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. : | 26825-94-5 | MDL No. : | MFCD00239436 |
Formula : | C11H21BrO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SHCRSWJVWSAMKQ-UHFFFAOYSA-N |
M.W : | 265.19 | Pubchem ID : | 554079 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
90% | With acetyl chloride; for 2h;Heating / reflux; | Step lA solution of 12-bromodecanoic acid or 12-bromododecanoic acid, respectively (30 mmol) in MeOH (50 mL) was added dropwise at 0C to methanolic HCl generated by the addition of <n="73"/>AcCl (8.1 mmol) to MeOH (100 mL). After refluxing for 2 h, the volatiles were removed under reduced pressure. The residue was taken up with EtOAc and washed with saturated aqueous NaHCO3 solution, water, and brine: The organic phase was washed with saturated aqueous NaHCO3 solution and brine, dried (MgSO4), filtered and concentrated under reduced pressure.Methyl 10-bromodecanoate: Pale yellow oil (yield 90 %). 1H NMR (CDCl3, 300 MHz): delta = 1.26-1.35 (m, 10 H, 5 x -CH2-), 1.42 (m, 2 H, -CH2-), 1.62 (m, 2 H, -CH2-), 1.85 (m, 2 H, - CH2-), 2.30 (t, J= 7.5 Hz, -COCH2-), 3.40 (t, J= 6.9 Hz, Br-CH2-), 3.66 (s, 3 H, -OCH3).Methyl 12-bromododecanoate: Pale yellow oil (yield 97 %). 1H NMR (CDCl3, 300 MHz): delta = 1.25-1.35 (m, 12 H, 6 x -CH2-), 1.42 (m, 2 H, -CH2-), 1.62 (m, 2 H, -CH2-), 1.85 (m, 2 H, CH2-), 2.30 (t, J= 7.5 Hz, -COCH2-), 3.40 (t, J= 6.9 Hz, Br-CH2-), 3.66 (s, 3 H, -OCH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium tetrahydroborate In ethanol for 13h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium; lithium diisopropyl amide In tetrahydrofuran; hexane 1) -20 deg C, 10 min, 2) 20 deg C, 2+20 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; ortho-nitrophenyl selenocyanate; dihydrogen peroxide 1) EtOH, THF, 8h, RT 2) 6h, RT; Yield given. Multistep reaction; | ||
Multi-step reaction with 3 steps 1: 1.) aq. NaOH / 1.) 50 deg C 2: 76 percent / tributylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / aq. H2O2 / tetrahydrofuran / 24 h | ||
Multi-step reaction with 3 steps 1: 1.) 20percent KOH / 1.) water, 50 deg C 2: 78 percent / tri-n-butylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h |
Multi-step reaction with 2 steps 1: 76 percent / NaBH4 / ethanol / 13 h / Ambient temperature 2: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With disodium ditelluride In N,N-dimethyl-formamide for 1h; Ambient temperature; | ||
With disodium ditelluride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With pyridine N-oxide; sodium hydrogencarbonate In toluene at 140℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In benzene for 5h; Heating; | |
83% | In N,N-dimethyl-formamide for 14h; Heating; | |
In ethyl acetate for 6h; Heating / reflux; | 53.A A solution of methyl 10-bromodecanoate and triphenyl phosphine in ethyl acetate is heated to reflux for 6 hours. The mixture is cooled and diluted with ether. The resulting precipitate of phosphonium salt is collected by filtration, washed with ether, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With carbon tetrabromide; Cu(tmp)(BINAP)BF<SUB>4</SUB>; sodium bromide In N,N-dimethyl-formamide for 24h; UV-irradiation; Inert atmosphere; | General procedure for the Appel reaction in batch General procedure: To an open oven-dried reaction vial charged with a stir bar was added copper catalyst (2 mg,0.002 mmol, 0.01 equiv), the alcohol (0.20 mmol, 1.0 equiv), carbon tetrabromide (131.6 mg, 0.4mmol, 2.0 equiv) and sodium bromide (41 mg, 0.40 mmol, 2.0 equiv). The flask vial was capped,purged with a stream of nitrogen and dry DMF (1.5 mL) was added via syringe. The reactionmixture was stirred under purple LEDs (394 nm) for 24 h. The vessel was opened and the mixturewas poured into a separatory funnel containing Et2O (10 mL) and H2O (10 mL). The layers wereseparated, and the aqueous layer was extracted with Et2O (2 × 10 mL). The combined organiclayers were washed with sat. Na2S2O3 solution, brine, dried over Na2SO4 and concentrated invacuo. The residue was purified by chromatography (100 % hexanes) |
96% | With phosphorus tribromide Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 63% 2: 34% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In acetonitrile for 16h; Heating / reflux; | 9.2 4-Hydroxy-benzoic acid tert-butyl ester (500 mg, 2.57 mmol) and 10-bromodecanoic acid methyl ester (683 mg, 2.57 mmol) were dissolved in acetonitrile, and K2CO3 (712 mg, 5.15 mmol) was added. The mixture was refluxed under nitrogen for 16 h, and cooled to rt.The solids were filtered off, and the filtrate concentrated under vacuum. The resulting residue was dissolved in AcOEt (50 ml) and water (25 ml_). The phases were separated and the organic phase was dried over MgSO4 and concentrated to yield a colorless oil (874 mg, 90% yield). HPLC-MS m/z: 402 (M+23).1H-NMR (CDCI3, 400 MHz) 7.92 (d, 2H), 6.87 (d, 2H), 3.99 (t, 2H), 3.67 (s, 3H), 2.31(t, 2H), 1.72-1.83 (m, 2H), 1.59-1.69 (m, 2H), 1.58 (s, 9H), 1.40-1.50 (m, 2H), 1.23-1.40 (br,8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 1.) aq. NaOH / 1.) 50 deg C 2: 76 percent / tributylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / aq. H2O2 / tetrahydrofuran / 24 h 5: aq. KOH / 0.5 h / Heating | ||
Multi-step reaction with 5 steps 1: 1.) 20percent KOH / 1.) water, 50 deg C 2: 78 percent / tri-n-butylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h 5: 30percent KOH / ethanol / 0.5 h / Heating | ||
Multi-step reaction with 4 steps 1: 76 percent / NaBH4 / ethanol / 13 h / Ambient temperature 2: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h 4: 30percent KOH / ethanol / 0.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 1.) aq. NaOH / 1.) 50 deg C 2: 76 percent / tributylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / aq. H2O2 / tetrahydrofuran / 24 h | ||
Multi-step reaction with 4 steps 1: 1.) 20percent KOH / 1.) water, 50 deg C 2: 78 percent / tri-n-butylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature 3: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h | ||
Multi-step reaction with 3 steps 1: 76 percent / NaBH4 / ethanol / 13 h / Ambient temperature 2: 84 percent / 30percent H2O2 / tetrahydrofuran / 15 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) aq. NaOH / 1.) 50 deg C 2: 76 percent / tributylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: 1.) 20percent KOH / 1.) water, 50 deg C 2: 78 percent / tri-n-butylphosphine / tetrahydrofuran / 0.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: Na2Te2 2: NaBH4 4: 1 N sodium hydroxide / ethanol / Heating | ||
Multi-step reaction with 4 steps 1: Na2Te2 / dimethylformamide / 1 h / Ambient temperature 2: NaBH4 / ethanol 3: ethanol / 1 h / Ambient temperature 4: 38 percent / 1N aq. NaOH / ethanol / 0.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: Na2Te2 2: NaBH4 | ||
Multi-step reaction with 3 steps 1: Na2Te2 / dimethylformamide / 1 h / Ambient temperature 2: NaBH4 / ethanol 3: ethanol / 1 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: Na2Te2 2: NaBH4 | ||
Multi-step reaction with 2 steps 1: Na2Te2 / dimethylformamide / 1 h / Ambient temperature 2: NaBH4 / ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 1) o-Nitrophenyl selenocyanate, NaBH4 2) 30percent H2O2 / 1) EtOH, THF, 8h, RT 2) 6h, RT 2: 90 percent / KOH / H2O; tetrahydrofuran / 14 h / Ambient temperature 3: 90 percent / methyltrioctylammonium chloride, 48percent HBr / 0.75 h / 110 °C 4: 95 percent / NaN3, tetrabutylammonium bromide / H2O / 16 h / 80 °C 5: 99 percent / H2 / 5percent Pd/C / methanol / 1 h / 760 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 1) o-Nitrophenyl selenocyanate, NaBH4 2) 30percent H2O2 / 1) EtOH, THF, 8h, RT 2) 6h, RT 2: 90 percent / KOH / H2O; tetrahydrofuran / 14 h / Ambient temperature 3: 90 percent / methyltrioctylammonium chloride, 48percent HBr / 0.75 h / 110 °C 4: 95 percent / NaN3, tetrabutylammonium bromide / H2O / 16 h / 80 °C 5: 60 percent / DCC / CH2Cl2 / 2 h / 0 °C 6: 45 percent / benzeneselenol, Et3N, SnCl2 / acetonitrile / 6 h | ||
Multi-step reaction with 6 steps 1: 1) o-Nitrophenyl selenocyanate, NaBH4 2) 30percent H2O2 / 1) EtOH, THF, 8h, RT 2) 6h, RT 2: 90 percent / KOH / H2O; tetrahydrofuran / 14 h / Ambient temperature 3: 90 percent / methyltrioctylammonium chloride, 48percent HBr / 0.75 h / 110 °C 4: 95 percent / NaN3, tetrabutylammonium bromide / H2O / 16 h / 80 °C 5: 90 percent / triethylamine / toluene; CH2Cl2 / 1 h / 0 °C 6: 45 percent / benzeneselenol, SnCl2, DMAP / acetonitrile / 6 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 1) o-Nitrophenyl selenocyanate, NaBH4 2) 30percent H2O2 / 1) EtOH, THF, 8h, RT 2) 6h, RT 2: 90 percent / KOH / H2O; tetrahydrofuran / 14 h / Ambient temperature 3: 90 percent / methyltrioctylammonium chloride, 48percent HBr / 0.75 h / 110 °C 4: 95 percent / NaN3, tetrabutylammonium bromide / H2O / 16 h / 80 °C 5: 60 percent / DCC / CH2Cl2 / 2 h / 0 °C 6: 25 percent / benzeneselenol, Et3N, SnCl2 / acetonitrile / 6 h | ||
Multi-step reaction with 6 steps 1: 1) o-Nitrophenyl selenocyanate, NaBH4 2) 30percent H2O2 / 1) EtOH, THF, 8h, RT 2) 6h, RT 2: 90 percent / KOH / H2O; tetrahydrofuran / 14 h / Ambient temperature 3: 90 percent / methyltrioctylammonium chloride, 48percent HBr / 0.75 h / 110 °C 4: 95 percent / NaN3, tetrabutylammonium bromide / H2O / 16 h / 80 °C 5: 90 percent / triethylamine / toluene; CH2Cl2 / 1 h / 0 °C 6: 25 percent / benzeneselenol, SnCl2, DMAP / acetonitrile / 6 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, RT, 20 min, 2.) DMF, RT, 2 h 2: 5 N aq. NaOH / methanol / 0.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, RT, 20 min, 2.) DMF, RT, 2 h 2: 5 N aq. NaOH / methanol / 0.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 100 deg C, 0.5 h, 2.) DMF, RT, 2 h 2: 5 N aq. NaOH / methanol / 0.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; | EXAMPLE 2 Methyl-10-bromodecanoate A solution of <strong>[50530-12-6]10-bromodecanoic acid</strong> (5 g) in methanol (60 ml) and concentrated sulphuric acid (3 drops) was refluxed for 20 hours. The methanol was evaporated in vacuo, and the residual oil partitioned between water (50 ml) and dichloromethane (2*50 ml). The organic extracts were washed with 10% sodium carbonate (2*100 ml) and saturated brine (2*100 ml), and dried over magnesium sulphate and evaporated in vacuo to give the required product as a nearly colourless oil. | |
In methanol; | EXAMPLE 2 Methyl-10-bromodecanoate A solution of <strong>[50530-12-6]10-bromodecanoic acid</strong> (5 g) in methanol (60 ml) and concentrated sulphuric acid (3 drops) was refluxed for 20 hours. The methanol was evaporated in vacuo , and the residual oil partitioned between water (50 ml) and dichloromethane (2 x 50 ml). The organic extracts were washed with 10% sodium carbonate (2 x 100 ml) and saturated brine (2 x 100 ml), and dried over magnesium sulphate and evaporated in vacuo to give the required product as a nearly colourless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 50℃; for 48h; | 4-Nitro-3-trifluoromethylaniline (lOOmg) was dissolved in 5mL DMF with stirring. To this was added 10-bromodecanoic acid methyl ester (leq., 128mg) followed by potassium carbonate (2eq., 134mg). After stirring at room temperature and seeing no change by TLC (50% ethyl acetate / hexanes), the reaction mixture was heated to 5O0C.After another 2 days, the reaction was judged complete by TLC, and the mixture was allowed to cool to room temperature, HClaq added and extracted into ethyl acetate (EA).The organic layer was washed with water then concentrated. Chromatography (silica, 25% EA / hexanes). Trituration of the recovered material afforded 72mg (38%). 1HNMR (500MHz, CDCl3) delta 8.03 (d, J = 9.0 Hz, IH); 6.87 (d, J = 2.6 Hz, IH); 6.64 (dd,J = 9.0, 2.6 Hz, IH); 4.58 (t, J = 5.2 Hz, IH); 3.67 (s, 3H); 3.21 (td, J = 7.1, 5.2 Hz,2H); 2.31 (t, J = 7.5 Hz, 2H); 1.70-1.59 (m, 4H); 1.46-1.29 (m, 10H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With N-ethyl-N,N-diisopropylamine; potassium iodide In N,N-dimethyl-formamide at 60℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: methanesulfonamide With sodium hydride In N,N-dimethyl-formamide at 100℃; for 2h; Stage #2: 10-bromodecanoic acid methyl ester In N,N-dimethyl-formamide at 100℃; | 2 Methyl 10-(methylsulfonamido)decanoate: In a Schlenk flask flushed with argon, methanesulfonamide (0.94 g, 9.9 mmol) was added to a suspension of NaH (0.45 g of a 60 % dispersion in mineral oil, 11.3 mmol) in dry DMF (5 mL). After stirring for 2 h at 100°C was added a solution of methyl 10-bromodecanoate (2.5 g, 9.4 mmol) in dry DMF (5 mL) and the mixture was stirred at 100°C overnight. The solvent was removed under reduced pressure, and to the residue was added water. After acidification with diluted HCl, the product was extracted with dichloromethane. The organic phase was dried (MgSO4) and concentrated to yield a yellow oil (2.61 g, 99 %) which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With sodium hydride In hexane; N,N-dimethyl-formamide for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | at 120℃; for 2h; | |
at 120℃; for 2h; | 3-(9-methoxycarbonylnonyl)-1,1,2-trimethyl-1H-benzo[e]indolenium bromide (2j) 1,1,2-Trimethylbenzo[e]indole (947 mg, 4.52 mmol) and 10-bromodecanoic acid methyl ester (400 mg, 1.50 mmol) were reacted and worked up analogously to 3-(4-methoxycarbonylbutyl)-1,1,2-trimethyl-1H-benzo[e]indolenium bromide (2i). Yield: 310 mg (18% content, 40% in addition to starting material according to 1H NMR spectroscopy) grayish solid. 1H NMR (200 MHz, CDCl3): δ=8.14-8.00 (m, 4H, CHaromatic), 7.79-7.60 (m, 2H, CHaromatic), 4.86 (t, 2H, NCH2, 3J=7.7 Hz), 3.64 (s, 3H, OCH3), 3.22 (s, 3H, CH3), 2.27 (t, 2H, 3J=7.3 Hz), 2.08-1.90 (m, 4H, 2×CH2), 1.88 (s, 6H, 2×CH3), 1.60-1.30 ppm (m, 10H, 5×CH2), HRMS (ESI) (C26H36NO2+): calculated 394.2741, found 394.2729, Δ=-1.2 mmu. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; potassium iodide In acetone for 24h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 10-bromodecanoic acid methyl ester With thiourea In ethanol for 18h; Reflux; Stage #2: With water; sodium hydroxide for 1h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate In acetonitrile for 18h; Inert atmosphere; Reflux; | 20 Preparation of 3-(9-Carboxy-nonyloxy)benzoic acid tert-butyl ester 3-Hydroxy-benzoic acid tert-butyl ester (3 g) was dissolved in acetonitrile (50 mL). 10-Bromo decanoic acid methyl ester from Aldrich (4.1 g) in acetonitrile (20 mL) was added and washing the vessel with acetonitrile (30 mL). Potassium carbonate was added and the mixture was refluxed under nitrogen for ca. 18 h. The reaction was cooled and evaporated to dryness. The residue was dissolved in AcOEt (80 mL) and water (30 mL) and extracted. The aqueous phase was washed with AcOEt (30 mL) and the combined organic phases were washed with water (50 mL), sat. NaCl (30 mL) and dried over MgSO4 and the filtrate was concentrated under vacuum to yield a white solid (5.8 g). The residue was dissolved in DCM (15 mL) and heptane (ca 60 mL) was added, and the solution was concentrated to ca. 30 mL. After stirring for 30 min. crystals began to form, and the solution was ice-cooled. The crystals were filtered off and washed with cooled heptane and dried in under vacuum to yield 4.13 g (71%) of 3-(9-methoxycarbonyl-nonyloxy)-benzoic acid tert-butyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.7% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.25h; Inert atmosphere; | 4 N3-decanoicacid-methylester-2'-deoxythymidine 18 N3-decanoicacid-methylester-2'-deoxythymidine 18 2'-deoxythymidine (500 mg, 2.06 mmol) and the bromodecanoicacid methyl ester 14 (800 mg, 3.09 mmol, 1.5 eq.) were dissolved in anhydrous DMF (5 ml) and cooled to 0° C. NaH (50-60% in oil, 148.6 mg, 3.09 mmol, 1.5 eq.) was slowly added. The suspension was stirred under N2 and at 0° C. for 15 min, then allowed to warm to rt. The reaction was quenched after 16 h by the addition of sat. brine. The aqueous phase was extracted with EtOAc (3*) and the organic phase was then dried over MgSO4, filtered, and concentrated. Purification by FC (silica gel, pure CH2Cl2 to 93:7 CH2Cl2/MeOH) yielded the title compound 18 (colourless oil, 358.1 mg, 0.84 mmol, 40.7%) as the major product. TLC (silica gel, 97:3 CH2Cl2/MeOH): Rf 0.21. LR-ESI+-TOF-MS (methanol): calc. for C21H34O7N2Na: 449.49. found: 449.0. 1H-NMR (400 MHz, DMSO-d6, δ(ppm)): 7.75 (s, 1H, H-C(6)), 6.20 (t, 1H, J=6.6, H-C(1')), 5.21 (d, br, 1H, J=4.0, OH-C(3')), 5.01 (t, br, 1H, J=4.8, OH-C(5')), 4.24 (m, 1H, H-C(3')), 3.76 (m, 2H, -CH2), 3.58 (m, 2H, H-C(5')), 3.56 (s, 3H, -OCH3), 2.26 (t, 2H, J=7.0, -CH2), 2.01 (t, 2H, J=5.8, H-C(2')), 1.81 (s, 3H, -C(5)-CH3), 1.48 (d, 4H, J=6.8, 2* -CH2), 1.23 (s, 10H, 5* -CH2). 13C-NMR (101 MHz, DMSO-d6, δ (ppm)): 173.1, 162.4, 150.2, 134.5, 108.3, 87.2, 84.6, 70.1, 61.1, 50.9, 33.1, 28.4, 26.8, 26.1, 24.2, 12.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chloro-trimethyl-silane; ethylene dibromide; lithium chloride Inert atmosphere; Reflux; | 4.4 General procedure (C) for the preparation of organozinc halides through oxidative addition to alkyl bromides General procedure: In a 2-neck round-bottom flask equipped with a reflux condenser, under inert atmosphere, one equiv. of LiCl was added. The system was warmed up to 150-170°C, at reduced pressure (0.1mbar), for 20min. Two equiv. of zinc powder were added, and the system was again warmed up to 150-170°C, at reduced pressure (0.1mbar), for 20min. The flask was let cooling down to room temperature and treated with 3 cycles of vacuum-argon. Afterwards dry THF (1mL/mmol of corresponding alkyl bromide) and 10mol% of 1,2-dibromoethane were added. The mixture was let stirring at 65°C for 15min and cooled down at room temperature. Depending on substrate, 1 or 5mol% of trimethylsilyl chloride were added, and the solution was warmed up to 65°C for 15min and then cooled down to room temperature. The suitable alkyl bromide (1 equiv.) was then added dropwise and the solution stirred at reflux for 3h. The solution was cooled down to room temperature and 10mol% of 1,2-dibromoethane were added. The solution was again warmed up to reflux and the reaction was followed by GC, until complete conversion. Once the reaction went to completion, the flask was let cooling down at room temperature and zinc was let precipitating over 6h. The titration of organozinc compound was carried out by iodometry, using a literature method. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: ethyl acetate / 6 h / Heating / reflux 2: sodium hydride; dimethyl sulfoxide / 3 h / 20 °C 3: dimethyl sulfoxide / 18 h / 20 °C 4: hydrogen / palladium 10% on activated carbon / ethanol / 3102.97 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: ethyl acetate / 6 h / Heating / reflux 2: sodium hydride; dimethyl sulfoxide / 3 h / 20 °C 3: dimethyl sulfoxide / 18 h / 20 °C 4: hydrogen / palladium 10% on activated carbon / ethanol / 3102.97 Torr 5: potassium hydroxide / ethanol / 24 h / Heating / reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: ethyl acetate / 6 h / Heating / reflux 2: sodium hydride; dimethyl sulfoxide / 3 h / 20 °C 3: dimethyl sulfoxide / 18 h / 20 °C 4: hydrogen / palladium 10% on activated carbon / ethanol / 3102.97 Torr 5: potassium hydroxide / ethanol / 24 h / Heating / reflux 6: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: ethyl acetate / 6 h / Heating / reflux 2: sodium hydride; dimethyl sulfoxide / 3 h / 20 °C 3: dimethyl sulfoxide / 18 h / 20 °C 4: hydrogen / palladium 10% on activated carbon / ethanol / 3102.97 Torr 5: potassium hydroxide / ethanol / 24 h / Heating / reflux 6: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: ethyl acetate / 6 h / Heating / reflux 2: sodium hydride; dimethyl sulfoxide / 3 h / 20 °C 3: dimethyl sulfoxide / 18 h / 20 °C 4: hydrogen / palladium 10% on activated carbon / ethanol / 3102.97 Torr 5: potassium hydroxide / ethanol / 24 h / Heating / reflux 6: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 20 °C 7: 2,4,6-trimethyl-pyridine; 1-hydroxy-7-aza-benzotriazole; diisopropyl-carbodiimide / dimethyl sulfoxide / 24 h / 20 °C 8: piperidine / N,N-dimethyl-formamide / 0.17 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium carbonate In acetonitrile at 70℃; for 18h; | Intermediate 11a: Methyl 10-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)decanoate Intermediate 11a: Methyl 10-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)decanoate Methyl 10-bromodecanoate (82 mg, 0.31 mmol) was added in one portion to 3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenol (120 mg, 0.31 mmol) and potassium carbonate (64.0 mg, 0.46 mmol) in MeCN (2 mL) at 20° C. The resulting suspension was stirred at 70° C. for 18 hours. The mixture was cooled to RT and was diluted with DCM (10 mL) and water (2 mL). The DCM layer was collected and evaporated to afford crude material as a yellow gum. The crude product was purified by flash column chromatography, elution gradient 0 to 30% EtOAc in heptane to afford the title compound (134 mg, 76%) as a colourless gum; 1H NMR (400 MHz, DMSO-d6) 1.05 (3H, d), 1.09-1.23 (6H, m), 1.23-1.33 (8H, m), 1.35-1.44 (2H, m), 1.46-1.59 (2H, m), 1.69 (2H, p), 2.29 (2H, t), 2.34-2.42 (1H, m), 2.55-2.6 (1H, m), 2.78-2.96 (2H, m), 3.48-3.55 (1H, m), 3.58 (3H, s), 3.97 (2H, t), 5.13 (1H, s), 6.64 (2H, d), 6.97 (2H, m), 7.18 (1H, d), 7.39 (1H, d), 10.49 (1H, s); m/z: ES+ [M+H]+ 573.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: N-demethyltamoxifen With sodium hydride In N,N-dimethyl-formamide for 0.25h; Cooling with ice; Inert atmosphere; Stage #2: 10-bromodecanoic acid methyl ester In N,N-dimethyl-formamide for 24h; Inert atmosphere; Cooling with ice; | Methyl 5-(N-desmethyltamoxifen-N-yl) pentanoate (1) General procedure: Sodium hydride (80 mg, 3.3 mmol) was added to a solution of N-desmethyltamoxifen (433 mg, 1.21 mmol) in dry DMF (20 mL) under ice-water cooling. After stirring for 15 min., methyl 5-bromovalerate (0.26 mL, 1.8 mmol) was added dropwise. After 30 min., the cooling bath was removed and stirring was continued for 24 h. Water (100 mL) was added and the mixture was extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with water, dried over sodium sulfate, and the solvent was evaporated under vacuum. The residue was subjected to column chromatography using ethyl acetate - methanol (10:2) to yield compound 1 (292 mg, 51 %) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 10-bromodecanoic acid methyl ester; 3-(((5-chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-2,5-difluorophenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; Inert atmosphere; Stage #2: With lithium hydroxide at 50℃; for 16h; Inert atmosphere; | 10-(3-(((5-Chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-2,5-difluorophenoxy)decanoic acid Methyl 10-bromodecanoate (347 mg, 1.309 mmol) was added to a stirred mixture of 3-(((5-chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-2,5-difluorophenol (400 mg, 1.091mmol) and potassium carbonate (301 mg, 2.181 mmol) in DMF (3.34 mL). The reaction mixture washeated to 80 °C for 3.5 h under a nitrogen atmosphere. The reaction mixture was cooled to roomtemperature and diluted with water (10 mL) and extracted with DCM (2 x 10 mL). The organic layerswere combined, passed through a hydrophobic frit and the solvent was concentrated in vacuo. Thereaction mixture was added LiOH (261 mg, 10.91 mmol) and heated to 50 °C for 16 h under a nitrogenatmosphere. The reaction mixture was filtered hot and the solvent was removed in vacuo to afford10-(3-(((5-chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)methyl)-2,5-difluorophenoxy)decanoic acid (352 mg, 0.655 mmol, 60 % yield) as a white solid. M.pt.: 105 - 107 °C; νmax(neat): 3440, 2913, 2851, 1637, 1551, 1489 cm1; 1H NMR (400 MHz, DMSO-d6) δ = 9.04 (1H, br s), 7.93(1H, s), 7.67 (1H, br s), 7.51 (1H, br s), 7.29 (1H, br s), 6.98 (1H, ddd, J = 10.1, 6.8, 2.9 Hz), 6.50 - 6.60 (1H, m), 4.65 (2H, br d, J = 5.9 Hz), 4.04 (2H, t, J = 6.5 Hz), 3.70 (3H, s), 2.19 (2 H, t, J = 7.3 Hz), 1.65 -1.77 (2H, m), 1.49 (2H, m), 1.25 - 1.42 (11 H, m); 13C NMR (101 MHz, DMSO-d6) δ = 175.0, 159.7, 158.1,158.0, 157.3, 148.0, 147.8, 129.9, 129.0, 128.9, 128.9, 128.8, 123.9, 101.6, 101.4, 69.6, 38.8, 34.2,29.3, 29.1, 29.1, 29.0, 28.9, 25.8, 25.0; 19F NMR (376 MHz, DMSO-d6) δ = -116.2 (s), -145.9 (s); LCMS(Method A): tR = 1.02 min, [M+H]+ 537 & 539 (99 % purity); HRMS: (C25H32ClF2N6O3) [M+H]+ requires537.2192, found [M+H]+ 537.2196. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 10-bromodecanoic acid methyl ester; 4-(2,6-difluoro-4-(3-(3-methoxy-4-(3-(piperazin-1-yl)propoxy)phenyl)quinoxalin-5-yl)benzyl)thiomorpholine 1,1-dioxide With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16h; Inert atmosphere; Stage #2: With lithium hydroxide at 50℃; for 3h; Inert atmosphere; | (2S,4S)-1-((S)-2-Cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-4-(10-(4-(3-(4-(8-(4-((1,1-dioxidothiomorpholino)methyl)-3,5-difluorophenyl)quinoxalin-2-yl)-2-methoxyphenoxy)propyl)-piperazin-1-yl)decanamido)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxamide (JP-6) 4-(2,6-Difluoro-4-(3-(3-methoxy-4-(3-(piperazin-1-yl)propoxy)phenyl)quinoxalin-5-yl)benzyl)thiomorpholine1,1-dioxide (400 mg, 0.627 mmol) was added to a stirred mixture of methyl 10-bromodecanoate (200 mg, 0.753 mmol) and potassium carbonate (173 mg, 1.254 mmol) in DMF (1.92mL). The reaction mixture was heated to 100 °C for 16 h under a nitrogen atmosphere. The reactionmixture was cooled to room temperature and diluted with water (10 mL) and extracted with DCM (3x 10 mL). The organic layers were combined, passed through a hydrophobic frit and the solvent wasconcentrated in vacuo. LiOH (150 mg, 6.27 mmol) was added and the reaction mixture was heated at50 °C for 3 h under a nitrogen atmosphere. The reaction mixture was filtered and purified by reversephase prep column chromatography (30 - 95 % MeCN + 0.1 % HCO2H in H2O + 0.1 % HCO2H, SunFireC18, 42 mL/ min, 45 min) to afford 10-(4-(3-(4-(8-(4-((1,1-dioxidothiomorpholino)methyl)-3,5-difluorophenyl)quinoxalin-2-yl)-2-methoxyphenoxy)propyl)piperazin-1-yl)decanoic acid (354 mg,0.438 mmol, 70 % yield) as a yellow solid. 10-(4-(3-(4-(8-(4-((1,1-Dioxidothiomorpholino)methyl)-3,5-difluorophenyl)quinoxalin-2-yl)-2-methoxyphenoxy)propyl)piperazin-1-yl)decanoic acid (100 mg,0.124 mmol), tert-butyl ((S)-1-(((S)-2-((2S,4S)-4-amino-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-1-yl)-1-cyclohexyl-2-oxoethyl)amino)-1-oxopropan-2-yl)(methyl)carbamate(87 mg, 0.149 mmol), triethylamine (51.8 μL, 0.371 mmol) and HATU (70.6 mg, 0.186 mmol) werestirred together in DMF (2.475 mL) for 15 h at room temperature. The reaction mixture was dilutedwith water (10 mL) and extracted with DCM (3 x 10 mL). The solvent was concentrated in vacuo andTFA (95 μL, 1.238 mmol) was added and the reaction mixture was stirred at room temperature for 16h. The reaction mixture was diluted with water (10 mL) and extracted with DCM (3 x 10 mL). Thesolvent was concentrated in vacuo and purified by reverse phase prep column chromatography (70 -95 % MeCN in H2O + 0.1 % NH4HCO3, XBridge C18, 42 mL/min, 45 min) to afford (2S,4S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-4-(10-(4-(3-(4-(8-(4-((1,1-dioxidothiomorpholino)methyl)-3,5-difluorophenyl)quinoxalin-2-yl)-2-methoxyphenoxy)propyl)piperazin-1-yl)decanamido)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxamide (JP-6) (85 mg,0.067 mmol, 54 % yield) as a yellow solid. M.pt.: 100 - 102 °C; νmax (neat): 3315, 2928, 2853, 1632,1469, 1126 cm1; 1H NMR (400 MHz, CDCl3) δ = 9.38 (1H, s), 8.14 (1H, dd, J = 8.2, 1.6 Hz), 7.88 - 8.00(1H, m), 7.85 (1H, d, J = 1.5 Hz), 7.85 (1H, dd, J = 18.2, 1.8 Hz), 7.79 - 7.81 (1H, m), 7.75 - 7.79 (1H, m),7.70 (1H, dd, J = 8.4, 2.1 Hz), 7.49 (2H, d, J = 9.0 Hz), 7.11 - 7.16 (2H, m), 7.05 - 7.09 (2H, m), 7.02 (1H,d, J = 8.3 Hz), 5.08 - 5.16 (1H, m), 4.74 (1H, d, J = 8.8 Hz), 4.59 (1H, q, J = 6.1 Hz), 4.36 (1H, t, J = 8.2 Hz),4.17 (2H, t, J = 6.7 Hz), 4.07 (1H, dd, J = 11.2, 5.1 Hz), 3.95 (3H, s), 3.93 (2H, s), 3.68 (1H, d, J = 10.8 Hz),3.07 - 3.16 (8H, m), 3.00 - 3.04 (1H, m), 2.70 - 2.85 (2H, m), 2.47 - 2.63 (9H, m), 2.30 - 2.43 (7H, m),1.99 - 2.24 (8H, m), 1.78 - 1.90 (4H, m), 1.67 - 1.73 (2H, m), 1.36 - 1.63 (7H, m), 1.25 - 1.35 (12H, m),1.23 (1H, d, J = 6.8 Hz), 1.09 (3H, br s), 0.88 - 1.05 (2H, m); 13C NMR (101 MHz, CDCl3) δ = 175.0, 173.3,173.1, 171.2, 161.3 (2C, dd, J = 246.5, 9.5 Hz), 150.9, 150.5, 150.2, 142.7, 141.4, 140.7 (t, J = 11.0 Hz),139.4, 137.3, 137.3, 136.1, 130.5, 129.9, 129.2, 129.1, 128.8, 128.2, 127.3, 126.0, 120.1, 114.0 (2C, dd, J = 19.8, 5.9 Hz), 112.7, 110.8 (t, J = 20.2 Hz), 110.4, 67.5, 60.2, 60.1, 60.1, 60.0, 58.8, 55.9, 55.7, 55.0,54.7, 53.2 (2C), 53.1 (2C), 51.5 (2C), 50.1 (2C), 49.4, 48.0, 40.6, 36.9, 35.1, 31.1, 30.0, 29.6, 29.4, 29.3,29.2, 29.1, 28.6, 27.6, 26.8, 26.6, 26.1, 26.0, 25.9, 25.7, 20.1, 19.4; 19F NMR (376 MHz, CDCl3) δ = -115.18 (s); LCMS (Method B): tR = 1.62 min, [(M+2H)/2]+ 637 (100 % purity); HRMS: (C70H94F2N10O8S)[M+H]+ requires 1273.7023, found [M+H]+ 1273.7014. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 1.5h; Sealed tube; | Methyl 10-(4-nitro-1H-pyrazol-1-yl)decanoate 4-Nitro-1H-pyrazole (1 g, 8.84 mmol), methyl 10-bromodecanoate (3.09 mL, 13.27 mmol) andpotassium carbonate (1.833 g, 13.27 mmol) were sealed within a vessel and DMF (10 mL) was added.The reaction mixture was heated at 50 °C for 1.5 h. The reaction mixture was diluted with water (30mL) and extracted with DCM (3 x 30 mL). The organic layers were combined, passed through ahydrophobic frit and the solvent was removed in vacuo. The residue was purified by normal phasecolumn chromatography (0 - 100 % EtOAc in cyclohexane, 80 g SiO2) to afford methyl 10-(4-nitro-1Hpyrazol-1-yl)decanoate (2.2 g, 7.40 mmol, 84 % yield) as a white solid. M.pt.: 69 - 71 °C; νmax (neat):3151, 3123, 2928, 2855, 1722, 1533 cm1; 1H NMR (400 MHz, DMSO-d6) δ = 8.89 (1H, s), 8.24 (1H, s),4.16 (2H, t, J = 7.1 Hz), 3.58 (3H, s), 2.27 (2H, t, J = 7.3 Hz), 1.80 (2H, quin, J = 7.0 Hz), 1.45 - 1.54 (2H,m), 1.23 (10H, br s); 13C NMR (101 MHz, DMSO-d6) δ = 173.8, 135.9, 135.2, 130.8, 52.8, 51.6, 33.7, 3729.5, 29.1, 29.0, 28.9, 28.7, 26.1, 24.9; LCMS (Method A): tR = 1.28 min, [M+H]+ 298, (100 % purity);HRMS: (C14H24N3O4) [M+H]+ requires 298.1767, found [M+H]+ 298.1767. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: tert-butyl (R)-4-(4-chlorophenyl)-5-((4-(4-(((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-3,6-dihydropyridine-1(2H)-carboxylate With trifluoroacetic acid In dichloromethane at 0℃; for 1h; Stage #2: 10-bromodecanoic acid methyl ester With triethylamine In ethanol at 100℃; Microwave irradiation; | 49 Preparation of methyl (R)-10-(4-(4-chlorophenyl)-5-((4-(4-(((4-((4- morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1- yl)methyl)-3,6-dihydropyridin-1(2H)-yl)decanoate (14.0): TFA (0.5 mL) was added to a solution of compound 12.6 (50 mg, 0.053 mmol) in DCM (1 mL). After stirring at 0 °C for 1 h, the resulting mixture was condensed to afford a residue which was mixed with TEA (44 pL, 0.318 mmol) and bromo ester (44 mg, 0.159 mmol) in ethanol (3 mL). The resulting mixture was stirred under microwave radiation at 100 °C for 2-4 h. Removal of the solvent under reduced pressure afforded a residue which was chromatographed on silica gel to yield the title compound (36 mg, 61% yield). 1H NMR (600 MHz, CDC ) d 8.36 (s, 1 H), 8.06 (d, J = 8.7 Hz, 1 H), 7.87 (d, J = 8.6 Hz, 2H), 7.37 (d, J = 7.4 Hz, 2H), 7.34 - 7.27 (m, 4H), 7.24 (t, J = 7.2 Hz, 1 H), 7.07 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 7.5 Hz, 1 H), 6.75 (d, J = 8.5 Hz, 2H), 6.56 (d, J = 9.3 Hz, 1 H), 3.87 (s, 1 H), 3.73 - 3.65 (m, 5H), 3.65 (s, 3H), 3.31 - 3.20 (m, 5H), 3.18 - 3.06 (m, 4H), 3.04 - 2.95 (m, 3H), 2.67 - 2.33 (m, 10H), 2.27 (t, J = 7.5 Hz, 2H), 2.19 - 2.1 1 (m, 1 H), 1.98 - 1.88 (m, 2H), 1.75 - 1.65 (m, 1 H), 1.64 - 1.53 (m, 2H), 1.38 - 1.18 (m, 14H). ESI+, m/z [M+H]+ = 1 131.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 70℃; for 15h; Inert atmosphere; | 1.1 Method 1: General procedure: To a solution of suitably substituted purine (2 mmol) and RBr/RC1/RI (2.5 mmol) in anhyd. DMF (5 mL) anhyd. potassium carbonate (3 mmol) and a few crystals of NaT were added. The suspension was slowly heated in an oil-bath at 65-70°C for 3 h under argon. Progress of the reaction was monitored on TLC using DCM-MeOH (2.5%). After the completion of the reaction,the reaction mixture was cooled to rt and concentrated at 50 °C to remove most of DMF. Hexane (10 mL) was added and remaining DMF was removed. The residue was partitioned between EtOAc (50 mL) and water (15 mL). Organic layer was separated,and aq. layer was re-extracted in EtOAc (25 mL). Combined organic layer was washed with water (15m1),sodium bicarbonate (5%,2X 15 mL) and later with satd. NaC1 solution (10 mL). Organic layer was dried over anhyd. Na2SO4,filtered and concentrated. Residue was mixed with silica gel and purified by CombiFlash using hexanes and EtOAc as eluent. Fractions with same Rf values were collected and appropriate tubes were mixed,concentrated,to give the both regiomers A and B which were confirmed by ‘H-NIVIR andLCMS.Step 1: Utilized similar method as described in method 1 from 8-Methylxanthine (2.8 g,15.55 mmol). The crude solid was filtered and dried under high vacuum to give the desired product (4.66 g,82%) as a white solid. ‘H-NMR (CDC13 with 0.03% v/v TMS) ö 8.26 (bs,1H),4.20 (t,J = 7.4 Hz,2H),3.67(s,3H),3.52 (s,3H),2.47 (s,3H),2.30 (t,J = 7.4 Hz,2H),1.78 (m,2H),1.60 (m,2H),1.4-1.2 (m,1OH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With manganese; (1,2-dimethoxyethane)dichloronickel(II); 4,4',4-tri-tert-butyl-2,2':6',2-terpyridine In N,N-dimethyl-formamide at 40℃; for 4h; | Procedure for Preparation of Very Long Chain Fatty Acids General procedure: For synthesis of very long chain fatty acids having chain lengths of 32-40 carbons (fatty acids C32-C40), DHA-Br (113 mg, 0.3 mmol) and methyl ω-bromoalkanoate(0.9 mmol) were dissolved in 2 mL of dry DMF and NiCl2(glyme) (8 mg, 36 μmol), terpyridine (13 mg, 32 μmol), and manganese powder (73 mg, 1.3 mmol) were added. The suspension was mixed, purged with argon, and stirred at 40°C for 4 hours. The product isolated by extraction with diethyl ether was subjected to silica gel chromatography (elution with diethyl ether-hexane 3:97 [v/v]) to provide the elongated ester (yields, 70-75% based on DHA-Br added, purity >90%). Subsequent treatment with 0.3 M NaOH in 85% ethanol under argon at 60°C for 1 hours afforded the elongated acid, which was further purified on a second silica gel column (elution with diethyl ether-hexane-acetic acid 10:90:0.05 (v/v/v); fractions monitored either by TLC or by GC-MS after methylation). In this way, were obtained C32, C34, C36, C38, C40 as well as [2,2,3,3,4,4-2H6]C32 having >98% purity as judged by TLC and by GC-MS analysis of their methyl ester derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.22 mmol | With manganese; (1,2-dimethoxyethane)dichloronickel(II); 4,4',4-tri-tert-butyl-2,2':6',2-terpyridine In N,N-dimethyl-formamide at 40℃; for 4h; | Procedure for Preparation of Very Long Chain Fatty Acids General procedure: For synthesis of very long chain fatty acids having chain lengths of 32-40 carbons (fatty acids C32-C40), DHA-Br (113 mg, 0.3 mmol) and methyl ω-bromoalkanoate(0.9 mmol) were dissolved in 2 mL of dry DMF and NiCl2(glyme) (8 mg, 36 μmol), terpyridine (13 mg, 32 μmol), and manganese powder (73 mg, 1.3 mmol) were added. The suspension was mixed, purged with argon, and stirred at 40°C for 4 hours. The product isolated by extraction with diethyl ether was subjected to silica gel chromatography (elution with diethyl ether-hexane 3:97 [v/v]) to provide the elongated ester (yields, 70-75% based on DHA-Br added, purity >90%). Subsequent treatment with 0.3 M NaOH in 85% ethanol under argon at 60°C for 1 hours afforded the elongated acid, which was further purified on a second silica gel column (elution with diethyl ether-hexane-acetic acid 10:90:0.05 (v/v/v); fractions monitored either by TLC or by GC-MS after methylation). In this way, were obtained C32, C34, C36, C38, C40 as well as [2,2,3,3,4,4-2H6]C32 having >98% purity as judged by TLC and by GC-MS analysis of their methyl ester derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (11aS)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]-benzodiazepine-3,11-dione With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 10-bromodecanoic acid methyl ester In N,N-dimethyl-formamide at 0 - 20℃; | General procedure: The solution of 6a (0.5 g, 2.31 mmol) in anhydrous DMF (10 mL) wasadded sodium hydride (0.18 g, 4.62 mmol) at 0 C, the mixture wasstirred for 0.5 h under this temperature, then 7a (or 7b, 9a-9g, 2.31mmol) was added, the mixture was stirred for another 1 h at roomtemperature. Then 40 mL water was added, stirred for 5 min, the solutionwas extracted with ethyl acetate (50 mL × 3). The ethyl acetatelayer was concentrated in vacuum to give a yellow oil 8a (or 8b, 10a-10g). After that, 8a (or 8b, 10a-10g, 2 mmol) was dissolved in anhydrousmethanol (20 mL), hydroxylamine hydrochloride (0.56 g, 8 mmol)and potassium hydroxide (0.90 g, 16 mmol) were added at 0 C, andstirred for 3 h at room temperature. The resulting mixture was extractedand filtered, and the filtrate was concentrated and dried in vacuum,resulting in a yellow viscous solid. Then 30 mL water was added, theaqueous was acidified to pH 4-5 with dilute hydrochloric acid (1 M),and extracted with dichloromethane (50 mL × 3). The dichloromethanelayer was concentrated and dried in vacuum and the residue was purifiedby flash chromatography (silica gel, 200-300 mesh, DCM: MeOH =50: 1 ~ 20: 1) to give compounds A1-A9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; potassium iodide In N,N-dimethyl-formamide at 70℃; for 12h; |
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 :