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. : | 2777-65-3 | MDL No. : | MFCD00014389 |
Formula : | C11H18O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OAOUTNMJEFWJPO-UHFFFAOYSA-N |
M.W : | 182.26 | Pubchem ID : | 31039 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.73 |
Num. rotatable bonds : | 8 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 54.92 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.05 cm/s |
Log Po/w (iLOGP) : | 2.29 |
Log Po/w (XLOGP3) : | 3.33 |
Log Po/w (WLOGP) : | 2.9 |
Log Po/w (MLOGP) : | 2.76 |
Log Po/w (SILICOS-IT) : | 2.89 |
Consensus Log Po/w : | 2.84 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.85 |
Log S (ESOL) : | -2.54 |
Solubility : | 0.526 mg/ml ; 0.00288 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.79 |
Solubility : | 0.0296 mg/ml ; 0.000162 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.57 |
Solubility : | 0.486 mg/ml ; 0.00267 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 2.59 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | 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 |
---|---|---|
96% | With toluene-4-sulfonic acid for 17h; Reflux; | |
95.4% | With sulfuric acid In methanol for 4h; Heating; | |
95% | With thionyl chloride at -15℃; |
95% | With thionyl chloride | |
87% | With thionyl chloride at -15 - 20℃; for 1h; Inert atmosphere; | |
72% | With thionyl chloride at 0℃; Reflux; | 3.9 Step 9:LNB reference no: GK-PHM-032A2Compound 9 Methyl-10-undecynoateFragment B[00158] Procedure: To a stirred solution of compound 9 (18 g, 98.9 mmol) in methanol(200 ml) was added SOCl2 (23.5 g, 197.8 mmol) drop wise at O0C then refluxed for overnight until the starting material disappeared on TLC. (20 % EtOAc in pet ether Rf.- 0.7).[00159] Work up: The reaction mixture was concentrated and extracted with DCM (200 ml) then washed with NaHCO3 solution, water (200 ml x 2) and brine (100 ml) then dried over anh.Na2SO4 and concentrated under reduced pressure to get crude compound which was further purified by column chromatography using silica gel (100 - 200 mesh) to afford Fragment B (14 g, 72 %) as a light yellow oil (GK-PHM-032A2).[00160] Characterization: 1U NMR (400 MHz, CDCl3) δ: 1.3 (m, 7H), 1.4 (m, 2H), 1.5- 1.6 (m, 2H), 1.7 (m, 2H), 2.1 (m, IH), 2.2 (m, IH), 2.3 (m, 2H). IR (cm"1): 634, 704, 741, 724, 1016, 1172, 1196, 1240, 1362, 1436, 1621, 1739, 2117, 2856, 2930, 3305, 3457. Mass: m/z = 197 (m+1) (Figs 62-64). |
With hydrogenchloride | ||
With hydrogenchloride zuletzt bei Siedetemperatur; | ||
With sulfuric acid at 25℃; | ||
With sulfuric acid | ||
With thionyl chloride | ||
With chloro-trimethyl-silane at 20℃; for 12h; | Synthesis of TAG; EPO The synthetic route to TAG was based on the method of Besra et al., Chem. Phys. Lipids (1993), 66, 23-34, and is set out in the Schematic Illustration below. The acetylenic carboxylic acid and trimethylsilyl chloride (0.1 eq.) in anhydrous methanol were mixed at room temperature for 12 hours. The reaction was evaporated to dryness to yield the pure carboxylic acid methyl ester product (Scheme 1, Step 1) as confirmed by TLC and 1HZ13C-NMR analysis and was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(II)-citrate; hexamethylenetetramine; hypophosphorous acid In water; N,N-dimethyl-formamide at 130℃; for 6h; Inert atmosphere; Green chemistry; chemoselective reaction; | |
With Lindlar's catalyst; ethyl acetate Hydrogenation; | ||
With Lindlar's catalyst; Petroleum ether Hydrogenation; |
With chloro-trimethyl-silane; acetic acid; triethylamine; benzo[1,3,2]dioxaborole 1.) THF, room temperature, 1 h, 2.) 65 - 70 deg C, 6 h; Yield given. Multistep reaction; | ||
With hydrogen In ethanol at 30℃; for 2h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride | ||
With oxalyl dichloride Heating; | ||
With thionyl chloride |
With phosphorus pentachloride In benzene Heating; | ||
With oxalyl dichloride for 3h; | ||
With thionyl chloride In chloroform | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 2h; | ||
With thionyl chloride In benzene for 2h; Heating; | ||
With oxalyl dichloride In dichloromethane | ||
With thionyl chloride In dichloromethane for 10h; Heating; | ||
With oxalyl dichloride In toluene for 2h; Heating; | ||
With thionyl chloride In N,N-dimethyl-formamide; toluene at 0 - 70℃; Inert atmosphere; | ||
With thionyl chloride for 3h; Reflux; | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h; | ||
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 15h; | ||
With thionyl chloride at 65℃; for 1h; | 1 4.3.1 N-(4-hydroxy-3-methoxybenzyl)undec-10-ynamide (2) Thionyl chloride (0.13mL, 1.8mmol) was added to (32 10-undecynoic acid (36.5mg, 0.2mmol) and refluxed at 65°C for 1h. Excess thionyl chloride was evaporated under argon and the crude product was dissolved in 1.5mL of 33 chloroform. In a separate flask, 34 water (2mL) and 35 sodium bicarbonate (67mg, 0.8mmol) was added to 36 3-hydroxy-4-methoxybenzylamine hydrochloride (38mg, 0.2mmol) and the mixture was stirred for 30min. Chloroform (1mL) was added and the flask was de-gassed. 37 Undec-10-ynoyl chloride was slowly added to the amine. The chloride flask was rinsed with a total of 1.5mL chloroform. The reaction was followed by TLC. The organic layer was separated and the aqueous layer was washed with chloroform 3×10mL). The organics were combined and washed with 1M HCl (50mL) followed by brine (50mL). The crude was dried, filtered and evaporated to afford 13 2 as an oil, 93% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With oxygen; ammonium chloride; copper(l) chloride In water at 20℃; | |
With hydrogenchloride; ammonium chloride; copper(l) chloride Reagens 4: Luft; | ||
With hydrogenchloride; ammonium chloride; copper(l) chloride Reagens 4: Kalium-hexacyanoferrat(III); |
With hydrogenchloride; oxygen; ammonium chloride; copper(l) chloride In ethanol | ||
With oxygen; copper dichloride | ||
With oxygen; copper(l) chloride | ||
With oxygen; ammonium chloride; copper(l) chloride In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium hydroxide In 1,2-dimethoxyethane for 12h; Heating; | |
75% | With PEG-200; potassium hydroxide at 125℃; for 2h; | |
75% | With potassium hydroxide; adogen 464 In cyclohexane for 24h; Heating; |
42% | With potassium hydroxide for 8h; Heating; | |
With diethyl ether; ammonia; sodium amide | ||
With potassium hydroxide at 150℃; | ||
With petroleum; sodium amide at 160℃; | ||
With potassium hydroxide at 150 - 160℃; | ||
With sodium amide | ||
With potassium hydroxide In propan-1-ol; water for 20h; Reflux; | 2.2.1. Synthesis of 10-undecynoic acid In a 1000 ml two-necked round bottom flask provided with a Teflon-coated magnetic bar and a pressure equalized dropping funnel, 10-undecenoic acid (46.0 g, 0.25 mol) and diethyl ether (500 mL) were placed. To this solution, bromine (48 g, 300 mmol) was added with stirring at 0 °C during 75 min. The mixture was allowed to warm up gradually to room temperature and after stirring overnight, the solvent and the excess of bromine were removed at reduced pressure. To a 2 L round-bottomed flask the brown liquid dibromo acid was transferred, n-propanol (800 mL) and 85 % aqueous potassium hydroxide (1.8 mol, 120 g in 140 ml water) were added and the mixture was refluxed for 20 h. Then, water (1500 mL) was added and the cold solution was neutralized with 2N (≈800 ml) hydrochloric acid solution. After several extractions with diethyl ether the combined organic phases were dried with anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was distilled under reduced pressure (0.5 mmHg) and the fraction at 120-130 °C was collected. The product solidifies on cooling and was recrystallized from hexane to obtain a white solid (yield 70%, mp 41-42 °C). 1H NMR (CDCl3, δ, ppm): 11.10 (s, 1H), 2.35 (t, 2H), 2.18 (dt, 2H), 1.94 (t, 1H), 1.67-1.29 (m, 12H). 13C NMR (CDCl3, δ, ppm): 180.6 (s), 84.9 (s), 68.3 (d), 34.3 (t), 28.5-24.8 (t), 18.5 (t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | Stage #1: undec-10-ynoic acid With n-butyllithium In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; cyclohexane at -78 - 0℃; for 2.5h; Stage #2: 1-Bromoheptane In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; cyclohexane at -78 - 20℃; for 18h; | 2.8.1. Octadec-10-ynoic acid (5) To a cooled (-78°C) solution of 10-undecynoic acid (1.00g, 5.49mmol) in anhydrous THF (40mL) and HMPA (10mL), was added dropwise via a syringe a 2.5M cyclohexane solution of BuLi (5.27mL, 13.2mmol) over a period of 30min. The mixture was wormed up to 0°C and kept at this temperature for 2h. The mixture was cooled again to -78°C and 1-bromoheptane (0.95mL, 6.04mmol) was injected. The whole was stirred at rt. for 18h before being quenched with 10% NH4Cl and 1M HCl solutions. The THF was removed in vacuo, and the residue was acidified to pH1 with 1M HCl and extracted twice with EtOAc. The organic layer washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified with flash chromatography on silica gel eluted with hexane-EtOAc (4:1) to give 5 (0.421g, 1.50mmol, 27%) as white crystals, mp 43°C, with 50% recovery of 10-undecynoic acid. 1H NMR (300MHz) δ 0.88 (3H, t, J=6.7Hz), 1.25-1.40 (16H, m), 1.40-1.54 (4H, m), 1.57-1.70 (2H, m), 2.14 (4H, t, J=7.0Hz), 2.35 (2H, t, J=7.62Hz), 9.96-10.42 (1H, br.). 13C NMR (100MHz) δ 14.00, 18.65, 22.55, 24.56, 28.69, 28.74, 28.76, 28.87, 28.93, 29.02, 29.07, 29.08, 29.70, 31.70, 33.97, 80.12, 80.29, 180.28. DART-MS m/z (rel intensity) 282 (26), 281 (100), 215 (17), 180 (16). HR-DART-MS [M+H]+ m/z 281.24840 (calcd for C18H33O2: 281.24806). |
(i) LiNH2, liq. NH3, (ii) /BRN= 1697160/; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(i) aq. NH2OH*HCl, CuCl2, EtNH2, KOH, (ii) /BRN= 1758339/, MeOH; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 15h; Inert atmosphere; | |
97% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere; | |
97% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | Undec-10-yn-1-ol [3b] Lithium aluminium hydride (0.19 g, 5.0 mmol) was added to dry THF (10 mL) at 0 °C under nitrogen atmosphere. Subsequently, undec-10-ynoic acid (0.46 g, 2.5 mmol) in dry THF (5 mL) was added dropwise over 20 minutes. The mixture was allowed to warm to room temperature, stirred for 2 hours and then quenched with ethyl acetate (5 mL) and water (5 mL). The mixture was filtered over a glass filter. The product was extracted with ethyl acetate (3 x 30 mL) and washed with and water (3 x 30 mL).The combined organic layers were dried with MgSO4, filtered andconcentrated under reduced pressure to yield 20 as pink oil (0.40 g, 2.4 mmol). Yield: 97%. Rf = 0.24 (1 : 10 ethyl acetate : petroleum ether). 1H NMR (500 MHz, CDCl3) δ 3.60 - 3.57 (t, J = 7.1Hz, 2H), 2.19 - 2.13 (td, J = 7.1, 2.6 Hz, 2H), 1.93 (t, J = 2.6Hz, 1H), 1.56 - 1.47 (m, 4H), 1.32 (m, 10H). 13C NMR (126 MHz, CDCl3) δ 84.7, 68.1, 62.8, 32.7, 29.4,29.3, 29.0, 28.7, 28.4, 25.7, 18.3. |
85% | With lithium aluminium tetrahydride In diethyl ether 25 deg C, 24 h, reflux, 3 h; | |
85% | With lithium aluminium tetrahydride In diethyl ether at 40℃; for 3h; | |
84% | With lithium aluminium tetrahydride In diethyl ether for 4h; Heating; | |
63% | With lithium aluminium tetrahydride In diethyl ether at 0℃; for 4h; | |
With lithium aluminium tetrahydride | ||
Multi-step reaction with 2 steps 1: 95.4 percent / conc.H2SO4 / methanol / 4 h / Heating 2: 91.6 percent / LAH / diethyl ether / 2 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: HCl / zuletzt bei Siedetemperatur 2: sodium; butyl alcohol | ||
With lithium aluminium tetrahydride | ||
Multi-step reaction with 2 steps 1: 12 h / 20 °C 2: lithium aluminium tetrahydride / 4 h / 20 °C | ||
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide In diethylene glycol Heating; | ||
Multi-step reaction with 2 steps 1: [AuCl(IPr)]; Ag(1+)*C2HF3O2 / water; isopropyl alcohol / 48 h / 70 °C / Sealed tube; Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 10 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: undec-10-ynoic acid With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; Stage #2: heptanal In tetrahydrofuran; hexane at -78 - 20℃; for 1.5h; | 2.8.7 12-Hydroxyoctadec-10-ynoic acid (10) To a cooled (-78°C) and stirred solution of 10-undecynoic acid (424mg, 2.33mmol) in dry THF (24mL), was added dropwise a 2.5M solution of BuLi in hexane (2.05mL, 5.12mmol). After 10min at that temperature, the cooling bath was removed and the whole was stirred at rt. for 45min. The mixture was cooled again to -78°C and heptanal (293mg, 2.56mmol) dissolved in THF (2mL) was injected. The cooling bath was removed and the mixture was stirred at rt. for 1.5h. The reaction was then quenched with 2M HCl solution and extracted twice with ether. The ethereal extracts were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by silica gel column chromatography eluted with hexane-EtOAc (2:1) to give 10 (332mg, 1.12mmol, 48%) as white crystals, mp 35-36.5°C. 1H NMR (300MHz) δ 0.88 (3H, t, J=6.5Hz), 1.22-1.55 (18H, m), 1.58-1.72 (4H, m), 2.20 (2H, dt, J=6.8, 1.8Hz), 2.34 (2H, t, J=7.6Hz), 4.36 (1H, dt, J=6.5, 1.8Hz), 5.50-6.52 (2H, br). 13C NMR (125MHz) δ 14.02, 18.57, 22.53, 24.53, 25.11, 28.50, 28.53, 28.69, 28.77, 28.89, 28.92, 31.72, 33.97, 38.05, 62.68, 81.21, 85.36, 179.47. |
With ethylmagnesium bromide; copper(l) cyanide 1.) tetrahydrofuran, 20 deg C, 2 h, 2.) reflux, 24 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; bromine 1) CCl4, r.t., 2) 135-145 deg C, 4 h; Yield given. Multistep reaction; | ||
Stage #1: Methyl 10-undecenoate With bromine In chloroform at 20℃; for 2h; Stage #2: With potassium hydroxide In ethanol at 80℃; for 3h; Stage #3: With hydrogenchloride In water | 3.8 Step 8:LNB Reference No: GK-PHM-030A1 [00155] Procedure: To a stirred solution of compound 8 (25 g, 126.26 mmol) in chloroform (100 ml) was added bromine (30 ml, 631 mmol) dropwise and stirred for 2 h at RT. Then it was concentrated under reduced pressure and the residue was dissolved in ethanol (200 ml), added KOH (90 g) and stirred for 3 h at 800C until the starting material disappeared on TLC (20 % EtOAc in pet ether Rf= 0.6).[00156] Work up: The reaction mixture was concentrated under reduced pressure, obtained crude was acidified with 6N HCl (30 ml), and extracted with ethyl acetate (350 ml). The organic layer was washed with water (100 ml) and brine (100 ml), dried over anhyd Na2SO4 and evaporated under reduced pressure to afford compound 9 (18 g, 78 %) as a light brown oil (GK-PHM-030A1). It was directly used in the next step without any further purification.[00157] Characterization: 1H NMR (400 MHz, CDCl3) δ: 1.3 (m, 9H), 1.5 (m, 2H), 1.6-1.7 (m, 2H), 2.0 (m, IH), 2.2 (m, IH), 2.4 (m, 2H). Mass: m/z = 183 (m+1) (Figs 59-61). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With lithium hydroxide In tetrahydrofuran; water at 20℃; for 24h; | Undec-10-ynoic acid [2] methyl-10-undecynoate (0.49 mL,2.5 mmol) was added to a solution of lithium hydroxide (0.29 g, 12 mmol) in a 1: 3 mixture of water : THF (25 mL). The yellow mixture was stirred at RT for 24 hours and then acidified with 1N aqueous HCl (20 mL). The product was extracted with ethyl acetate (2 x 20 mL) and washed with 1N aqueous HCl (2 x 20 mL) andwater (20 mL). The combined organic layers were dried with MgSO4, filtered and concentrated under reduced pressure to yield 19 as purple crystals (0.46 g, 2.5 mmol). Yield: 100%. Rf= 0.25 (1 : 5 ethyl acetate : petroleumether). 1H NMR (500 MHz, CDCl3) δ 2.34 (t, J= 6.8 Hz, 2H), 2.17 (td, J = 7.1, 2.6 Hz, 2H), 1.94 (t, J = 2.6Hz, 1H), 1.65 - 1.61 (p, J = 7.4 Hz, 2H), 1.55 - 1.48 (quint, J =7.4 Hz, 2H), 1.40 - 1.30 (m, 8H). 13C NMR (126 MHz, CDCl3)δ180.4, 84.6, 68.1, 34.1, 29.1, 28.9, 28.8, 28.6, 28.4, 24.6, 18.3. |
With potassium hydroxide for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With potassium hydroxide; methylamine; copper(l) chloride In tetrahydrofuran; methanol; water 1) 20 deg C, 4 h, 2) 40 deg C, 1 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; sodium 1.) Et2O, -20 deg C, 2.) liq. NH3, 30 min; Yield given. Multistep reaction; | ||
Multi-step reaction with 2 steps 1: 94 percent / Br2 / diethyl ether / 2 h / 5 °C 2: 75 percent / KOH, Adogen 464 / cyclohexane / 24 h / Heating | ||
Multi-step reaction with 2 steps 1: chloroform; bromine 2: ethanolic KOH-solution / 150 °C |
With hydrogenchloride; potassium hydroxide; bromine In diethyl ether; ethanol | A STEP A. 10-Undecynoic Acid STEP A. 10-Undecynoic Acid To 10-Undecenoic acid (100 g, 0.54 mol) dissolved in 400 mL diethyl ether was added 30 mL (93.6 g, 0.58 mol) Br2 at a rate so as to maintain gentle reflux. After the addition was complete, the ether was removed under reduced pressure to yield a clear, pale yellow oil of the dibromide. This material was dissolved in 400 mL anhydrous ethanol and added to a solution of 250 g of 85 percent KOH (213 g KOH, 3.78 mol) in one L anhydrous ethanol. The heterogeneous suspension was warmed under reflux overnight, and then cooled to room temperature. The reaction mixture was neutralized to pH~1 by cautious addition of 12N HCl, and poured onto 4 L of ice. The semisolid product was extracted with ether, washed with H2 O and saturated aqueous sodium chloride, dried over Na2 SO4, and the ether removed under reduced pressure. The residue was distilled under vacuum. The fraction, b.p. 120°-130°/0.6 Torr, which crystallized on standing, contained the product (59.3 g, 60%); nmr (CDCl3); 1.3δ(m, 12 H, CH2), 1.93 t, J=2.5 Hz, 1 H, =CH), 2.14 (m, 2 H, =CCH2), 2.32 (t, J=7 Hz, 2 H, CH2 C=O); Ir (film) 3350 cm-1(V=CH) 2130 (νC=C), 3500-2500 (br, ν OH), 1710 (νC=O). | |
Multi-step reaction with 2 steps 1: bromine / diethyl ether / 0 - 20 °C 2: potassium hydroxide / propan-1-ol; water / 20 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; | |
63% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; | 5 [0331] An alkyne dye as shown in 5of Figure 13, Panel Aand in chemical structure 5 below was synthesized byadding EDCI (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) (83 mg, 0.43 mmol, 1, equiv.) to a solutionof fluoresceinamine (150 mg, 0.43 mmol, 1 equiv.) and 10-undecynoic acid (79 mg, 0.43, 1 equiv.) in pyridine (2 mL) atroom temperature. The suspension was stirred overnight and the reaction mixture was poured into H2O (15 mL). Thesolution was acidified (pH < 2) by adding conc. HCl. After stirring for 1 h, the precipitate was filtered off, washed withH2O (5 mL) and dissolved in small amount of EtOAc. Addition of hexanes led to the precipitation of 5of Figure 13, PanelA as orange crystals, which were collected and dried under vacuum (138 mg, 63%). The analytical data are identicalwith those reported in the literature. See, e.g.,Crisp, G. T.; & Gore, J. (1997) Tetrahedron 53:1505-1522. An exampleof a structure of an alkyne dye is shown in chemical structure 5: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With acetylacetonatodicarbonylrhodium(l); johnphos In tetrahydrofuran at 40℃; for 24h; | |
94% | With triethylamine; johnphos In tetrahydrofuran at 40℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In tetrahydrofuran at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine In tetrahydrofuran at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 87 percent / C2H5NH2, NH2OH*HCl / CuCl / methanol / 0.25 h 2: 98 percent / H2 / PtO2 / methanol / 1 h / 760 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethylphosphine In diethyl ether at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper diacetate; sodium L-ascorbate In water; <i>tert</i>-butyl alcohol at 20℃; for 23h; regiospecific reaction; | |
78% | With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 14h; | Generalprocedure for the synthesis of triazoles General procedure: To a 50 mL ofround bottom flask 100 mg of azide 3(100 mg, 0.26 mmol) and 4-pentynoic acid (55 mg, 0.33 mmol)were dissolved in tBuOH:THF:Water/1:1:1 (6 mL).To this solution copper (II) sulfate (8 mg, 0.052 mmol) and L-ascorbic sodium salt (21 mg, 0.104 mmol) were added. Reactionwas kept at room temperature for 14h. Reactionwas monitored using TLC and LC-MS, shows the conversion by this time. Thesolvents were evaporated under reduced pressure. The resulting residue wasdissolved in chloroform (10 mL), washed with water (2 mL) and the extractedcrude product was purified using flash chromatography DCM:MeOH ( 95:5) toafford the desired product compound 5 as asolid of 0.120 g (82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-carbodiimide | ||
With dicyclohexyl-carbodiimide In dichloromethane at 0 - 23℃; for 16h; Inert atmosphere; | 4.1.1. General procedure for synthesis of NHS esters (method A) General procedure: To a solution of the appropriate fatty acid 9b, 13b-37b (1.0equiv) in CH2Cl2 (0.1 M) at 0°C was added N-hydroxysuccinimide (NHS, 1.0 equiv) and N,N'-dicyclohexylcarbodiimide (1.0 equiv). The reaction mixture was warmed to 23°C and stirred 16 h. Theresulting mixture was filtered and the filtrate was concentrated under reduced pressure to provide NHS esters 9c, 13c-37c without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 15h; Inert atmosphere; | |
99% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 15h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 15h; Inert atmosphere; | |
65% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 15h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With ammonium peroxydisulfate; silver nitrate In water; acetonitrile at 100℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; | 4.1.8. General procedure for the preparation of tubulyzine derivatives (9a-e) General procedure: A solution of 7 (1 g, 2.4 mmol), 4-pentinoic acid (0.27 g, 2.6 mmol), DCC (0.7 g, 3.1 mmol) and DMAP (0.37 g, 3 mmol) in THF (4 ml) was stirred for 24 h at room temperature under nitrogen atmosphere. The solvent was removed and the residue was purified by flash chromatography on silica gel (EtOAc/pentane, 1:1, then EtOAc) to give 2,4-di(4'-methoxybenzylamino)-6-[2'-(4-pentynoyloxy)ethylamino]-1,3,5-triazine 9a (1.12 g, 2.3 mmol, 96%) as a white oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran at 80 - 85℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With formic acid; F6P(1-)*C16H22N3Ru(1+); water In 1-methyl-pyrrolidin-2-one at 25℃; for 48h; Inert atmosphere; Sealed tube; | |
80% | With [2,2]bipyridinyl; formic acid; cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate; water In tetrahydrofuran at 80℃; for 48h; | |
80% | With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); Ru(Cp)(PPh<SUB>2</SUB>Py<SUP>tBu</SUP>)<SUB>2</SUB>(MeCN)PF<SUB>6</SUB>; water In isopropyl alcohol at 70℃; for 48h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With [AuCl(IPr)]; Ag(1+)*C2HF3O2 In water; isopropyl alcohol at 70℃; for 48h; Sealed tube; Inert atmosphere; | |
80% | With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); Au(IPr)Cl; water; silver trifluoroacetate In isopropyl alcohol at 70℃; for 48h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: thionyl chloride / 3 h / Reflux 2: trimethylsilylazide / toluene / 2 h / Reflux | ||
With diphenylphosphoranyl azide; triethylamine In tetrahydrofuran at 60℃; for 3h; | ||
With diphenyl phosphoryl azide; triethylamine In benzene at 80℃; for 1h; | 3.1.5. Benzyl dec-9-ynylcarbamate (16) A mixture of 10-undecynoic acid 16 (1 g, 5.49 mmol), DPPA (1.42 mL, 6.58 mmol) andtriethylamine (0.9 mL, 6.58 mmol), was refluxed in benzene (20 mL) for 1 h. Upon theformation of the intermediate (monitored by TLC), benzyl alcohol (1.25 mL, 12.06 mmol)was added and the reaction mixture was heated at 80 C overnight. Then, the solvent wasremoved in vacuo and the residue was diluted with EtOAc, washed with 0.4 N HCl andaq. saturated NaHCO3. Pure 16 was obtained after FCC purification (Hex/EtOAc = 98:2).Light yellow oil; yield: 1.04 g, 66%; 1H-NMR (300 MHz, CDCl3) d 7.37-7.30 (m, 5H), 5.09 (s,2H), 4.73 (br.s, 1H), 3.26-3.15 (m, 2H), 2.17 (dt, J = 7.0 and 2.6 Hz, 2H), 1.95-1.93 (m, 1H),1.54-1.49 (m, 4H), 1.39-1.30 (m, 8H); 13C-NMR (75 MHz, CDCl3) d 156.4, 136.8, 130.0, 128.8(2C, Aryl), 128.7 (2C, Aryl), 84.8, 68.3, 66.7, 41.2, 30.1, 29.2, 29.1, 28.8, 28.7, 28.6, 18.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 1,4-diisocyanatobenzene; triethylamine In tetrahydrofuran at 80℃; | Synthesis of 3,5-disubstituted isoxazole derivative of longchain alkynoic acid (6). 4.2.1.2. 1,4-Phenylene diisocyanate (0.003 mol)wasadded to long chain alkynoic acid (1) (0.001 mol) in dry tetrahydrofuran(THF) (20 ml). Triethylamine (0.003 mol)was added to thereaction mixture and this was heated to 80 C. Nitrobutane(0.003 mol) was added in portions over a period of 6e8 h, and thenthe reaction was heated for additional 2 h. The precipitate wasobserved. After heating, the reaction mixture was cooled. The reactionwas quenched with water (z6 ml) and then allowed to stirat room temperature for 1 h. The polyurea (polymer) was removedby filtration and washed with THF. The solvent was evaporated on awater bath and then worked up with diethyl ether-water. Further,product (6) was purified by silica gel column with petroleum ether/diethyl ether as eluent. The characterization data of novel compound(6) are given below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 6h; Inert atmosphere; | Monomer 2, C18H6(OC5H11)5(OOCC8H16-C≡CH) Monomer 2 was prepared similar to the reported method [52]. The mixture of 10-undecynoic acid (218 mg, 1.2 mmol), dicyclohexylcarbodiimide (DCC, 247 mg, 1.2 mmol), 4-N,N-dimethylaminopyridine (DMAP, 67 mg), and 2-hydroxy-3,6,7,10,11-pentakis(pentyloxy)triphenylene (1, 674 mg, 1.0 mmol) in CH2Cl2 (20 mL) was stirred at room temperature for 6 h under a nitrogen atmosphere. After the reaction was finished, water was added to the mixture and then extracted with CH2Cl2. The extract was dried with MgSO4 and the solvent was distilled off using a rotary evaporator. The crude product was purified by column chromatography on silica gel eluted with CH2Cl2/hexane (3:2 in volume). The product was re-crystallized from ethanol affording a white solid (543 mg, 0.65 mmol, 65%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.6% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | 2.6; 26; 5; 29 tert-butyl 4-(undec-10-ynoyl)piperazine-1-carboxylate (6). To a stirring solution of 10-undecynoic acid (1.18 g, 6.48 mmol), HBTU (2.45 g, 6.48 mmol) and Et3N (0.9 mL, 6.48 mmol) in DCM (10 mL) was added 1-Boc-piperazine (1.0 g, 5.4 mmol). The reaction mixture was stirred overnight at room temperature. The resulting mixture was diluted with dichloromethane and then washed with saturated aHC03 and brine. Thecombined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (Hexanes/EtOAc, 3: 1) to afford compound 6 as a yellow syrup (1.6 g, 84.6% yield). 1H NMR (400 MHz, CDC13) δ 1.15-1.30 (m, 8H), 1.34 (s, 9H), 1.36-1.54 (m, 4H), 1.82 (td, J= 0.8, 2.4, 1H), 2.04 (td, J=2.4, 7.2, 2H), 2.20 (t, J=7.2, 2H), 3.27 (t, J=5.2, 2H), 3.32 (s, 4H), 3.46 (t, J=5.2, 2H). 13C NMR (100 MHz, CDC13) δ 18.06, 24.95, 28.08, 28.12, 28.35, 28.62, 28.96, 29.06, 33.01, 41.03, 45.12, 67.94, 79.91, 84.33, 154.26, 171.53. |
84.6% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | tert-Butyl 4-(undec-10-ynoyl)piperazine-1-carboxylate (6) To a stirring solution of 10-undecynoic acid (1.18 g, 6.48 mmol), HBTU (2.45 g, 6.48 mmol) and Et3N (0.9 mL, 6.48 mmol) in DCM (10 mL) was added 1-Boc-piperazine (1.0 g, 5.4 mmol). The reaction mixture was stirred overnight at room temperature. The resulting mixture was diluted with dichloromethane and then washed with saturated NaHCO3 and brine. The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (Hexanes/EtOAc, 3:1) to afford compound 6 as a yellow syrup (1.6 g, 84.6% yield). 1H NMR (400 MHz, CDCl3) δ 1.15-1.30 (m, 8H), 1.34 (s, 9H), 1.36-1.54 (m, 4H), 1.82 (td, J= 0.8, 2.4, 1H), 2.04 (td, J= 2.4, 7.2, 2H), 2.20 (t, J= 7.2, 2H), 3.27 (t, J= 5.2, 2H), 3.32 (s, 4H), 3.46 (t, J= 5.2, 2H). 13C NMR (100 MHz, CDCl3) δ 18.06, 24.95, 28.08, 28.12, 28.35, 28.62, 28.96, 29.06, 33.01, 41.03, 45.12, 67.94, 79.91, 84.33, 154.26, 171.53. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In dichloromethane at 20℃; for 18h; Inert atmosphere; | General procedure for esterification using diphenylmethyl imidate and cinnamic acid as an example: General procedure: Cinnamic acid (0.200 g, 1.35 mmol) and diphenylmethyl trichloroacetimidate (0.580 g, 1.76 mmol)were added to a flame dried round bottom flask. Dry dichloromethane (5.4 mL) was then added and the reaction was stirred under argon for 18 h. Triethylamine (0.5 mL) was then added the reaction mixture was preadsorbed on silica gel. Purification by silica gel chromatography using 1% triethylamine 5% ethyl acetate/94% hexanes provided 0.401 g (93%) of the diphenylmethyl cinnamate 13 as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 35℃; Schlenk technique; Inert atmosphere; | 3-Acyl-4-hydroxycoumarins 6-12 and 14; General Procedure General procedure: 4-hydroxycoumarin (1 equiv) and DMAP (0.5 equiv) were dissolved in DMF (3 mL) at 0°C. Acid (1.5 equiv) and EDC·HCl (1.5equiv) were dissolved in DMF (3 mL) in a Schlenk flask under argon.The mixture was stirred at 0°C (30 min) and added via syringe to the flask containing 4-hydroxycoumarin and DMAP. The mixture was stirred at 0°C (1 h) and then at 35°C until complete coumarin consumption (TLC). The solvent was removed under reduced pressure at 50°C and the residue was dissolved in water and extracted with CH2Cl2. The combined organic phases were washed with 0.05 M NaOH, and the solvent was removed under reduced pressure. The product was purified by column chromatography (EtOAc-petroleum ether) to give products 6-12 and 14. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 35℃; Schlenk technique; Inert atmosphere; | 3-Acyl-4-hydroxycoumarins 6-12 and 14; General Procedure General procedure: 4-hydroxycoumarin (1 equiv) and DMAP (0.5 equiv) were dissolved in DMF (3 mL) at 0°C. Acid (1.5 equiv) and EDC·HCl (1.5equiv) were dissolved in DMF (3 mL) in a Schlenk flask under argon.The mixture was stirred at 0°C (30 min) and added via syringe to the flask containing 4-hydroxycoumarin and DMAP. The mixture was stirred at 0°C (1 h) and then at 35°C until complete coumarin consumption (TLC). The solvent was removed under reduced pressure at 50°C and the residue was dissolved in water and extracted with CH2Cl2. The combined organic phases were washed with 0.05 M NaOH, and the solvent was removed under reduced pressure. The product was purified by column chromatography (EtOAc-petroleum ether) to give products 6-12 and 14. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 14h; | General procedure for the synthesis of triazoles using compound 11 as an example To a 50 mL round bottom flask 100 mg of azide (100 mg, 0.26 mmol) and 10-undecynoic acid (62 mg, 0.34 mmol) were dissolved in tBuOH:THF:Water: 1:1:1 (6 mL). To this solution copper (II) sulfate (8 mg, 0.052 mmol) and L-ascorbic sodium salt (21 mg, 0.104 mmol) were added. Reaction was stirring at room temperature for typically 14h. Reaction was monitored using TLC and LC-MS. The solvents were evaporated under reduced pressure. The resulting residue was dissolved in chloroform (10 mL), washed with water (2 mL) and the crude product was purified using flash chromatography on silica gel by EtOAc:Hexane (95:5) or DCM:MeOH (97:3). The desired product 11 was obtained as a white solid (0.114 g, 81%). The other compounds were synthesized and purified similarly. The characterization data are given below for these compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 2,2'-azobis(isobutyronitrile) In toluene at 80℃; for 0.333333h; | 2.2.2. Thiol-yne addition to 10-undecynoic acid A mixture of 10-undecynoic acid (1.00 g, 5.50 mmol) and 2-mercaptoethanol (0.45 g, 5.77 mmol) was heated in toluene solution at 80 °C in presence of AIBN (10% mol init./mol C≡C) for 20 min. The product was purified by column chromatography using hexane-ethyl acetate 1:1 as eluent to afford a mixture of E and Z vinylsulfides as a white solid (yield 77%, mp: 35-36 °C, E/Z ratio 1:1 from 1H NMR). 1H NMR (CDCl3, δ, ppm): 5.90-5.84 (2dt, 1H), 5.79-5.58 (2dt, 1H) Jtrans=14.8 Hz, Jvec=8 Hz, Jcis=8.8 Hz, Jvec=8 Hz, 3.75 (dt, 2H), 2.84 (dt, 2H), 2.34 (t, 2H), 2.16-2.03 (dq, 2H), 1.66 (m, 2H), 1.42-1.25 (m, 10H). 13C NMR (CDCl3, δ, ppm): 179.9 (s), 133.9 (d), 131.6 (d), 123.7 (d), 121.3 (d), 61.4 (t), 60.8 (t), 36.9 (t), 36.2 (t), 34.2 (t), 33.2 (t), 29.4-24.8 (t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 48h; | Chemical Syntheses of 1-Myristoyl-2-(10-undecynoyl)-snglycero-3-phospho-2-(3-methyl-3H-diazirin-3-yl)ethanol (pac-PC) 1-Myristoyl-sn-glycero-3-phosphatidyl-2-(3-methyl-3H-diazirin-3-yl)ethanol (20 mg, 0.043 mmol), 10-undecynoic acid (40 mg, 0.22 mmol), N,N-dicyclohexylcarbodiimide (26 mg, 0.126 mmol), and 4-dimethylaminopyridine (5 mg, 0.043 mmol) were dissolved in 2 ml of anhydrous chloroform and stirred at room temperature for 48 h. Solvents were removed by rotary evaporation.The crude product was purified on a silica gel column eluted with 10% methanol in chloroform to deliver the final product (20.4 mg, yield 75%, Rf = 0.36 with 20% methanol in chloroform). 1H NMR (600 MHz, CDCl3) 5.28 (br, 1H), 4.35 (br, 2H), 4.14 (br, 2H), 4.02 (br, 1H), 3.82 (br, 1H), 2.40-2.20 (4H), 2.20-2.10 (2H), 1.92 (m, 1H), 1.70-1.55 (6H), 1.50 (m, 2H), 1.30-1.10 (28H), 1.04 (s, 3H), 0.86 (t, 3H). Negative ESI-MS/MS analysis yielded the following diagnostic parent and fragment ions: m/z 627.7 [M - H]-; m/z 599.5, 435.5, 228.3, 182.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(II) sulfate; sodium L-ascorbate; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol In water; dimethyl sulfoxide at 20℃; | ||
With copper(ll) sulfate pentahydrate; sodium L-ascorbate In ethanol; water at 20℃; for 12h; | Preparation of triazole derivatives (Route I) General procedure: In a flask, azide (1 mmol), 10-undecynoic acid (1 mmol) were mixed in water and ethanol (v/v = 1:1, 14 mL). Sodium ascorbate (0.10 mmol) of freshly prepared 1 mol/L solution in water was added, followed by the addition of CuSO4·5H2O in water (0.05 mmol). The mixture was stirred overnight at room temperature. The solvent was removed and the crude product was purified by column using DCM/MeOH = 100:1-20:1 as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Inert atmosphere; | 4.7. A general procedure for the synthesis of triazole derivatives General procedure: Hepta-O-acetyl-b-lactosyl azide 6I, 100 mg was dissolved in 4.5 mL mixture of t-BuOH: H2O: THF (1:1:1), the corresponding alkyne (1.2 mmol), copper sulphate (0.2 mmol) and sodium ascorbate (0.4 mmol) were also added. The reaction mixture was stirred at room temperature for 24 h and monitored by TLC, NMR and LCMS. The mixture was concentrated and diluted with DCM and washed with water. The organic phase was dried over sodium sulphate, filtered and concentrated. The crude products were purified by flash chromatography on silica gel using a gradient of 0.5%MeOH/DCM to 5% MeOH/DCM. The same procedure was also used for the synthesis of the hepta-O-acetyl-β-maltosyl triazole derivatives, 50 mg of the starting material hepta-O-acetyl-β-maltosylazide 6II was used. The yields of the isolated pure products and their characterization data are given for each compound. The following are the characterization data for the triazole compounds synthesized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Inert atmosphere; | 4.7. A general procedure for the synthesis of triazole derivatives General procedure: Hepta-O-acetyl-b-lactosyl azide 6I, 100 mg was dissolved in 4.5 mL mixture of t-BuOH: H2O: THF (1:1:1), the corresponding alkyne (1.2 mmol), copper sulphate (0.2 mmol) and sodium ascorbate (0.4 mmol) were also added. The reaction mixture was stirred at room temperature for 24 h and monitored by TLC, NMR and LCMS. The mixture was concentrated and diluted with DCM and washed with water. The organic phase was dried over sodium sulphate, filtered and concentrated. The crude products were purified by flash chromatography on silica gel using a gradient of 0.5%MeOH/DCM to 5% MeOH/DCM. The same procedure was also used for the synthesis of the hepta-O-acetyl-β-maltosyl triazole derivatives, 50 mg of the starting material hepta-O-acetyl-β-maltosylazide 6II was used. The yields of the isolated pure products and their characterization data are given for each compound. The following are the characterization data for the triazole compounds synthesized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.03% | With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere; | 28 Synthesis of Intermediate K Example 28-Synthesis of Intermediate K Under N2 protection, undec-10-ynoic acid (500.00 mg, 2.74 mmol) and (2R,3R,4S,5S,6R)-2-[(2S,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)tetrahydrofuran-2-yl]oxy-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol (1.88 g, 5.48 mmol) and diisopropyl azodicarboxylate (1.66 g, 8.22 mmol, 1.61 mL) and DMF (20.00 mL) was added to a dry 2-dram vial. The mixture was stirred until solids dissolved and then cooled to 0° C. Triphenylphosphine (2.16 g, 8.22 mmol) in DCM (2 ml) was added dropwise to the solution. The reaction mixture was cooled for 30 minutes. The reaction mixture was allowed to warm to room temperature and stirred for 12 hours. Solvent was removed in vacuo and the crude product was purified by reverse phase HPLC to yield the regioisomer [(2R,3S,4S,5R,6R)-6-[(2S,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)tetrahydrofuran-2-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methyl undec-10-ynoate (500.00 mg, 987.09 μmol, 36.03% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | 10 4.10 11-(4-fluorophenyl)undec-9-ynoic acid (18) [32] 4-Fluoroiodobenzene (2.44g, 11.00mmol) was dissolved in dry 46 THF under argon atmosphere (10mL), 77 Pd(PPh3)2Cl2 (0.10g, 0.14mmol, 2.5mol %), 78 CuI (50mg, 0.27mmol, 5mol %), 79 iPr2NH (1.67g, 16.46mmol) and the 80 undec-10-ynoic acid (1.00g, 5.49mmol) were sequentially added. The mixture was stirred at rt for 3h. The mixture was diluted with ethyl acetate and washed with HCl 1N (2×100mL), water, brine, dried over MgSO4 and concentrated under vacuum. The crude was purified by flash chromatography (toluene/ethyl acetate 6:4) to give 1.27g of a pure yellow solid, in 76% of yield. MP: 66-68°C. (0036) 1H NMR (CDCl3, 300MHz) δ 10.2 (br s, 1H), 7.35 (m, 2H), 6.97 (m, 2H), 2.37 (m, 4H), 1.62 (m, 4H), 1.34 (m, 8H). 13C NMR (CDCl3, 75MHz) δ 180.5, 162.1 (d, JCF=246Hz), 133.35 (d, JCF=7.9Hz), 120.2 (d, JCF=2.9Hz), 115.4 (d, JCF=21.8Hz), 90.1, 79.6, 34.2, 29.2, 29.1, 29.0, 28.9, 28.8, 24.7, 19.4. 19F (CDCl3, 282MHz) δ -112, MS (ESI) m/z Calculated for C17H21FO2: 276; Found: 275 [M-1]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With 2-(1H-1,2,3-triazol-1-yl)acetic acid; copper(ll) sulfate pentahydrate; sodium L-ascorbate In water at 20℃; for 20h; | (Synthesis of Exemplified Compound 134) 1H-1,2,3-triazole-1-acetic acid,4,4 ′, 4 ′ ′-[nitrilotris (methylene)] tris-1,1 ′, 1 ′ ′-triethylether (6 mg, 10-undecynoic ether (38 mg, 0.18 mmol)) as an exemplified compound 133 (43 mg, 0.11 mmol) was added to an ethanol solution (3 ml).Then, an aqueous solution (1 ml) of NaAsC (7 mg) and CuSO4.5H2O (4 mg) was added and stirred at room temperature for 20 hours. After evaporating the solvent under reduced pressure, the residue was extracted with ethyl acetate. Water the organic layerThe extract was washed sequentially with brine and dried over sodium sulfate. After filtration and solvent removal, the residue was purified by silica gel column chromatography (CH 2 Cl 2: MeOH = 19: 1) to obtain Exemplified Compound 134 (48 mg, 75%) (yellow oil). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 16h; | |
66% | With dmap; diisopropyl-carbodiimide In dichloromethane Inert atmosphere; Schlenk technique; | |
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Schlenk technique; Inert atmosphere; |
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; | General procedure for the synthesis of NHPI esters General procedure: A round-bottom flask was charged with N-hydroxyphthalimide (NHPI, 815 mg, 5.0 mmol, 1.0 equiv), carboxylic acid (5.0 mmol, 1.0 equiv, if solid), and DMAP (61 mg, 0.5 mmol, 0.1 equiv). Dry dichloromethane (25 mL, 0.2 M) was added, and the mixture was stirred vigorously. Carboxylic acid (1.0 equiv) was added via syringe (if liquid). DIC (780 µL, 5.0 mmol, 1.0 equiv) was added dropwise via syringe, and the mixture was allowed to stir until the carboxylic acid was consumed (determined by TLC). Typical reaction times were between 1 h and 12 h. The mixture was filtered over celite and rinsed with additional CH2Cl2. The solvent was removed under reduced pressure, and purification by column chromatography afforded corresponding activated esters 2 (NHPI esters). All of the NHPI esters have been previously reported. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 24h; Inert atmosphere; | |
93% | Stage #1: undec-10-ynoic acid With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃; for 16h; | 3.1.4. Benzyl undec-10-ynoate (15) To a solution of 10-undecynoic acid (1.0 g, 5.49 mmol), in DMF (4 mL), Cs2CO3 (0.9 g,2.75 mmol) was added and the reaction was stirred at rt for 30 min. Then, benzyl bromide(0.65 mL, 5.49 mmol) was added and the reaction mixture was stirred overnight at rt. Uponcompletion, water was added and the aqueous phase was extracted twice with Et2O. Theorganic layers were combined, dried over Na2SO4, evaporated to dryness and the residuewas then purified by FCC with Hex/EtOAc (95:5) to afford compound 15.Colourless oil [51]; yield: 1.39 g, 93%; 1H-NMR (300 MHz, CDCl3) d 7.37-7.34 (m, 5H),5.12 (s, 2H), 2.35 (t, J = 7.5 Hz, 2H), 2.17 (dt, J = 7.0, 2.6 Hz, 2H), 1.94 (t, J = 2.6 Hz, 1H),1.67-1.62 (m, 2H), 1.54-1.47 (m, 2H), 1.43-1.31 (m, 8H); 13C-NMR (75 MHz, CDCl3) d 173.6,136.1, 128.8 (2C, Aryl), 128.5, 128.3 (2C, Aryl), 84.7, 68.3, 66.2, 34.5, 29.3, 29.2, 29.0, 28.7, 28.6,25.0, 18.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrakis(triphenylphosphine) palladium(0); phenylsilane; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; triethylamine In N,N-dimethyl-formamide at 80℃; for 12h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 70℃; for 18h; Sealed tube; | 1 11-(2-(2,6-dioxopiperidin-3 -yl)-1-oxoisoindolin-4-yl)undec-10-ynoic acid A glass reaction tube was charged with 3-(4-bromo-l -oxoisoindolin-2-yl)piperidine- 2,6-dione (80 mg, 0.24 mmol), undec-10-ynoic acid (45 mg, 0.24 mmol), Cul (5 mg, 0.024 mmol), and PdChlPPloL (17 mg, 0.024 mmol), sealed with a rubber septum and evacuated and filled with N2 three times. Degassed dimethylformamide (2.0 mL) and triethylamine (1.0 mL) were added sequentially, and the reaction mixture was stirred at 70°C for 18 hours. The reaction mixture was purified directly by prep HPLC and appropriate fractions were combined and lyophilized to afford the title as a white solid (40 mg, 0.094 mmol, 38% yield). ESI (in z): [M+H]+ 425.50. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 7h; Inert atmosphere; | Synthesis of compound21 Compound20(110.0 mg, 0.17 mmol, 1.0 equiv) int-BuOH: THF: H2O (v:v:v 1:1:1, 3.0 mL) and 10-undecynoic acid10c(40.8 mg, 0.22 mmol, 1.3 equiv), CuSO45H2O (8.6 mg, 0.034 mmol, 0.2 equiv), NaAsc (13.7 mg, 0.069 mmol, 0.4 equiv) and Tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) (18.3 mg, 0.03 mmol, 0.2 equiv) was added and the reaction mixture was stirred at rt for 7 h. The reaction was stopped, and solvent was dried under vacuum to afford the crude, which was purified by flash chromatography using eluent from DCM to 2% MeOH/DCM to obtain white solid (95 mg, 67%) as the desired product (Rf= 0.5 in 5% MeOH/DCM). m.p. 74.5-77.0 °C.1H NMR (400 MHz, CDCl3)δ7.89-7.79 (m, 4H), 7.71 (d,J= 8.3 Hz, 2H), 7.54-7.47 (m, 2H), 7.38-7.32 (m, 4H), 7.21 (d,J= 7.9 Hz, 2H), 7.11 (s, 1H), 6.20 (d,J= 9.3 Hz, 1H), 5.54-5.48 (m, 1H), 5.34 (t,J= 9.6 Hz, 1H), 4.91 (d,J= 16.5 Hz, 1H), 4.83 (d,J= 16.5 Hz, 1H), 4.74 (d,J= 3.6 Hz, 1H), 4.49-4.41 (m, 1H), 4.22-4.09 (m, 3H), 3.40 (s, 3H), 2.72-2.61 (m, 2H), 2.36 (s, 3H), 2.33 (t,J= 7.4 Hz, 2H), 1.69-1.54 (m, 4H), 1.36-1.29 (m, 8H);13C NMR (100 MHz, CDCl3)δ178.4, 178.1, 166.5, 165.5, 165.0, 149.0, 144.9, 133.5, 132.5, 129.9, 129.8, 128.61, 128.58, 128.5, 128.4, 128.0, 121.9, 97.8, 71.5, 68.7, 68.1, 68.0, 55.8, 52.6, 52.4, 33.91, 33.88, 29.1, 29.01, 28.97, 28.96, 28.93, 28.89, 28.87, 28.6, 28.4, 25.5, 24.71, 24.66, 21.6, 18.4. LC-MS (ESI+) calcd for C41H49N4O12S [M + H]+821.3, found 821.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 16h; Inert atmosphere; | Synthesis of compound8a To a 50 mL RBF,7a(100.0 mg, 0.14 mmol, 1.0 equiv) int-BuOH: THF: H2O (v:v:v 1:1:1, 3.0 mL) and 10-undecynoic acid (33.1 mg, 0.18 mmol, 1.3 equiv), CuSO4·5H2O (7.0 mg, 0.028 mmol, 0.2 equiv) and sodium ascorbate (NaAsc) (11.1 mg, 0.056 mmol, 0.4 equiv) was added sequentially as described and stirred at rt for 16 h. The reaction was monitored after 16 h by1H NMR to see the consumption of starting material and TLC to see no starting material at all. Further purified by flash chromatography using DCM to 2% MeOH/DCM to obtain a white foam (112.0 mg, 89%) as the desired product. (Rf= 0.26 in 5% MeOH/DCM).1H NMR (400 MHz, CDCl3)δ7.88-7.79 (m, 4H), 7.68 (d,J= 8.6 Hz, 2H), 7.56 (d,J= 8.6 Hz, 2H), 7.53-7.44 (m, 3H), 7.38-7.30 (m, 4H), 6.15 (d,J= 9.0 Hz, 1H), 5.52 (t,J= 10.1 Hz, 1H), 5.32 (t,J= 9.8 Hz, 1H), 4.87 (d,J= 3.6 Hz, 1H), 4.60 (s, 2H), 4.53-4.44 (m, 1H), 4.20-4.06 (m, 3H), 4.02-3.94 (m, 1H), 3.92-3.84 (m, 1H), 2.70 (s, 2H), 2.30 (t,J= 7.3 Hz, 2H), 1.86 (s, 3H), 1.68-1.54 (m, 4H), 1.26 (m, 8H);13C NMR (100 MHz, CDCl3)δ177.7, 170.6, 166.8, 165.0, 134.3, 133.6, 133.4, 132.5, 129.8, 129.7, 129.4, 129.2, 128.6, 128.5, 128.40, 128.37, 97.5, 71.1, 68.7, 68.4, 68.3, 66.6, 51.8, 49.6, 33.9, 29.2, 29.0, 28.91, 28.86, 25.5, 24.7, 22.9. HRMS m/z calcd for C41H47BrN4O12SNa [M + Na]+921.1990, found 921.1994. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Inert atmosphere; | Synthesis of compound10d General procedure: 3-azido propionic acid (200.0 mg, 1.74 mmol, 1.0 equiv) and 1,7-octadiyne (276.0 mg, 2.6 mmol, 1.5 equiv) were dissolved int-BuOH: THF: H2O (v:v:v 1:1:1, 25.0 mL), then CuSO4·5H2O (84.8 mg, 0.34 mmol, 0.2 equiv), NaAsc (134.7 mg, 0.68 mmol, 0.4 equiv) were added to the reaction mixture. The reaction was stirred at rt for 24 h, at which time the reaction was completed as indicated by1H NMR and TLC. The reaction was stopped, and solvent was removed using a rotovap, the residue was diluted with EtOAc and acidified using 0.1 N HCl (5.0 mL) followed by water wash. The organic layer was collected and dried over anhydrous Na2SO4and solvent was removed under vacuum to obtain the crude, which was further purified with flash chromatography using eluent of hexanes to 60% EtOAc/Hexanes to obtain the desired product as a yellowish solid (272.0 mg, 71%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 16h; Inert atmosphere; | Synthesis of compound8a To a 50 mL RBF,7a(100.0 mg, 0.14 mmol, 1.0 equiv) int-BuOH: THF: H2O (v:v:v 1:1:1, 3.0 mL) and 10-undecynoic acid (33.1 mg, 0.18 mmol, 1.3 equiv), CuSO4·5H2O (7.0 mg, 0.028 mmol, 0.2 equiv) and sodium ascorbate (NaAsc) (11.1 mg, 0.056 mmol, 0.4 equiv) was added sequentially as described and stirred at rt for 16 h. The reaction was monitored after 16 h by1H NMR to see the consumption of starting material and TLC to see no starting material at all. Further purified by flash chromatography using DCM to 2% MeOH/DCM to obtain a white foam (112.0 mg, 89%) as the desired product. (Rf= 0.26 in 5% MeOH/DCM).1H NMR (400 MHz, CDCl3)δ7.88-7.79 (m, 4H), 7.68 (d,J= 8.6 Hz, 2H), 7.56 (d,J= 8.6 Hz, 2H), 7.53-7.44 (m, 3H), 7.38-7.30 (m, 4H), 6.15 (d,J= 9.0 Hz, 1H), 5.52 (t,J= 10.1 Hz, 1H), 5.32 (t,J= 9.8 Hz, 1H), 4.87 (d,J= 3.6 Hz, 1H), 4.60 (s, 2H), 4.53-4.44 (m, 1H), 4.20-4.06 (m, 3H), 4.02-3.94 (m, 1H), 3.92-3.84 (m, 1H), 2.70 (s, 2H), 2.30 (t,J= 7.3 Hz, 2H), 1.86 (s, 3H), 1.68-1.54 (m, 4H), 1.26 (m, 8H);13C NMR (100 MHz, CDCl3)δ177.7, 170.6, 166.8, 165.0, 134.3, 133.6, 133.4, 132.5, 129.8, 129.7, 129.4, 129.2, 128.6, 128.5, 128.40, 128.37, 97.5, 71.1, 68.7, 68.4, 68.3, 66.6, 51.8, 49.6, 33.9, 29.2, 29.0, 28.91, 28.86, 25.5, 24.7, 22.9. HRMS m/z calcd for C41H47BrN4O12SNa [M + Na]+921.1990, found 921.1994. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 20℃; for 16h; Inert atmosphere; | Synthesis of compound8a To a 50 mL RBF,7a(100.0 mg, 0.14 mmol, 1.0 equiv) int-BuOH: THF: H2O (v:v:v 1:1:1, 3.0 mL) and 10-undecynoic acid (33.1 mg, 0.18 mmol, 1.3 equiv), CuSO4·5H2O (7.0 mg, 0.028 mmol, 0.2 equiv) and sodium ascorbate (NaAsc) (11.1 mg, 0.056 mmol, 0.4 equiv) was added sequentially as described and stirred at rt for 16 h. The reaction was monitored after 16 h by1H NMR to see the consumption of starting material and TLC to see no starting material at all. Further purified by flash chromatography using DCM to 2% MeOH/DCM to obtain a white foam (112.0 mg, 89%) as the desired product. (Rf= 0.26 in 5% MeOH/DCM).1H NMR (400 MHz, CDCl3)δ7.88-7.79 (m, 4H), 7.68 (d,J= 8.6 Hz, 2H), 7.56 (d,J= 8.6 Hz, 2H), 7.53-7.44 (m, 3H), 7.38-7.30 (m, 4H), 6.15 (d,J= 9.0 Hz, 1H), 5.52 (t,J= 10.1 Hz, 1H), 5.32 (t,J= 9.8 Hz, 1H), 4.87 (d,J= 3.6 Hz, 1H), 4.60 (s, 2H), 4.53-4.44 (m, 1H), 4.20-4.06 (m, 3H), 4.02-3.94 (m, 1H), 3.92-3.84 (m, 1H), 2.70 (s, 2H), 2.30 (t,J= 7.3 Hz, 2H), 1.86 (s, 3H), 1.68-1.54 (m, 4H), 1.26 (m, 8H);13C NMR (100 MHz, CDCl3)δ177.7, 170.6, 166.8, 165.0, 134.3, 133.6, 133.4, 132.5, 129.8, 129.7, 129.4, 129.2, 128.6, 128.5, 128.40, 128.37, 97.5, 71.1, 68.7, 68.4, 68.3, 66.6, 51.8, 49.6, 33.9, 29.2, 29.0, 28.91, 28.86, 25.5, 24.7, 22.9. HRMS m/z calcd for C41H47BrN4O12SNa [M + Na]+921.1990, found 921.1994. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With propylamine; hydroxylamine hydrochloride; copper(l) chloride In diethyl ether; water at 0 - 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With copper(l) iodide; hydroxylamine hydrochloride; ethylamine; potassium hydroxide In tetrahydrofuran; methanol; water at 0 - 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With copper(l) iodide; hydroxylamine hydrochloride; ethylamine; potassium hydroxide In tetrahydrofuran; methanol; water at 0 - 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With AuOH(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene); hydrogen fluoride; water In toluene at 50℃; for 18h; Sealed tube; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 30℃; for 16h; Inert atmosphere; | 6 The method of preparation of capsaicin derivatives shown in formula II-4 above, comprising the following steps: In the reaction vessel were added 5-(aminomethyl)-2-methoxyphenol hydrochloride, alkali, 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, alkyne and organic solvents, reacted at 30 °C for 16 hours to obtain the reaction liquid, after the reaction liquid was cooled to room temperature, vacuum concentrated, the residue was obtained after 300 mesh silica gel column chromatography, that is, the capsaicin derivative shown in formula II-4, the yield was 78% of it: Silica gel column chromatography uses a mixture of petroleum ether and ethyl acetate in a volume ratio of 3:1 as the eluent; 5-(Aminomethyl)-2-methoxyphenol hydrochloride or 5-(aminomethyl)-2-methoxybenzene hydrochloride, alkali, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, alkyne acid, organic solvent Molar ratio of 1: 4: 1.5: 1.5: 1: 1: 30. Further, the base is N,N- diisopropylethylamine. Further, the organic solvent is one of acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 50℃; for 12h; Inert atmosphere; | 4 The method for preparing capsaicin derivatives shown in Formula II-2 above, comprising the following steps: In the reaction vessel were added 5-(aminomethyl)-2-methoxybenzene hydrochloride, alkali, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, alkyne and organic solvents, reacted at 50 °C for 12 hours to obtain the reaction liquid, to be cooled to room temperature, vacuum concentrated, the residue over 300 mesh silica gel column chromatography to obtain a white solid, that is, to obtain the capsaicin derivative shown in formula (II), the yield of 72%, wherein: Silica gel column chromatography uses a mixture of petroleum ether and ethyl acetate according to the volume ratio of 5: 1 as the eluent; 5-(Aminomethyl)-2-methoxybenzene hydrochloride, base, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, alkyne acid, organic solvent molar ratio of 1: 4: 1.5: 1.5: 1: 1: 50. Further, the base is N,N- diisopropylethylamine. Further, the organic solvent is acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 18h; |
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 :