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CAS No. : | 629-72-1 | MDL No. : | MFCD00000229 |
Formula : | C15H31Br | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JKOTZBXSNOGCIF-UHFFFAOYSA-N |
M.W : | 291.31 | Pubchem ID : | 12394 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 13 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 82.09 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -1.91 cm/s |
Log Po/w (iLOGP) : | 4.7 |
Log Po/w (XLOGP3) : | 8.68 |
Log Po/w (WLOGP) : | 6.47 |
Log Po/w (MLOGP) : | 5.65 |
Log Po/w (SILICOS-IT) : | 6.37 |
Consensus Log Po/w : | 6.37 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 1.0 |
Egan : | 1.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -6.26 |
Solubility : | 0.000161 mg/ml ; 0.000000554 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -8.56 |
Solubility : | 0.000000805 mg/ml ; 0.0000000028 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -6.78 |
Solubility : | 0.0000485 mg/ml ; 0.000000166 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.09 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H317-H319 | 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 |
---|---|---|
With hexane; hydrogen bromide | ||
With hydrogen bromide at 120℃; | ||
With hydrogen bromide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With bromine; mercury(II) oxide In tetrachloromethane for 2h; Heating; | |
80% | With bromine; mercury(II) oxide In tetrachloromethane 1.) room temperature, 30 min, 2.) reflux, 2 h; | |
(i) TlOEt, (ii) Br2; Multistep reaction; |
With Bromotrichloromethane; 2-mercaptopyridine-1-oxide sodium salt 2.) reflux; Yield given. Multistep reaction; | ||
With bromine; thallium (I) ethoxide 1.) hexane, 2.) reflux, 3 h; Yield given. Multistep reaction; | ||
With bromine; mercury(II) oxide In various solvent(s) | ||
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide 2: dmap; Bromotrichloromethane; 2-mercaptopyridine-1-oxide sodium salt / 4 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In toluene for 120h; Heating; | |
98% | In toluene for 120h; Heating / reflux; | To a suspension of pentadecylphosphonium bromide (5.52g, 9. 8mmol ; prepared from [1-BROMOPENTADECANE] and triphenylphosphine, refluxed in toluene for 5 days, 98%) in THF [(20ML)] was added dropwise [NAHMDS] (0.6M in toluene, [15ML,] 9. [2MMOL)] at-75°C under nitrogen atmosphere. The solution was gradually warmed to [0°C] and stirred for lh. To this solution, which was cooled down to-75°C again, aldehyde 3 (2.472g, [7MMOL)] in [8ML] THF was added dropwise over 30 min. After the reaction mixture was stirred at rt for 2h, the reaction was quenched by addition of saturated [NH4C1] [(100ML)] and extracted with ether. The organic extract was washed with brine, dried over [NA2S04,] filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with EtOAc-PE (10%) to afford 3.44g [(85%)] Z-olefin 4 as a colorless [OIL.'H] NMR [(CDC13,] 500 MHz) : 8 7.34-7. [31] (m, 5H, [C6H5),] 5.47 (after decoupling, d, [J=LOHZ,] 1H, vinyl H next to [CH2),] 5.42 (m, 1H, NH), 5.27 (t, J=9.8Hz, [1H,] vinyl H next to CH), 5.09 (m, 2H, [CH2PH),] 4.58 (m, 1H), 3.67 (m, 2H), 2. 11 (m, . 2H), 1.73 (m, 2H), 1.25 (s, 22H), 0.89 (s, 12H), 0.05 (s, 3H), 0.04 (s, 3H). 13C NMR [(CDC13,] 75MHz): 8 [155.] [71,] 136.96, 132.39, 129.96, 128.52, 128.16, 128.02, 66.59, 60.34, 60.31, 47.24, 38.06, 32.21, 29.99, 29.85, 29.69, 29.65, 29.55, 29.50, 27.96, 26.17, 22.99, 18.43, 14.42,-5. 15. |
98% | In toluene for 120h; Heating / reflux; | 1 Preparation of Z-Olefin (4) To a suspension of pentadecylphosphonium bromide (5.52 g, 9.8 mmol; prepared from 1-bromopentadecane and triphenylphosphine, refluxed in toluene for 5 days, 98%) in THF(20 ml) was added dropwise NaHMDS (0.6M in toluene, 15 ml, 9.2 mmol) at -75° C. under nitrogen atmosphere. The solution was gradually warmed to 0° C. and stirred for 1 h. To this solution, which was cooled down to -75° C. again, aldehyde 3 (2.472 g, 7 mmol) in 8 ml THF was added dropwise over 30 min. After the reaction mixture was stirred at rt for 2 h, the reaction was quenched by addition of saturated NH4Cl(100 ml) and extracted with ether. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with EtOAc-PE (10%) to afford 3.44 g (85%) Z-olefin 4 as a colorless oil. |
87% | In acetonitrile at 80℃; for 120h; Inert atmosphere; | 16 Example 16 Example 16 Synthesis of pentadecyltriphenylphosphonium bromide (16*) A solution of 1-bromopentadecane (30.0 g, 103 mmol) and triphenylphosphine (27.02 g, 103 mmol) in MeCN (200 mL) was refluxed at 80 °C for five days. After removal of the solvent in vacuo, Et2O (30 mL) was added and the resulting white precipitate was filtered off, washed with Et2O and dried on high vacuum for 24 h to give pentadecyltriphenylphosphonium bromide (16*) (49.66 g, 87%) as a white powder. |
87% | In acetonitrile at 80℃; for 120h; Inert atmosphere; | B.4 Example B.4: Synthesis of pentadecyltriphenylphosphonium bromide (16*) Example B.4: Synthesis of pentadecyltriphenylphosphonium bromide (16*)A solution of 1 -bromopentadecane (30.0 g, 103 mmol) and triphenylphosphine (27.02 g, 103 mmol) in MeCN (200 mL) was refluxed at 80 °C for five days. After removal of the solvent in vacuo, Et2O (30 mL) was added and the resulting white precipitate was filtered off, washed with Et2O and dried on high vacuum for 24 h togive pentadecyltriphenylphosphonium bromide (16*) (49.66 g, 87%) as a white powder. |
84% | In acetonitrile for 36h; Heating; | |
80% | In acetonitrile for 12h; Heating; | |
80% | In acetonitrile for 30h; Heating; | |
at 150℃; for 12h; | ||
In toluene for 120h; Heating; | ||
In xylene Heating; | ||
In chlorobenzene at 125℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile for 0.5h; Ambient temperature; | ||
In acetone at 20℃; for 48h; | 2.1.1 General procedure of 1-alkyl-1-azonia-4-azabicyclo[2.2.2]octane salts synthesis (3a-3k) General procedure: The compounds 3a-3k were prepared according to a previously reported method via treatment of 1,4-diazabicyclo[2.2.2]octane with appropriate haloalkanes in acetone solution. The experimental procedure for the synthesis can be found in Supplementary Information. 1H and 13C NMR spectra were consistent with those reported in the literature [29]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.7% | Stage #1: 1,2-dimethoxybenzene With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 2h; Stage #2: pentadecyl bromide In tetrahydrofuran; hexane at 210℃; for 5h; | Synthesis of veratrole-type urushiol derivatives General procedure: Synthesis of veratrole-type urushiol derivatives (VTUDs) was carried out according to the method of Niimura et al. [23] and Satoh et al. [24]. Exactly 3.82 ml veratrole (0.03 mol) was added to a solution (130 ml) of dry tetrahydrofuran (THF) and the mixture was stirred for 30 min at 0 °C. A solution of 28.2 ml n-BuLi (1.6 M solution in n-hexane, 0.045 mol) in 5 ml THF was slowly added to the mixture and then stirred successively for 1 h at 0 °C and for 1 h at room temperature. A solution (5.56 ml) of 1-bromoalkanes (0.045 mol), with different carbon chain lengths, was slowly poured into the solution and then refluxed for 5 h at 210 °C. The resulting mixture was added to a saturated NH4Cl solution (150 ml, twice) and partitioned with ethyl acetate (EtOAc; 200 ml, twice). The organic layer was washed with brine (200 ml, twice) and added to anhydrous K2CO3. After filtration, the organic layer was evaporated in vacuo at 35 °C. The concentrates was purified by silica gel (100 g, 2.3×67 cm) column chromatography eluting with toluene to give the VTUDs. Four VTUDs (3, 4, 5, and 6) were synthesized using 1-brompentane, 1-bromodecane, 1-bromopentadecane, and 1-bromoeicosane by the same procedure described above. |
2.7 g | With n-butyllithium In tetrahydrofuran; hexane for 40h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: pentadecyl bromide In tetrahydrofuran at 20℃; for 5h; Inert atmosphere; | 1.1; 2.1 Example 2, 1) Add 1.2g of compound A-0 into a dry 100ml four-necked flask, add 10ml of anhydrous THF, under the protection of argon, reduce to -78, add 4.8ml of n-butyllithium, and 2.5ml of hexamethylphosphorus Triamide; After the addition is complete, stir at -78°C for 0.5h; then add 1-bromopentadecane in tetrahydrofuran; react at room temperature for 5h; after quenching with water, concentrate, wash and extract the crude compound Purified by column chromatography to obtain compound A-2a (2.22 g, yield 84%) |
76% | Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: pentadecyl bromide With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran; hexane at -78℃; for 24h; | 2.9. Synthesis of 2-(2-alkynyloxy)-tetrahydro-2H-pyrancompounds General procedure: To a stirred solution of tetrahydro-2-(2-proponyloxy)-2H-pyran(7.13 mmol) in dry THF (20 mL), n-BuLi (2.5 M, 17.83 mmol) in dryhexane (7.10 mL) was added dropwise while keeping the temperatureat-78 C. After 30 min, HMPA (5.0 mL) and 1-bromotridecane(7.13 mmol) or 1-bromopentadecane (7.13 mmol) was added dropwiseto the reaction mixture while maintaining the temperature at78 C. After 24 h, the reaction mixture was worked up by pouring alarge volume of water and extracting with diethyl ether (2×20 mL).The organic layer was washed with brine (1×20 mL) before drying(MgSO4). Filtration, rotoevaporation of the solvent and columnpurification with hexane-diethyl ether (9:1, v/v) solution afforded1.38 g (60% yield) of 2-(2-hexadecynyloxy)-tetrahydro-2H-pyranand 1.89 g (76% yield) of 2-(2-octadecynyloxy)-tetrahydro-2Hpyran. 2-(2-Octadecynyloxy)-tetrahydro-2H-pyran was obtained in a76% yield as colorless oil from the reaction 1.00 mL of tetrahydro-2-(2-propynoloxy)-2H-pyran (1.00 g, 7.13 mmol) and 2.00 mL of1-bromopentadecane (7.13 mmol) according to the general proceduredescribed above. IR (neat) max: 2925, 2854, 2222, 1466,1345, 1201, 1132, 1118, 1079, 1053, 1025 cm-1; 1H NMR (300 MHz,CDCl3) 4.81 (1H, t, J = 3.27 Hz), 4.24 (2H, m), 3.84 (1H, m), 3.52(1H, m), 2.20 (2H, m); 1.89-1.25 (32H, m), 0.87 (3H, t, J = 6.69 Hz);13C NMR (75 MHz) 96.57, 86.77 (s, C-3), 75.64 (s, C-2), 61.95,54.62 (t, C-1), 31.90, 30.27, 29.67 (×3), 29.61, 29.52, 29.348, 29.12,28.87, 28.75, 28.59, 28.16, 25.36, 22.67, 19.10, 18.80, 14.10 (q, C-18).GC-MS (70 eV) m/z (relative intensity); 350 (M+, 0.55), 295 (0.68),279 (1), 209 (2), 149 (5), 135 (14), 121 (17), 111 (39), 95 (59), 85(100), 81 (55), 77 (9), 67 (47), 55 (81). |
63% | Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: pentadecyl bromide In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | 25.A A. Synthesis of 2-octadec-2-ynoxytetrahydropyran (NP-PD-023) To a 250 mL oven-dried flask equipped with a stir bar was added 2-(2- propynyloxy)tetrahydro-2H-pyran (5.02 mL, 35.7 mmol, 1.00 eq), hexamethylphosphoramide (21.7 mL, 125 mmol, 3.50 eq) and THF (100 mL). The reaction mixture was cooled to -78 °C and stirred vigorously under Ar. n-Butyllithium (2.00 M in THF, 23.2 mL, 46.4 mmol, 1.30 eq) was added dropwise over a period of 15 minutes by way of an oven-dried pressure equalizing dropping funnel and the reaction was vigorously stirred at -78 °C for approximately 1 hour. Subsequently, 1-bromopentadecane (13.4 mL, 46.4 mmol, 1.30 eq) was added slowly dropwise over 10 minutes by way of a pressure equalizing dropping funnel after which the resulting reaction mixture was allowed to warm to room temperature overnight while stirring vigorously under Ar. The following day TLC indicated that all of the starting alkyne had been consumed. The reaction mixture was quenched with a saturated solution of ammonium chloride and then extracted three times into EtOAc. The organic phases were then combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. Subsequent purification of the resulting crude material by column chromatography (2%-10% EtOAc/hexane) afforded a clear oil (7.86 g, 22.4 mmol, 63% yield). |
63% | Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With n-butyllithium In tetrahydrofuran; hexane at -78 - -30℃; for 0.916667h; Inert atmosphere; Stage #2: pentadecyl bromide In tetrahydrofuran; hexane at -30 - 20℃; Inert atmosphere; | |
With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane 1.) -70 deg C, 1 h, 2.) -50 deg C, 5 h; | ||
With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium 1.) THF; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Bromotrichloromethane In tetrachloromethane at 20℃; for 0.0833333h; Irradiation; light source: tungsten; Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 77% 2: 83% | With Bromotrichloromethane In toluene at 110℃; for 0.75h; | |
1: 77% 2: 83% | With Bromotrichloromethane In toluene for 0.75h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 93% 2: 6% 3: 92% | With Bromotrichloromethane In benzene at 80℃; for 1h; | |
1: 93% 2: 92% | With Bromotrichloromethane In benzene for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Bromotrichloromethane; 2-mercaptopyridine-1-oxide sodium salt at 105℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Stage #1: furan With n-butyllithium In tetrahydrofuran at -78 - 0℃; for 1.5h; Stage #2: pentadecyl bromide In tetrahydrofuran at -78 - 20℃; | |
4.8 g (64%) | With n-butyllithium; ammonium chloride In tetrahydrofuran | 6 Preparation of 2-(pentadecyl)furan EXAMPLE 6 Preparation of 2-(pentadecyl)furan This example describes the preparation of 2-(pentadecyl)furan compound(1) according to Scheme 2A. A dry 50 ml round bottom flask charged with furan (1.40 g, 20.6 mmol) and THF (10 ml), was cooled to -78° C. and n-butyllithium (13.6 ml, 1.50 M in hexanes, 20.6 mmol) was added dropwise. The solution was stirred for 30 mm at -78° C., then warmed to 0° C. and placed in an ice bath for 1 h. The mixture was then cooled to -78° C. and 1-bromopentadecane 9 (5 g, 17.2 mmol) in THF (10 ml) were added dropwise. The resulting solution was stirred for 1 h, then warmed to room temp and stirred 12 h. The reaction was quenched with a saturated solution of NH4Cl (5 ml). The organic layer was separated and the aqueous layer extracted with ether (3*20 ml). The combined organic layers were washed with saturated NaHCO3 (1*20 ml), brine (1*20 ml), dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by flash chromatography on silica, eluding with hexanes to afford a oily liquid that was recrystallized from methanol (~ 50 ml/g, cooling to 5° C.) to afford 4.8 g (64%) of 2-(pentadecyl)furan (1). 1 H NMR: (CDCl3) (0.85) 3H, distorted t, J~ 7.2 Hz), 1.1-1.4 (24H, broad m), 1.57 (2H, quintet, J~ 7.2 Hz), 2.58 (2H, t, J 7.2 Liz), 5.99 (1H, dd, J~ 1, 3.0 Hz), 6.29 (1H, dd, J~ 1.8, 3.0 Hz), 7.29 (1H, dd, J~ 1, 1.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With dilithium tetrachlorocuprate; magnesium In tetrahydrofuran at 4℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: pentadecyl bromide With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In tetrahydrofuran; hexane at -78 - 50℃; for 20h; Stage #3: In methanol at 40℃; for 3h; | |
79% | Stage #1: pentadecyl bromide; 3-(tetrahydropyran-2'-yloxy)propyne With n-butyllithium In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane at 0 - 20℃; Stage #2: With p-toluenesulfonic acid monohydrate In methanol at 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium hydroxide; tetrabutylammomium bromide In tetrahydrofuran at 20℃; | |
With potassium carbonate; potassium iodide In acetone for 24h; Heating; | ||
With potassium hydroxide In tetrahydrofuran |
Stage #1: 4-hydroxy-benzaldehyde With sodium hydroxide In water at 20℃; for 0.25h; Stage #2: pentadecyl bromide In N,N-dimethyl-formamide at 20℃; for 72h; | ||
With tetrabutylammomium bromide; potassium hydroxide In tetrahydrofuran | ||
Stage #1: 4-hydroxy-benzaldehyde With potassium carbonate; potassium iodide In acetone for 2h; Inert atmosphere; Reflux; Stage #2: pentadecyl bromide for 24h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: N-(2,2-Dimethyl-1,3-dioxan-5-ylidene)-N-[(2'R)-2-(methoxymethyl)tetrahydro-1'H-1'-pyrrolyl]amine With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 2h; Stage #2: pentadecyl bromide In tetrahydrofuran; pentane at -100 - 20℃; Stage #3: With oxalic acid In diethyl ether for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With 1-n-butyl-3-methylimidazolim hexafluoroantimonate; potassium carbonate In acetonitrile at 115℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 59% 2: 4% | With 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 110℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: pentadecyl bromide In tetrahydrofuran at -78 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With lithium In hexane at -40℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: fluoromethyl phenyl sulfone With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: pentadecyl bromide In tetrahydrofuran; hexane at 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: xylene / Heating 2: KHMDS / -78 °C | ||
Multi-step reaction with 2 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C | ||
Multi-step reaction with 2 steps 1: 98 percent / toluene / 120 h / Heating 2: n-BuLi / tetrahydrofuran; hexane / 3 h / -75 - 20 °C |
Multi-step reaction with 2 steps 1.1: acetonitrile / 120 h / 80 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / 0 °C / Inert atmosphere 2.2: 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: toluene / 120 h / Heating 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2.2: 66 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 56 percent / 1-methylmorpholine N-oxide; OsO4; Na2SO3 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: pyridine; DMAP / 20 °C 5.1: TFA / methanol / 2 h / 0 °C 6.1: 301 mg / NaHCO3 / dioxane; aq. NaHCO3 7.1: 77 percent / AW300; TMSOTf / diethyl ether; tetrahydrofuran / 1 h / -30 °C 8.1: H2 / Pd/C / ethyl acetate; ethanol 9.1: pyridine; DMAP / 20 °C 10.1: TFA / CH2Cl2 / 0 - 20 °C 11.1: HBTu; NMM / CH2Cl2 / 20 °C 12.1: NaOMe / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: lithium; dioxane 2: Raney nickel; ethyl acetate / Hydrogenation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: copper chromite / 250 °C / 154457 Torr / Hydrogenation 2: hexane; HBr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With hydrogenchloride In tetrahydrofuran | (2S,3R)-2-(N,N-Dibenzylamino)-3-octadecanol (60): (2S,3R)-2-(N,N-Dibenzylamino)-3-octadecanol (60): Mg ribbon (237 mg, 9.75 mmol), dibromoethance (16 μL, 0.189 mmol) in THF (160 μL) were added to a two neck flask fitted with a reflux condenser. A 1/2 mL of a 1-bromopentadecane solution (970 mg, 3.33 mmol, 3.25 mL THF) was added. After the reaction had started the remainder was added dropwise. To the grayish solution, 50 (105 mg, 0.413 mmol) in THF (0.5 mL) was added dropwise. The reaction was allowed to stir overnight followed by the addition of H2 O (5 mL) and 0.1 N HCl until the solution became clear. The mixture was extracted with EtOAc (3*10 mL). The organic layer was washed with 5% NaHCO3 then satd. NaCl solutions and dried with MgSO4. The solvent was removed in vacuo to give an oil-solid mixture (750 mg). The crude material was purified by flash chromatography on silica (8:1 hexane/EtOAc, Rf =0.34) to give 120 mg of a solid. This solid was further purified by HPLC on silica (93:7 hexane/EtOAc) to give a colorless waxy solid (94.3 mg, 49% yield): [α]25D =+16.3 (cl, CHCl3); 1 H NMR (500 MHz, CDCl3) δ 0.88 (t, 3H, J=7.0 Hz), 1.10 (d, 3H, J=6.7 Hz), 1.16-1.41 (bm, 26H), 1.56 (m, 1H), 1.69 (m, 1H), 1.79 (m 1H), 2.72 (quin, 1H, J=6.7 Hz), 3.47 (d, 2H, J=13.8 Hz), 3.60 (m, 1H), 3.76 (d, 2H, J=13.8 Hz), 7.22 (m,2H), 7.30 (m,4H), 7.34 (m,4H); 13 C NMR (1 MHz) δ 8.67, 14.11, 22.68, 25.90, 29.35, 29.61, 29.64, 29.68, 29.69, 31.91, 34.27, 54.79, 57.26, 73.65, 2.89, 4.25, 4.77, 140.17; FABMS m/z 465 (M+H), 448 (M--H2 O), 464 (M--H), 388 (M--Ph), 224 (M--C16 H33 O); HRFABMS calcd for C32 H52 NO Mr 466.4049 (M+H), found Mr 466.4037. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In 3-mercaptopropionic acid ethyl ester | 43 3-Pentadecylthiopropan-1-ol phosphoric acid monocholine ester EXAMPLE 43 3-Pentadecylthiopropan-1-ol phosphoric acid monocholine ester 1-Bromopentadecane is reacted in the usual way with ethyl β-mercaptopropionate and the syrup obtained reduced with lithium aluminium hydride to give a yield of 84% of theory of 3-pentadecylthiopropanol; m.p. 36°-39° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.2% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; | |
With potassium carbonate In water; acetone | 1 Synthesis of 3,5-dipentadecyloxybenzamidine (EXAMPLE 1) Synthesis of 3,5-dipentadecyloxybenzamidine 3,5-dihydroxybenzonitrile (0.50 g), 1-bromopentadecane (2.70 g), potassium carbonate (2.56 g), and 30 ml of acetone were mixed and the mixture was heated overnight under reflux. After water was added, the mixture was extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed by evaporation to obtain 0.33 g of 3,5-dipentadecyloxybenzonitrile as colorless crystals. | |
0.33 g | With potassium carbonate In acetone Reflux; | 3,5-Dihydroxybenzonitrile in an amount of 0.50 g, 2.70 g of 1-bromopentadecane, 2.56 g of potassium carbonate and 30 ml of acetone were mixed, and the mixture was heated at reflux overnight. Thereafter, water was added to the mixture, and the reaction mixture was subjected to extraction with methylene chloride, washing with water, and then to drying with anhydrous magnesium sulfate. The solvent was distilled away, to obtain 0.33 g of 3,5-dipentadecyloxybenzonitrile as colorless crystal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: pentadecyl bromide With magnesium In diethyl ether for 3h; Inert atmosphere; Stage #2: With Trimethyl borate In diethyl ether at -78 - 20℃; Inert atmosphere; Stage #3: With hydrogenchloride; water In diethyl ether at 20℃; | III III. Pentadecylboronic Acid; To a dry 3-necked round bottom flask equipped with a reflux condenser flushed with argon was added magnesium turnings (1.35 g) followed by addition of 2.3 mL of dry ether and one crystal of iodine. 1-Bromopentadecane a (5 mL, 5.0 g, 17.3 mmol) was dissolved into 6 mL ether and slowly added over one hour to the magnesium under ether. After complete addition of the bromide, the solution was allowed to stir for 2 hours without external heating.A dry 250 mL round bottom flask cooled to -78° C. equipped with a 250 mL pressure equalizing addition funnel was flushed with argon followed by addition of 40 mL dry ether and 2.0 mL (17.5 mmol) trimethylborate. Compound b was then added dropwise over one hour. The solution was stirred for an additional hour before removing the cold bath and allowing the reaction to warm to room temperature. 10% HCl (50 mL) was then added dropwise to the reaction flask at room temperature. After 15 minutes of additional stirring, the biphasic solution was extracted into ether. The ethereal solutions were dried over MgSO4 and the ether removed under reduced pressure. The resulting white solid was purified as follows by adding water (90° C.) to dissolve the products, the solution was then cooled to 4° C. to allow the boronic acid to precipitate as a white solid. This was filtered, the solid collected, and then washed with hexanes 60° C.). The flask was placed in the freezer for 1 hour. The precipitate was filtered, collected, and dried under vacuum to provide Inhibitor C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.6% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; Inert atmosphere; | 9.1 Ethyl 3,4,5-trihydroxybenzoate (5.003 g, 25.245 mmol) and potassium carbonate (12.245 g, 88.600 mmol) were agitated in DMF (35 ml) in the presence of 1-bromopentadecane (25.5 ml, 87.972 mmol) under an argon atmosphere at 90 °C. After the reacted product was extracted into an organic phase using chloroform-water, the organic phase was washed twice by water, further washed by saturated sodium thiosulfate solution, and dried by anhydrous magnesium sulfate. After the organic phase was filtrated, the filtrate was condensed. Thus obtained residue was recrystalized twice by dichloromethane-methanol, thus, a desired compound (ethyl 3,4,5-tris(pentadecyloxy)benzoate, OR in the formula [A] is pentadecyloxy) (white powder, 18.758 g, yield 89.6 %) was obtained. 1HNMR, 13CNMR and MALDI-TOF-MS of the obtained compound were measured and the following data was obtained. 1 H NMR (400 MHz, CDCl3, TMS): δ(ppm) 0.86-0.895 (m, 9H, CH3), 1.26-1.40 (m, 69H, CH3+CH2), 1.43-1.51 (m, 6H, CH2), 1.70-1.84 (m, 6H, CH2), 3.99-4.03 (m, 6H, ArOCH2), 4.35 (q, J=7.1 Hz, 2H, CH3CH2O), 7.25 (s, 2H, arom. H). 13 C NMR (100.4 MHz, CDCl3): δ(ppm) 14.10, 14.12, 14.40, 22.685, 22.705, 26.06, 26.08, 29.315, 29.32, 29.36, 29.365, 29.37, 29.40, 29.565, 29.57, 29.63, 29.64, 29.66, 29.68, 29.70, 29.705, 29.71, 29.73, 29.74, 29.75, 30.32, 30.325, 31.92, 31.93 (aliphatic), 60.94, 69.18, 73.475 (ether), 108.00, 125.03, 142.33, 152.79 (aromatic), 166.47 (carbonyl). MALDI-TOF-MS (matrix: 2,5-dihydroxybenzoic acid): m/z=829.01 (M+), 852.03 ([M+Na]+) |
89.6% | With potassium carbonate In N,N-dimethyl-formamide at 90 - 100℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 60℃; for 18h; | |
72% | With sodium hydride In tetrahydrofuran at 0 - 70℃; for 18.6667h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol at 140℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With n-butyllithium In tetrahydrofuran; hexane at 23℃; for 0.333333h; | 17 Example 17: preparation of 2-(dimethylamino)-4-hexadecyl-6- methoxypyrimidin-5-ol (Compound K); 4-hexadecyl-6-methoxy-N,N-dimethylpyrimidin-2-amine:; To a stirred solution containing 1.12 g (6.70 mmol) of 4-methoxy-N,N,6-trimethylpyrimidin- 2-amine and 2.62 g (6.70 mmol) of 1-pentadecane in 20 mL of anhydrous THF were added 6.28 mL (10.1 mmol) of 1.6 M n-BuLi in hexanes. The reaction mixture was stirred for 20 min at 23 °C. The reaction mixture was quenched with saturated aqueous ammonium chloride and poured into 100 mL of water. The compound was extracted with two 80-mL portions of ethyl acetate. The combined organic layer was washed with one 80-mL portion of brine, dried (MgS04) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 x 5 cm). Elution with 9: 1 hexanes-ethyl acetate afforded the expected product as white solid: yield 1.58g (62%); mp: 49-50 °C; silica gel TLC Rf 0.5 (9: 1 hexanes-ethyl ether); 1H-NMR(CDC13) δ 0.86 (t, 3H, J = 6.8 Hz), 1.30-1.20 (br m, 26H), 1.63 (quint, 2H, J = 7.2 Hz), 2.46 (dd, 2H, J = 7.6, 7.6 Hz), 3.14 (s, 6H), 3.85 (s, 3H) and 5.77 (s, 1H); 13C NMR(CDC13) δ 14.10, 22.67, 28.49, 29.33, 29.49, 29.55, 29.64, 29.68, 29.68, 29.68, 29.68, 29.68, 29.68, 29.68, 31.90, 36.78, 37.83, 37.83, 52.75, 93.03, 162.28, 179.25 and 171.93. |
62% | With n-butyllithium In tetrahydrofuran; hexane at 23℃; for 0.333333h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With n-butyllithium In tetrahydrofuran; pentane at -78 - 23℃; for 0.5h; | 14 Example 14: preparation of 2-(dimethylamino)-4-hexadecyl-6-methylpyrimidin- 5-ol (Compound J); Lzyloxy)-2-(2,5-dimethyl- 1 H-pyrrol- 1 -yl)-4-hexadecyl-6-methylpyrimidine; To a stirred solution at -78 °C containing 1.00 g (3.25 mmol) of 5-(Benzyloxy)-2-(2,5- dimethyl-lH-pyrrol-l-yl)-4,6-dimethylpyrimidine and 630 (2.16 mmol) of 1- bromopentadecane in 20 mL of anhydrous THF were added 2.70 mL (4.32 mmol) of a 1.60 M solution of n-BuLi in pentane. The reaction mixture was stirred at 23 °C for 30 min. The reaction was quenched with saturated aqueous ammonium chloride and then poured into 70 mL of water. The mixture was then extracted with two 70-mL portions of diethyl ether. The combined organic layer was then washed with a 100-mL portion of brine, dried (MgS04) and then concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 x 5 cm). Elution with 4: 1 hexanes-diethyl ether afforded the expected product as a colorless oil: yield 269 mg (24%); silica gel TLC Rj 0.5 (4: 1 hexanes-diethyl ether); 1H NMR(CDC13) 50.89 (t, 3H, J = 7.2 Hz), 1.20-1.30 (m, 26H), 1.75 (quint, 2H, J = 7.2 Hz), 2.29 (s, 6H), 2.47 (s, 3H), 2.76 (dd, 2H, J = 8.0, 8.0 Hz), 4.89 (s, 2H), 5.85 (s, 2H) and 7.30-7.42 (m, 5H); 13C NMR (CDC13) δ 14.08, 14.30, 14.30, 19.27, 22.66 27.72, 29.33, 29.40, 29.50, 29.55, 29.63, 29.63, 29.63, 29.67, 29.67, 29.67, 29.67, 31.61, 31.89, 75.72, 107.91, 128.01, 128.22, 128.72, 129.30, 129.30, 136.22, 147.35, 147.35, 152.59, 161.59 and 165.09; mass spectrum (APCI), m/z 518.4113 (M+H)+ (C34H52N30 requires 518.4110). |
24% | With n-butyllithium In tetrahydrofuran; pentane at -78 - 23℃; for 0.5h; Inert atmosphere; | 6 5.1.6 5-Benzyloxy-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4-hexadecyl-6-methylpyrimidine (9) To a stirred solution at -78 °C containing 1.00 g (3.25 mmol) of 5-benzyloxy-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyrimidine (7) and 630 μL (630 mg; 2.16 mmol) of 1-bromopentadecane in 20 mL of anhyd THF was added 2.70 mL (4.32 mmol) of a 1.60 M solution of n-BuLi in pentane. The reaction mixture was stirred at 23 °C for 30 min. The reaction was quenched with satd aq ammonium chloride and then poured into 70 mL of water. The mixture was then extracted with two 70-mL portions of ether. The combined organic layer was washed with 100 mL of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15 * 5 cm). Elution with 4:1 hexanes/ether afforded 9 as a colorless oil: yield 269 mg (24%); silica gel TLC Rf 0.5 (4:1 hexanes/ether); 1H NMR (CDCl3) δ 0.89 (t, 3H, J = 7.2 Hz), 1.20-1.30 (m, 26H), 1.75 (quint, 2H, J = 7.2 Hz), 2.29 (s, 6H), 2.47 (s, 3H), 2.76 (dd, 2H, J = 8.0, 8.0 Hz), 4.89 (s, 2H), 5.85 (s, 2H) and 7.30-7.42 m, 5H); 13C NMR (CDCl3) δ 14.1, 14.30, 14.30, 19.3, 22.7, 27.7, 29.3, 29.4, 29.50, 29.55, 29.63, 29.67, 31.6, 31.9, 75.7, 107.9, 128.0, 128.5, 128.7, 129.3, 136.2, 147.4, 152.6, 161.6 and 165.1; mass spectrum (APCI), m/z 518.4113 (M+H)+ (C34H52N3O requires 518.4110). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 2,3-dihydro-1,4,6-trimethylpyrrolo<2,3-b>pyridine With n-butyllithium In tetrahydrofuran; hexanes at -78℃; Inert atmosphere; Stage #2: pentadecyl bromide In tetrahydrofuran; hexanes at -78 - 20℃; for 16h; Inert atmosphere; regioselective reaction; | 4.1.10. 1,4-Dimethyl-6-hexadecyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (4c) To a solution of 277 mg (1.71 mmol) of compound 5 in 5 mL of THF was added 1.71 mL (2.73 mmol, 1.6 M in hexanes) of n-BuLi followed by 518 μL (1.79 mmol) of 1-bromononane at -78 °C. The reaction mixture was slowly warmed to room temperature and stirred for another 16 h. The reaction mixture was quenched by the addition of 10 mL of satd aq NH4Cl at 0 °C. The mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (25 × 3.2 cm). Elution with 10:1 hexanes/ethyl acetate gave the product 4c as a white solid: yield 330 mg (52%); mp 43-45 °C; silica gel TLC Rf 0.25 (8:1:1 hexanes/ethyl acetate/MeOH); 1H NMR (CDCl3) δ 0.88 (t, 3H, J = 7.2 Hz), 1.25-1.31 (m, 28H), 1.66 (quint, 2H, J = 7.6 Hz), 2.08 (s, 3H), 2.55 (t, 2H, J = 8.0 Hz), 2.80 (t, 2H, J = 8.4 Hz), 2.90 (s, 3H), 3.38 (t, 2H, J = 8.4 Hz) and 6.13 (s, 1H); 13C NMR (CDCl3) δ 14.1, 18.0, 22.7, 24.4, 29.38, 29.38, 29.57, 29.62, 29.65, 29.68, 29.72, 29.72, 29.72, 29.72, 29.72, 29.72, 30.0, 32.0, 33.2, 38.1, 52.4, 112.4, 118.2, 141.0, 159.1 and 163.7; mass spectrum, m/z 372.3 (M+) (theoretical 372.4); mass spectrum (APCI), m/z 373.3574 (M+H)+ (C25H45N2 requires 373.3583). |
52% | With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 16h; | 10 1,4-dimethyl-6-hexadecyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine followed by 518 μL (1.79 mmol) of 1 -bromononane at -78 °C. The reaction mixture was slowly warmed to room temperature and stirred for another 16 h. The reaction mixture was quenched by the addition of 10 mL of sat aq NH4Cl at 0 °C. The mixture was extracted with EtOAc. The combined organic layer was trashed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by flash chromatography on a silica gel column (25 3.2 cm). Elution with 10:1 hexanes/ethyl acetate gave the product as a white solid: yield 330mg (52%); mp 43-45 °C; silica gel TLC Rf 0.25 (8:1:1 hexanes/ethyl acetate/MeOH); 1HNMR (CDCl3) δ 0.88 (t, 3H, J= 7.2 Hz), 1.25-1.31 (m, 28H), 1.66 (quint, 2H, J= 7.6 Hz), 2.08 (s, 3H), 2.55 (t, 2H, J= 8.0 Hz), 2.80 (t, 2H, J= 8.4 Hz), 2.90 (s, 3H),3.38 (t, 2H, J= 8.4 Hz) and 6.13 (s, 1H); 13C NMR (CDCl3) δ 14.1, 18.0, 22.7, 24.4, 29.38,29.38, 29.57, 29.62, 29.65, 29.68, 29.72, 29.72, 29.72, 29.72, 29.72, 29.72, 30.0, 32.0, 33.2,38.1, 52.4, 112.4, 118.2, 141.0, 159.1 and 163.7; mass spectrum, m/z 372.3 (M)+ theoretical372.4); mass spectrum (APCI), rn/z 373.3574 (M + H)+ (C25H45N2 requires 373.3583). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With potassium carbonate In ethyl acetate at 70℃; for 12h; Reflux; | Synthesis of N-(2-(dialkylamino) ethyl)-4-methoxybenzamide (II) General procedure: To, ethyl acetate (10 mL) solution of N-(2-Amino-ethyl)-4-methoxy-benzamide ( 0.67 g, 3.45 mmol) K2CO3 (2.34 g, 13.8mmol) and various alkyl bromides, (CnH2n+1Br, here n=2-18, 8.625mmol) were added. The whole mixture was refluxed at 70ºC for 12 hrs. After washed with water (2 x 20mL). The organic layer dried with anhydrous sodium sulphate and concentrated in vacuum.Column chromatographic purification (using 60-120 mesh silica gel) of the residue afforded N-(2-(dialkylamino) ethyl)-4-methoxybenzamides (II, in Scheme 1). |
57% | With potassium carbonate In ethyl acetate at 70℃; for 12h; | Synthesis of N-(2-(dialkylamino) ethyl)-4-methoxybenzamide(3): General procedure: To,ethyl acetate (10 mL) solution of N-(2-Amino-ethyl)-4-methoxy-benzamide (2, 0.67g, 3.45 mmol) K2CO3(2.34 g, 13.8mmol) and various alkyl bromides, (CnH2n+1Br,here n=2-18, 8.625 mmol) were added. The whole mixture was refluxed at 70 Cfor 12 hrs. After washing with water (2 x 20mL) the organic layer was dried with anhydrous sodium sulphateand concentrated in vacuum.Column chromatographic purification (using 60-120mesh silica gel) of the residue afforded N-(2-(dialkylamino) ethyl)-4-methoxybenzamides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (S)-pent-1-en-4-yn-3-ol With n-butyllithium In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane at -78 - -30℃; for 3h; Inert atmosphere; Stage #2: pentadecyl bromide In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane at 20℃; for 48h; Inert atmosphere; | 6 (S)-Pentadec-1-en-4-yn-3-ol 6a General procedure: (S)-1-Penten-4-yn-3-ol l (2.46 g, 2.5 mL, 30 mmol) and HMPA (32.6 g, 31.8 mL, 180 mmol) were dissolved in 80 mL of THF and cooled to -78 °C under a nitrogen atmosphere. n-BuLi (2.40 M in hexanes, 26.25 mL, 63 mmol) was then added dropwise to the mixture. The resulting heterogeneous solution was stirred for 3 h at -30 °C. A solution of 1-bromodecane (6.7 g, 6.27 mL, 30.0 mmol) in 10 mL of THF was then added dropwise to the solution, and the reaction mixture was stirred for 48 h at room temperature. After quenching with 40 mL of aqueous saturated ammonium chloride, the reaction solution was extracted with ether (50 mL × 3). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. The residue was then purified by flash chromatography (hexanes/ether, 15:1, v/v) to produce 4.11 g of (S)-pent-1-en-4-yn-3-ol as a yellow oil in 60.5% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrabutylammomium bromide; potassium hydroxide In N,N-dimethyl-formamide Reflux; | 4.3.1 General procedure for synthesis of compounds 3a-k General procedure: 1,4′-Diazaflavone (2) (∼0.68mmol for each) was dissolved in 5mL of DMF. Stoichiometric amount of KOH was added to the reaction flask. n-Bromoalkanes (1-bromopentane, 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodecane, 1-bromoundecane, 1-bromododecane, 1-bromotridecana, 1-bromotetradecane, and 1-bromopentadecane, 1.50mmol each) were added after conversion of dark orange colored mixture to dark green-brown. Also, catalytic amount of TBAB was used for compound 3k because of unmixed phases. Then, all solutions were refluxed separately for 6-12h [15]. On completion of the reaction, followed by TLC examination, the mixture was purified by column chromatography (column, length 30cm, diameter 2cm) on silica gel (25g, Merck, 230-400mesh). The column was eluted successively with the following solvents and solvent mixtures: hexane (30mL), ether (30mL), ether-ethyl acetate (1:1, 50mL), ethyl acetate (30mL) and ethyl acetate-methanol (8:1, 90mL) and methanol (30mL). Fractions (5-10mL each) were collected and monitored by analytical TLC. The desired violet oils or amorphous solids 3a-k were obtained from fractions 6-13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.3 g | With potassium carbonate In acetonitrile at 60℃; for 7h; | 1 methyl 3-(pentadecyloxy)benzoate (Compound 1) Example 1 methyl 3-(pentadecyloxy)benzoate (Compound 1) Methyl 3-hydroxy benzoate (2.7g) was dissolved in acetonitrile (30 mL) and potassium carbonate (4.8g) and 1-bromopentadecane (5.1g) were added thereto, followed by stirring at 60°C for 7 hours. After cooling of the reaction solution, it was diluted with ethyl acetate and filtered through Celite (brand name). The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→8:2) to obtain the title compound (6.3g) having the following physical property values. TLC : Ref 0.75 (hexane: ethyl acetate=8:2); 1H-NMR(CDCl3): δ 0.88 (t, J=6.9Hz, 3H), 1.15-1.63 (m, 24H), 1.70-1.85 (m, 2H), 3.91 (s, 3H), 3.99 (t, J=6.6Hz, 2H), 7.08 (ddd, J=7.8, 2.4, 0.9Hz, 1 H), 7.32 (t, J = 7.8Hz, 1H), 7.53 (dd, J=2.4, 1.5Hz, 1H), 7.60 (ddd, J=7.8, 1.5, 0.9Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.7 g | Stage #1: m-Toluic acid With lithium diisopropyl amide In tetrahydrofuran at 20℃; for 1h; Stage #2: pentadecyl bromide at 20℃; for 21h; | 5 3-hexadecylbenzoic acid (Compound 5) Example 5 3-hexadecylbenzoic acid (Compound 5) Meta-toluic acid (4.0g) was dissolved in tetrahydrofuran (98mL). Thereto, 2M lithium diisopropylamide (59 mL) was added at room temperature, followed by stirring for 1 hour. Thereto, 1-bromo pentadecane (9.4mL) was added, followed by stirring at room temperature for 21 hours. The reaction solution was poured to 1N hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain the title compound (3.7g) having the following physical property values. TLC:Rf0.44 (hexane:ethyl acetate =2:1); 1H-NMR(CDCl3): δ 0.88 (t, J=6.9Hz, 3H), 1.19-1.32 (m, 27H), 1.61-1.66 (m, 2H),2.66 (t, J=7.8Hz, 2H), 7.34-7.43 (m, 2H), 7.90-7.92 (m, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 6,12-di(thiophen-2-yl)-5,6,11,12-tetrahydroindolo[3,2-b]carbazole With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: pentadecyl bromide In N,N-dimethyl-formamide for 15h; Inert atmosphere; | 4.3. General procedure for the synthesis of 5,11-dialkyl-6,12-di(het)aryl-5,6,11,12-tetrahydroindolo[3,2-b]carbazole (2a-f) General procedure: KOt-Bu (80 mmol, 9 g; for alkylation of compound 1a) or a powder of NaOH (80 mmol, 3.2 g; for alkylation of 1b,c) was added in one portion to a suspension of the corresponding indolo[3,2-b]carbazole1 (20 mmol) in dry DMF (120 ml) and the mixture was stirred at room temperature under an argon atmosphere for 0.5 h. The appropriate alkyl bromide (80 mmol) was added dropwise to the resulting dark-green suspension and the reaction mixture was stirred for 15 h. After that time the reaction mixture was poured into50% (v/v) aqueous ethanol (250ml) and stirred for 1 h. The alkylated products 2 were collected by filtration, washed with ethanol (520 ml) and dried at 110 °C. The crude products were quite suitable for the next step of oxidation without further purification. The analytical samples of 2 were obtained by crystallization of crude materials from a mixture (10:1) of ethyl acetate/chloroform. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 15% 2: 45% | Stage #1: 3-(benzyloxy)-6-N,N-dimethylamino-2,4,5-trimethylpyridine With n-butyllithium; potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 0.5h; Stage #2: pentadecyl bromide In tetrahydrofuran at 0℃; for 0.5h; | 6 4.1.4 3-(Benzyloxy)-6-N,N-dimethylamino-2-hexadecyl-4,5-dimethylpyridine (13b) and 3-(Benzyloxy)-6-N,N-dimethylamino-4-hexadecyl-2,5-dimethylpyridine (14b) To a stirred solution containing 350 mg (1.29mmol) of 12 and 217mg (1.93 mmol) of KOtBu in 18mL of anhyd THF at -78°C was added 1.03 mL (2.58 mmol) of a 2.5 M solution of n-BuLi in hexane. The reaction mixture was stirred at -78°C for 30 min and then 449μL (1.55 mmol) of 1-bromopentadecane was added. The reaction mixture was stirred at 0°C for another 30min, then quenched with satd aq ammonium chloride and then extracted with 150mL of EtOAc. The combined organic phase was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (30×2cm). Elution with hexane followed by elution with 96:4 hexane/Et2O afforded 13b and 14b as yellowish oils: yields 93mg (15%) and 279mg (45%), respectively; silica gel TLC Rf 0.54 (4:1 hexane/Et2O) and Rf 0.44 (4:1 hexane/Et2O); (13b) 1H NMR (CDCl3) δ 0.88 (t, 3H, J=6.8Hz), 1.23-1.32 (br m, 26H), 1.74 (m, 2H), 2.18 (s, 3H), 2.19 (s, 3H), 2.72-2.77 (m, 8H), 4.73 (s, 2H) and 7.32-7.48 (m, 5H); 13C NMR (CDCl3) δ 13.3, 14.3, 15.0, 22.9, 28.8, 29.6, 29.82, 29.83, 29.84, 29.89, 32.08, 32.11, 42.8, 75.5, 121.5, 127.9, 128.1, 128.7, 137.7, 140.3, 147.4, 149.6 and 158.2; mass spectrum (APCI), m/z 481.4159 (M+H)+ C32H53N2O requires 481.4158); (14b) 1H NMR (CDCl3) δ 0.87 (t, 3H, J=7.2Hz), 1.21-1.38 (br m, 26H), 1.49 (m, 2H), 2.21 (s, 3H), 2.44 (s, 3H), 2.59 (m, 2H), 2.75 (s, 6H), 4.76 (s, 2H) and 7.30-7.48 (m, 5H); 13C NMR (CDCl3) δ 14.3, 14.5, 19.6, 22.9, 27.7, 29.6, 29.77, 29.83, 29.85, 29.89, 30.3, 32.1, 42.7, 75.3, 121.3, 127.7, 128.1, 128.6, 137.8, 145.2, 146.1, 147.7 and 158.7; mass spectrum (APCI), m/z 481.4157 (M+H)+ C32H53N2O requires 481.4158). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 23% 2: 40% | Stage #1: 2-(azetidin-1-yl)-5-(benzyloxy)-3,4,6-trimethylpyridine With n-butyllithium; potassium <i>tert</i>-butylate In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: pentadecyl bromide In tetrahydrofuran; hexane at 0℃; for 0.5h; | 4.1.15 2-(Azetidin-1-yl)-5-(benzyloxy)-6-hexadecyl-3,4-dimethylpyridine (19) and 2-(Azetidin-1-yl)-5-(benzyloxy)-4-hexadecyl-3,6-dimethylpyridine (20) To a stirred solution containing 109 mg (0.38mmol) of 18 and 65.0 mg (0.57 mmol) of KOtBu in 6 mL of anhyd THF at -78°C was added 228 μL (0.57mmol) of a 2.5M solution of n-BuLi in hexane. The reaction mixture was stirred at -78°C for 30 min and then 165 μL (0.57mmol) of 1-bromopentadecane was added dropwise. The reaction mixture was stirred at 0°C for an additional 30 min, quenched with satd aq ammonium chloride and then extracted with 100mL of EtOAc. The combined organic phase was washed with brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a column of silica gel (30×2cm). Elution with hexane followed by 96:4 hexane/Et2O afforded 19 and 20 as yellowish oils: yields 43mg (23%) and 74mg (40%), respectively; silica gel TLC Rf 0.50 (3:2 hexane/Et2O) and Rf 0.38 (3:2 hexane/Et2O); (19) 1H NMR (CDCl3) δ 0.90 (t, 3H, J=7.2Hz), 1.23-1.37 (br m, 26H), 1.76 (quint, 2H, J=7.6Hz), 2.06 (s, 3H), 2.19 (s, 3H), 2.27 (quint, 2H, J=7.6Hz), 2.73 (t, 2H, J=8Hz), 4.05 (t, 4H, J=7.6Hz), 4.72 (s, 2H) and 7.32-7.50 (m, 5H); 13C NMR (CDCl3) δ 12.9, 14.1, 14.3, 17.1, 22.8, 28.9, 29.5, 29.81, 29.87, 29.9, 32.08, 32.1, 52.7, 75.5, 116.4, 127.9, 128.1, 128.6, 137.8, 139.8, 145.7, 149.5 and 156.8; mass spectrum (APCI), m/z (M+H)+ 493.4159 (C33H53N2O requires 493.4158); (20) 1H NMR (CDCl3) δ 0.89 (t, 3H, J=7.2Hz), 1.24-1.34 (br m, 26H), 1.48 (quint, 2H, J=7.6Hz), 2.07 (s, 3H), 2.27 (quint, 2H, J=7.6Hz), 2.44 (s, 3H), 2.61 (t, 2H, J=8.0Hz), 4.05 (t, 4H, J=7.2Hz), 4.75 (s, 2H) and 7.33-7.50 (m, 5H); 13C NMR (CDCl3) δ 13.9, 14.3, 17.0, 19.5, 22.9, 27.1, 29.53, 29.57, 29.76, 29.82, 29.83, 29.87, 30.3, 32.1, 52.7, 75.4, 116.2, 127.7, 128.0, 128.7, 137.9, 144.7, 145.85, 145.91 and 157.1; mass spectrum (APCI), m/z (M+H)+ 493.4149 (C33H53N2O requires 493.4158). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triphenylphosphine In diethyl ether | Pentadecyltriphenylphosphonium bromide Pentadecyltriphenylphosphonium bromide A solution of 1-bromopentadecane (30.0 g, 103 mmol) and triphenylphosphine (27.02 g, 103 mmol) in MeCN (200 mL) was refluxed at 80 °C for five days. After removal of the solvent in vacuo, Et2O (30 mL) was added and the resulting white precipitate was filtered off, washed with Et2O and dried on high vacuum for 24 h to give pentadecyltriphenylphosphonium bromide (49.66 g, 87%) as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran at -40 - -10℃; | General procedure for the synthesisof compounds 5-16 and analytical data General procedure: To a solution of tetramethoxybenzene 3 (0.2 g, 0.989 mmol, 1 eq) and HMPA (0.1 eq) in THF (8 mL) was added n-BuLi (1 eq) at -40 °C. The reaction was warmed to -10 °C and stirred at this temperature for one hour. The alkyl halide 4a-4l (1.1 eq) were added dropwise, and the reaction was stirred overnight. Saturated NH4Cl was added to the reaction, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined and dried over MgSO4. Removal of the organic solvent under reduced pressure afforded crude mixture that was purified through flash chromatography eluting with hexane/ethyl acetate 85:15. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.5% | Stage #1: 1α,2β,3β-trihydroxy-urs-12-en-28-oic acid With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: pentadecyl bromide In N,N-dimethyl-formamide at 20℃; | 4.7 General procedure for preparation of alkyl ester derivatives (15-36) from compounds 12 or 14 General procedure: To a solution of the polyhydroxyl triterpene acids (12 or 14, 1.0 equiv) in dry DMF was added potassium carbonate (5.0 equiv). After stirring at room temperature for 30min, alkyl halide (1.2 equiv) was added and the mixture was stirred at room temperature until the starting material was not observed by TLC. The mixture was poured into water (30mL) and HCl (1.0M) was added to adjust pH-7 to quench reaction, then extracted with EtOAc (3×100mL). The organic phase was washed with saturated aqueous NaHCO3 and brine. Combined organic phases were dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by silica gel column chromatography with petroleum ether-acetone to afford the target compounds (15-36). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.1% | Stage #1: 1α,2β,3β-trihydroxy-olean-12-en-28-oic acid With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: pentadecyl bromide In N,N-dimethyl-formamide at 20℃; | 4.7 General procedure for preparation of alkyl ester derivatives (15-36) from compounds 12 or 14 General procedure: To a solution of the polyhydroxyl triterpene acids (12 or 14, 1.0 equiv) in dry DMF was added potassium carbonate (5.0 equiv). After stirring at room temperature for 30min, alkyl halide (1.2 equiv) was added and the mixture was stirred at room temperature until the starting material was not observed by TLC. The mixture was poured into water (30mL) and HCl (1.0M) was added to adjust pH-7 to quench reaction, then extracted with EtOAc (3×100mL). The organic phase was washed with saturated aqueous NaHCO3 and brine. Combined organic phases were dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by silica gel column chromatography with petroleum ether-acetone to afford the target compounds (15-36). |
Tags: 629-72-1 synthesis path| 629-72-1 SDS| 629-72-1 COA| 629-72-1 purity| 629-72-1 application| 629-72-1 NMR| 629-72-1 COA| 629-72-1 structure
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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.
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