol), and triethylamine (61 mg, 0.6 mmol) in MeCN(3 mL) was stirred at room temperature for 10 min. After disappearance of the reactant (monitoredby TLC), added 50 mL water to the mixture, then extracted with ethyl acetate 3 times (3 x 50 mL).The extract was dried over anhydrous Na2SO4 and evaporated. The residue was purified by columnchromatography on silica gel to give 4a-4al. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-aminodecane; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h; | Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-aminodecane; (3-chloropropyl)triethoxysilane at 78℃; for 60h; Stage #2: With sodium methylate In methanol | 5 Synthesis of 2,2-dimethoxy-1-n-butyl-1-aza-2-silacyclopentane General procedure: A flask equipped with a stirrer, a reflux condenser, a dropping funnel, and a thermometer was charged with 292.6 g (4.000 mol) of n-butylamine and heated to 78° C. After the internal temperature was stabilized, 198.7 g (1.000 mol) of chloropropyltrimethoxysilane was added dropwise over 10 hours, and the system was stirred at that temperature for 50 hours. After cooling the system to room temperature, n-butylamine hydrochloride generated by the reaction was removed by filtration to obtain 362.6 g of a precursor reaction solution. Next, a flask equipped with a stirrer, a reflux condenser, a fractionation head, and a thermometer was charged with 362.6 g of the precursor reaction solution and 3.8 g (0.020 mol) of a methanol solution of sodium methoxide (28% by weight sodium methoxide), and 136.3 g of a colorless transparent fraction having a boiling point of 47 to 48° C./0.2 kPa was obtained by performing distillation while distilling off generated methanol. The obtained fraction was subjected to 1H-NMR spectrum (deuterated chloroform solvent) measurement and IR spectrum measurement.The results are shown in FIGS. 1 and 2, respectively. From the above results, it was confirmed that the obtained fraction was 2,2-dimethoxy-1-n-butyl-1-aza-2-silacyclopentane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 1-aminodecane; C45H86O5 In 1,2-dichloro-ethane at 20℃; for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; for 72h; | 8 Synthesis of 8-2 A solution of 8-1 (1 eq., 1.15 g, 1.62 mmol) and 1-decylamine (1.5 eq, 2.43 mmol, 382 mg, 0.486 mL) in DCE (10 mL) was stirred at RT for about 15 min. To the solution was added sodium triacetoxyborohydride (1.5 eq., 2.43 mmol, 515 mg) and AcOH (1.5 eq, 2.43 mmol, 146 mg, 0.14 mL). The mixture was stirred at RT for 3 days. The reaction mixture was then concentrated. The residue was diluted with hexanes/EtOAc (99: 1) and washed with dilute NaOH solution, sat NaHC03 and brine. The organic extract was dried over sodium sulfate and was poured over a short column of silica gel. The column was eluted with a mixture of hexane, EtOAc and Et3N (95:5:0 to 80:20: 1). The fractions containing the pure product were combined and concentrated. The desired product was obtained as colorless oil (1.28 g, 1.51 mmol, 93%). 1HNMR (400 MHz, CDCI3) d: 3.97 (d, 5.8 Hz, 4H), 2.53 (t, 7.2 Hz, 2H), 2.43 (quintet-like, 5.5 Hz, 1H), 2.30 (t, 7.5 Hz, 4H), 1.68-1.57 (m, 6H), 1.49-1.40 (m, 2H), 1.40-1.08 (74H), 0.91-0.85 (m, 15H), 0.83-0.74 (br. 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: 1-aminodecane; C45H86O5 In 1,2-dichloro-ethane at 20℃; for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; for 48h; | 19 Synthesis of 19-2 A solution of 19-1 (1 eq., 0.493 g, 0.70 mmol) and 1-decylamine (1.5 eq, 1.05 mmol, 165 mg, 0.21 mL) in DCE (10 mL) was stirred at RT for about 15 min. To the solution was added sodium triacetoxyborohydride (1.5 eq., 1.05 mmol, 222 mg) and AcOH (1.5 eq, 1.05 mmol, 63 mg, 0.059 mL). The mixture was stirred at RT for 2 days. The reaction mixture was then concentrated. The residue was diluted with hexanes and washed with dilute NaOH, sat NaElCCh and brine. After the organic extract was dried over sodium sulfate, the solvent was removed under reduce pressure. The residue was taken up in a mixture of hexane, ethyl acetate and Et3N (80:20: 1) and was filtered through a short column of silica gel and washed with the same solvent mixture. Concentration of the filtrate gave the desired product as a colorless oil (582 mg, 0.69 mmol, 98%). The product was used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 1-aminodecane; C51H98O5 In 1,2-dichloro-ethane at 20℃; for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; for 48h; | 20 Synthesis of 20-2 A solution of the ketone 20-1 (0.92 g, 1.16 mmol) and 1-decylamine (2.03 mmol, 319 mg, 0.40 mL) in DCE (6 mL) was stirred at RT for 15 min, followed by addition of sodium triacetoxyborohydride (2.03 mmol, 429 mg) and AcOH (2.03 mmol, 121 mg, 0.115 mL). After the mixture was stirred at RT for 2 days, the reaction mixture was concentrated. The residue was diluted with hexanes and washed with dilute NaOH, saturated NaElCCh and brine. The organic phase was separated, dried over sodium sulfate. The extract was filtered through a short column of silica gel and the column was washed with a mixture of hexane/EtO Ac/Et3N, 95:5:0 to 80:20: 1). The desired product was obtained as a colorless oil (814 mg colorless oil, 0.87 mmol, 75% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With (1,3,5-triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 20 - 60℃; for 24h; Inert atmosphere; Autoclave; chemoselective reaction; | Carbonylative Amidation; General Procedure General procedure: 5′-O-(4,4′-Dimethoxytrityl)-5-iodo-2′-deoxyuridine (5′-O-DMT-5-IdU) (1a) (1.0 mmol, 656mg), the corresponding amine 2 (2.0 mmol), Pd(OAc)2 (2 mol%), PTABS ligand (4 mol%), Et3N (10 mmol) and N2-purged DMF (10 mL) were added to a 100 mL stainless steel autoclave reaction flask at room temperature. The autoclave was closed and flushed with nitrogen gas and then pressurized with CO gas (40 psi). Caution. Carbon monoxide (CO) is an odorless, colorless and highly toxic gas. The reactions should be carried out in efficient fume hoods fitted with CO detectors. The reaction mixture was stirred with a mechanical stirrer (500 rpm) and heated at 60 °C for 24 h. The mixture was then allowed to cool to room temperature and the CO was vented carefully in a fume hood by adding KMnO4 solution. The reaction mass was diluted in cold water and subsequently extracted with EtOAc (3 × 25 mL). The combined organic layer was dried over Na2SO4 and concentrated in vacuo. A slurry was prepared from the residue using silica gel and the product was isolated by column chromatography (60-120 neutralized silica gel; CHCl3/MeOH/Et3N, 97.5:2.0:0.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With formic acid In methanol; water Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-cyclohexylbutanoic acid 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 at 20℃; for 1.5h; Stage #2: 1-aminodecane In N,N-dimethyl-formamide at 20℃; for 20h; | General procedure E for amide coupling reaction using HATU for the preparation of intermediate compounds (72-99, 102, 105). General procedure: The carboxylic acid (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-cyclohexylbutanoic acid (71, 1 eq) and HATU (1.2 eq) were dissolved in DMF (8mL) and DIPEA (1.2 eq) was added. The solution was stirred at rtrt for 1.5h and the corresponding amine (1.2 eq) was added, either pure when liquid or diluted in DMF (4mL) when solid. The mixture was stirred for 20hat rt. CH2Cl2 or EtOAc (50mL) was added and the organic phase was washed 4 times with water (50mL) and dried over MgSO4. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography on silica (eluent: cyclohexane/EtOAc, CH2Cl2/MeOH or EtOAc/MeOH) if not stated otherwise. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: succinic acid anhydride; 1-aminodecane With triethylamine In N,N-dimethyl-formamide at 80℃; for 0.416667h; Stage #2: With acetic anhydride In N,N-dimethyl-formamide at 80℃; for 0.666667h; | 9 Succinic anhydride (30.5 g, 305 mmol) and N, N-dimethylformamide (100 ml) in a mixed solution of N, N-dimethylformamide (100 ml), decylamine (40 g, 254 mmol), and triethylamine (37.9 g, 375 mmol). ) Was added over 10 minutes and stirred at 80 ° C. for 15 minutes. Acetic acid anhydride (25.9 g, 254 mmol) was added dropwise over 10 minutes and stirred at 80 ° C. for 30 minutes. The reaction mixture was poured into water (500 ml), the precipitate was filtered and washed with distilled water. The crude product was purified by recrystallization with acetone. As a result, 54.8 g (229 mmol) of decylsuccinimide was obtained as a 90% white crystalline powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | Stage #1: N-Benzyloxycarbonyl-L-proline With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 1-aminodecane In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; | 3.4. General Procedure for the L-Proline-Organocatalysts Synthesis (3-16) General procedure: Ethyl chloroformate (1 equiv.) was added to a solution of protected-L-proline (1equiv.) and triethylamine (1 equiv.) in dry THF at 0 °C under nitrogen atmosphere. Thereaction mixture was stirred at 0 °C for 30 min. Then, a solution of amine (1 equiv.) in dryTHF was added, and the reaction mixture was stirred at 0 °C for 3 h, and afterwards, atroom temperature overnight. The mixture was filtered, and the volatiles were removedunder reduced pressure. The residual reagents were removed with acid-base extraction,and the product was purified by crystallization or column chromatography [53]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide at 50℃; Autoclave; chemoselective reaction; | 3.2. Aminocarbonylation of 6-Iodoquinoline (1) in the Presence of Various Amine Nucleophiles(a-w) under Atmospheric Carbon Monoxide Pressure General procedure: In a typical experiment, Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg,20.05 mmol) or XantPhos (14.5 mg, 0.025 mmol), 6-iodoquinoline (1) substrate (1 mmol),amine nucleophiles (amount of the amines are given in Tables 2 and 4) and triethylamine(0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL three-necked flasequipped with reflux condenser connected to a balloon filled with argon. The atmospherewas changed to carbon monoxide. The reaction was conducted for the given reactiontime upon stirring at 50C and analyzed by GC and GC-MS. The cooled reaction mixturewas then concentrated and evaporated to dryness under reduced pressure. The residuewas dissolved in chloroform (20 mL) and washed twice with water (20 mL). The organicphase was dried overNa2SO4,filtered, and evaporated under reduced pressure to a solidmaterial. All compounds were subjected to column chromatography (Silicagel 60 (Sigma),0.063-0.200 mm),CHCl3/MeOH, orCHCl3/EtOAc eluent mixtures (the exact ratios arespecified in the Characterization section found in the Supplementary file) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine In ethanol at 0 - 20℃; for 2h; Inert atmosphere; | 3.1.1. 3-(Decylamino)-4-ethoxycyclobut-3-ene-1,2-dione 6 To a solution of diethylsquarate (200 L, 1.35 mmol, 1 equiv.) in dry EtOH (12 mL) wasadded triethylamine (565 L, 4.05 mmol, 3 equiv.) at 0 C. Decylamine (270 L, 1.35 mmol,1 equiv.) was added dropwise to the reaction mixture at 0 C. The reaction mixture wasstirred at r.t. for 2 h, and then solvents were removed in vacuo. Flash chromatography of the residue (pure DCM) afforded 6 as a white solid (364 mg, 95% yield): Rf = 0.75(DCM/MeOH = 95/5); IR (film) 3261, 2926, 2854, 2250, 1804, 1706, 1611, 1525, 1492, 1457,1414, 1384, 1338, 1249, 1093, 1056, 916, 867, 732; 1H NMR 4.78 (q, JH5-H6 = 7.0 Hz, 2 H,H5), 3.42 (dd, JH10-NH = 13.5, JH10-H20 = 6.7 Hz, 2 H, H10 ), 1.64-1.56 (m, 2 H, H20 ), 1.46 (t,JH6-H5 = 7.0 Hz, 3 H, H6), 1.34-1.20 (m, 14 H, H30-H90 ), 0.87 (t, JH100-H90 = 6.9 Hz, 3 H, H100 );13C NMR 189.7 (C2), 182.7 (C1), 177.5 (C4), 172.5 (C2), 77.3 (C5), 69.7 (C10 ), 45.0 (C20 ), 31.9,30.6, 29.6, 29.3, 29.2, 26.4, 22.7 (C30-C90 ), 15.9 (C6), 14.2 (C100 ); HRMS (TOF MS ES+) calcd forC16H28NO3+ (M + H)+ 282.2064, found 282.20609. |
Tags: 2016-57-1 synthesis path| 2016-57-1 SDS| 2016-57-1 COA| 2016-57-1 purity| 2016-57-1 application| 2016-57-1 NMR| 2016-57-1 COA| 2016-57-1 structure
[ 6055-52-3 ]
Hexane-1,6-diamine dihydrochloride
Similarity: 0.91
[ 6055-52-3 ]
Hexane-1,6-diamine dihydrochloride
Similarity: 0.91
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 :