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CAS No. : | 10401-11-3 | MDL No. : | MFCD00078347 |
Formula : | C8H6O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AODMJIOEGCBUQL-UHFFFAOYSA-N |
M.W : | 118.13 | Pubchem ID : | 139144 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 36.4 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.71 cm/s |
Log Po/w (iLOGP) : | 1.65 |
Log Po/w (XLOGP3) : | 1.84 |
Log Po/w (WLOGP) : | 1.45 |
Log Po/w (MLOGP) : | 2.05 |
Log Po/w (SILICOS-IT) : | 1.99 |
Consensus Log Po/w : | 1.8 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.22 |
Solubility : | 0.704 mg/ml ; 0.00596 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.89 |
Solubility : | 1.54 mg/ml ; 0.013 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.85 |
Solubility : | 1.66 mg/ml ; 0.014 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.23 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280 | UN#: | N/A |
Hazard Statements: | H302-H332 | 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 |
---|---|---|
71% | at 95℃; for 24 h; Schlenk technique | General procedure: Ferric sulfate hydrate (I, 8 molpercent), glacial acetic acid (5 mL) and the alkyne (1 - 2 mmol) were introducedinto a 50 mL Schlenk tube, equipped with an air condenser, and the mixture kept under stirring at 95 °C or120 °C, until consumption of the substrate or no further conversion, as evidenced by TLC or GC. Uponcooling, the supernatant solution was poored into water and the residue washed twice with diethyl ether.After extraction with diethyl ether ( 2), the combined organic layers were washed with a saturated aqueoussolution of sodium bicarbonate and then water until neutrality. Alternatively, the crude from the reactions ofsubstrates featuring hydroxyl or carbonyl groups, as for 12, 15, 20 and 22, was obtained by removing aceticacid under vacuum, in order to reduce loss of material during biphasic extraction. The products were purified |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: With potassium hydroxide In tetrahydrofuran; methanol; water for 2 h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water |
This compound was diluted with THF (6 mL) and MeOH (6 mL), and 10percent aqueous KOH (6 mL) was added. After stirring for 2 hr, the reaction mixture was neutralized by 1 N HCl and evaporated, extracted with CH2Cl2, and dried (Na2SO4). Column chromatography (n-hexane/acetone 5:1) yielded 3-ethynylphenol (162.8 mg, 70percent) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 14h; | [0276] 3-Ethynyl-phenol (4.0 g, 33.9 mmol), tert-butyldimethylsilyl chloride (5.62 g, 37.3 mmol) and imidazole (2.88 g, 42.4 mmol) were combined and diluted with DMF (25 mL). This was stirred at room temperature for 14h. Reaction contents were then poured onto water and extracted with EtOAc (3 x 100 mL). Organic phase was evaporated to provide desired product as an amber oil (7.9g, 98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With copper(l) iodide; triethylamine at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With copper(II) sulfate; sodium L-ascorbate; In ethanol; water; at 120℃; for 0.166667h;Microwave irradiation; | 3-Benzyloxy- 15-[3-(4-m-hydroxyphenyl-[1 , 2, 3]triazol- 1 -yl)-propyl]- 13-methyl-6, 7,8,9, 11, 12, 13, 14, 15, 16-decahydro-cyclopenta[a]phenanthren-17-one ethylene glycol acetal (XXVII-Ia-I)Azide (XXVI-Ia) (1.4 mmol), <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (2 eq.), L-ascorbic acid sodium salt (0.1 eq.) and CuSO4.5 H2O (0.01 eq.) are heated in a microwave in a 2:1 wate?EtOH mixture (8 ml.) at 12O0C for 10 min. The reaction mixture is transferred to a flask with MeOH and the alcohols are removed by evaporation. Water (30 ml.) is added and the mixture is extrated with EtOAc (3x 50 ml_). The combined organic layers are washed with brine (50 ml.) dried over Na2SO4 and concentrated to give 948 mg crude (XXVII-Ia-I) as an orange oil. This is purified by automated column chromatrography (Rf = 0.27 with DCM w. 2.5% MeOH) to give (XXVII-Ia-I) (43%) as a white foam. |
43% | With sodium L-ascorbate;copper(II) sulfate; In ethanol; water; at 120℃; for 0.166667h;Irradiation; | 3-Benzyloxy-15-[3-(4-m-hydroxyphenyl-[1,2,3]triazol-1-yl)-propyl]-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one ethylene glycol acetal (XXVII-Ia-I)Azide (XXVI-Ia) (1.4 mmol), <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (2 eq.), L-ascorbic acid sodium salt (0.1 eq.) and CuSO4.5H2O (0.01 eq.) are heated in a microwave in a 2:1 water:EtOH mixture (8 mL) at 120 C. for 10 min. The reaction mixture is transferred to a flask with MeOH and the alcohols are removed by evaporation. Water (30 mL) is added and the mixture is extrated with EtOAc (3×50 mL). The combined organic layers are washed with brine (50 mL) dried over Na2SO4 and concentrated to give 948 mg crude (XXVII-Ia-I) as an orange oil. This is purified by automated column chromatrography (Rf=0.27 with DCM w. 2.5% MeOH) to give (XXVII-Ia-I) (43%) as a white foam |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With copper(l) iodide; N-ethyl-N,N-diisopropylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; for 6h; | To a 10 mL round bottom was added isoxazolidine 22 (50 mg), dichlorobis(triphenylphosphine)palladium (30 mg), copper iodide (10 mg) and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (30 mg). The flask was flushed with argon and then DMF was added (2 mL) followed by diisopropylethylamine (70 muL). The reaction was stirred for 6 h and then diluted with ethyl acetate (50 mL), washed with 1 N HCl (50 mL) and brine (50 mL). The organic layer was dried with sodium sulfate and concentrated in vacuo. The title compound was purified by preparative TLC (1000 microns, silica) by elution with 3:1 ethyl acetate/hexanes to yield 48 mg (98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; at 20 - 55℃; for 4h; | Example 21 provides a method of synthesizing compounds 66-71. 70 71A mixture of compound 22 (46 mg), PdCI2(PPh3)2 (7 mg), and CuI (2 mg) in Et3N (6 ml_) was thrice degassed and exchanged with Ar followed by addition of 3-butyn-2-ol (16 mul_) at room temperature (rt) and stirred at 540C for 5 h and filtered. The filtrate was concentrated under reduced pressure and the residue separated employing flash chromatography on silica gel using as eluent 100:80 Hexanes/EtOAc to yield 12 mg of compound 66. A mixture of compound 22 (46 mg), PdCI2(PPh3)2 (7 mg), and CuI (2 mg) in Et3N (6 mL) was thrice degassed and exchanged with propyne. Propyne contained in a balloon was kept in contact with the reaction mixture by using a long syringe, the system was stirred at 450C overnight and filtered. The filtrate was concentrated under reduced pressure and the residue was separated employing flash chromatography on silica gel using as eluent 100:40 Hexanes/EtOAc to yield 22 mg of compound 67.A mixture of compound 22 (23 mg), PdCI2(PPh3)2 (3.5 mg), and CuI (1 mg) in Et3N (2 mL) was thrice degassed and exchanged with Ar followed by addition of 2-ethynyl pyridine (11 muL) at rt, stirred at 550C for 3 hr and filtered. EPO <DP n="109"/>The filtrate was concentrated under reduced pressure and the residue was separated employing flash chromatography on silica gel using as eluent 100:70 (v/v) Hexanes/EtOAc to yield 7 mg of compound 68.A mixture of compound 22 (34.5 mg), PdCI2(PPh3)2 (5.2 mg), and CuI (1.5 mg) in Et3N (5 ml_) was thrice degassed and exchanged with Ar followed by addition of 3-ethynyl phenol (16 mg) at rt and stirred at 550C for 4 hr and filtered. The filtrate was concentrated under reduced pressure and the residue was separated employing flash chromatography on silica gel using as eluent 100:60 (v/v) Hexanes/EtOAc to yield 20 mg of compound 69. A mixture of compound 22 (46 mg), PdCI2(PPh3)2 (7 mg), and CuI (2 mg) in Et3N (3 ml.) was thrice degassed and exchanged with Ar followed by addition of R(+)3-butyn-2-ol (16 muL) at rt and stirred at 550C for 4 hr and filtered. The filtrate was concentrated under reduced pressure and the residue was separated employing flash chromatography on silica gel using as eluent 100:65 Hexanes/EtOAc to yield compound 70. Compound 71 was synthesized similarly as compound 70 after substituting R(+)3-butyn-2-ol with S(-)3-butyn-2-ol. EPO <DP n="110"/> |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With caesium carbonate; sodium iodide; In acetone; at 20℃;Heating / reflux; | EXAMPLE 68 Preparation of 1-(cyclopropylmethoxy)-3-ethynylbenzene To a solution of <strong>[10401-11-3]3-ethynylphenol</strong> (1.18 g, 10.0 mmol) in acetone (30 mL) is added (bromomethyl)cyclopropane (1.02 mL, 10.0 mmol), sodium iodide (0.75 g, 5.0 mmol) and Cs2CO3 (6.52 g, 20.0 mmol) at room temperature. After refluxing over night, the reaction mixture is cooled, diluted with Et2O (300 mL) and pass through a thin layer of silica gel. The solution is concentrated. The resultant residue is purified by chromatography (silica gel, EtOAc/hexane: 1/99) to give the title compound (1.45 g, 84%) as an oil. MS(+) APPI: 173 (M+H)+. |
84% | With caesium carbonate; sodium iodide; In acetone; at 20℃; | EXAMPLE 61; Preparation of 1-(cyclopropylmethoxy)-3-ethynylbenzene; To a solution of <strong>[10401-11-3]3-ethynylphenol</strong> (1.18 g, 10.0 mmol) in acetone (30 mL) is added (bromomethyl)cyclopropane (1.02 mL, 10.0 mmol), sodium iodide (0.75 g, 5.0 mmol) and Cs2CO3 (6.52 g, 20.0 mmol) at room temperature. After refluxing over night, the reaction mixture is cooled, diluted with Et2O (300 mL) and pass through a thin layer of silica gel. The solution is concentrated. The crude material is purified by chromatography (silica gel, EtOAc/hexane: 1/99) to give the title compound (1.45 g, 84%) as an oil. MS(+) APPI: 173 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate; In acetonitrile; at 20℃; for 24h; | EXAMPLE 56; Preparation of 3-benzyloxy-1-ethynylbenzene; A mixture of 3-hydroxy-1-ethynylbenzene (4.36 g, 37 mmol), benzylbromide (6.95 g, 4.1 mmol) and K2CO3 (10.2 g, 7.4 mmol) in acetanitrile (50 ml) is stirred at room temperature for 24 hr. The insoluble material is removed by filtration and filtrate is concentrated. The crude material is purified by flash chromatography (silica gel, hexane/EtOAc: 95/5) to afford the title compound as a clear oil 5.2 g (68%). 1HNMR (400 MHz, CDCl3): delta (ppm) 3.05 (s, 1H), 5.05 (s, 2H), 6.98 (d, 1H) 7.00-7.50 (m, 8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In acetone; at 110℃; for 0.75h;Microwave irradiation;Product distribution / selectivity; | 3-(2-methoxyethoxy)phenylacetylene; 3-Hydroxyphenylacetylene (237mg, 2mmol) was heated with 2- bromoethylmethylether (0.23mL, 2.4mmol) and potassium carbonate (322mg, 2.4mmol) in acetone (5mL) to 110 0C in a microwave oven (CEM Discover) for 45 minutes. Water (ImL) was added to the mixture and the whole was extracted with dichloromethane (2x25mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to afford a brown oil. The oil was purified by EPO <DP n="21"/>column chromatography (SiO2, dichloromethane) to afford 3-(2- methoxyethoxy)phenylacetylene as a colourless oil (247mg, 70% yield). 1H-NMR (400 MHz; CDCl3): 7.23 (IH, dd, / 8.8, 8.0), 7.08 (IH, dt, / 7.6, 1.2), 7.04 (IH, dd, / 1.48, 2.7), 6.94 (IH, ddd, / 1.0, 2.6, 8.3), 4.11 (2H, t, J 4.6), 3.74 (2H, t, / 4.6), 3.45 (3H, s), 3.05 (IH, s). |
70% | With potassium carbonate; In acetone; at 110℃; for 0.75h;Microwave irradiation; | 3-Hydroxyphenylacetylene (237 mg, 2 mmol) was heated with 2-bromoethylmethylether (0.23 mL, 2.4 mmol) and potassium carbonate (322 mg, 2.4 mmol) in acetone (5 mL) to 110 C. in a microwave oven (CEM Discover) for 45 minutes. Water (1 mL) was added to the mixture and the whole was extracted with dichloromethane (2*25 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to afford a brown oil. The oil was purified by column chromatography (SiO2, dichloromethane) to afford 3-(2-methoxyethoxy)phenylacetylene as a colourless oil (247 mg, 70% yield). 1H-NMR (400 MHz; CDCl3): delta=7.23 (1H, dd, J 8.8, 8.0), 7.08 (1H, dt, J 7.6, 1.2), 7.04 (1H, dd, J1.48, 2.7), 6.94 (1H, ddd, J1.0, 2.6, 8.3), 4.11 (2H, t, J 4.6), 3.74 (2H, t, J 4.6), 3.45 (3H, s), 3.05 (1H, s). |
70% | With potassium carbonate; In acetone; at 110℃; for 0.75h;Microwave irradiation; | 3-(2-methoxyethoxy)phenylacetylene; 3-Hydroxyphenylacetylene (237 mg, 2 mmol) was heated with 2-bromoethylmethylether (0.23 mL, 2.4 mmol) and potassium carbonate (322 mg, 2.4 mmol) in acetone (5 mL) to 110 C. in a microwave oven (CEM Discover) for 45 minutes. Water (1 mL) was added to the mixture and the whole was extracted with dichloromethane (2×25 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to afford a brown oil. The oil was purified by column chromatography (SiO2, dichloromethane) to afford 3-(2-methoxyethoxy)phenylacetylene as a colourless oil (247 mg, 70% yield). 1H-NMR (400 MHz; CDCl3): delta=7.23 (1H, dd, J 8.8, 8.0), 7.08 (1H, dt, J 7.6, 1.2), 7.04 (1H, dd, J 1.48, 2.7), 6.94 (1H, ddd, J 1.0, 2.6, 8.3), 4.11 (2H, t, J 4.6), 3.74 (2H, t, J 4.6), 3.45 (3H, s), 3.05 (1H, s). |
67% | With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 12h; | Dissolve <strong>[10401-11-3]3-ethynylphenol</strong> (300mg, 2.53mmol) in DMF (25mL), then add anhydrous potassium carbonate (702mg, 5.07mmol) and 2-bromoethyl methyl ether (0.44mL, 4.57mmol, 1.1g / mL), heated to 85 for 12h.The reaction was stopped, the solvent was concentrated, water (60 mL) was added, and ethyl acetate was extracted (50 mL × 3).The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE / EtOAc (v / v) = 24/1) to obtain 300 mg of colorless liquid, yield: 67%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 20℃; for 3h;Product distribution / selectivity; | Step 1) 3-((4-(difluoromethoxy)phenyl)ethynyl)phenol A mixture of <strong>[128140-82-9]1-(difluoromethoxy)-4-iodobenzene</strong> (0.300 g, 1.11 mmol), 3-ethynylphenol (0.252 g, 1.39 mmol), bis(triphenylphosphino)palladium(II) chloride (0.039 g, 55 mumol), copper(I) iodide (0.006 g, 32 mumol) and triethylamine (0.62 g, 6.11 mmol) in DMF (4 mL) was stirred at RT for 3 h. The solvent is removed and the material is absorbed onto celite and purified by flash chromatography (silica, 5:95 ethyl acetate/hexanes) to afford 1-3-((4-(difluoromethoxy)phenyl)ethynyl)phenol (0.25 g, 86%) as an off white solid. Step a) 3-((4-(Difluoromethoxy)phenyl)ethynyl)phenolA solution of 4-(difluoromethoxy)phenyl iodide (4.70 g) in deoxygenated dimethylformamide was treated with trans-dichlorobis(triphenylphosphine) palladium(II) (244 mg) and copper(II) iodide 66 mg) followed by triethylamine (7.52 mL), stirred under a nitrogen atmosphere for 5 min., treated with 3-hydroxyphenyl acetylene (2.467 g), stirred under nitrogen atmosphere for 16 h, poured into ethyl acetate and was washed with 0.05 N HCl and water. The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was chromatographed, silica gel, 40% ethyl acetate/hexane as eluent, to afford 3-((4-(difluoromethoxy)phenyl)ethynyl)phenol as a tan solid, 5.40 g; 1H NMR (DMSO-d6): d 9.64 (s, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.27 (t, J=73.7 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.16 (m, 1H), 6.94 (m, 1H), 6.86 (m, 1H), and 6.77 (m, 1H); MS (ES neg) m/z 260. |
With copper(l) iodide; triethylamine;trans-bis(triphenylphosphine)palladium dichloride; In N,N-dimethyl-formamide; for 16h; | Step a) 3-((4-(Difluoromethoxy)phenyl)ethynyl)phenol A solution of 4-(difluoromethoxy)phenyl iodide (4.70 g) in deoxygenated dimethylformamide was treated with trans-dichlorobis(triphenylphosphine) palladium(II) (244 mg) and copper(II) iodide 66 mg) followed by triethylamine (7.52 mL), stirred under a nitrogen atmosphere for 5min., treated with 3-hydroxyphenyl acetylene (2.467 g), stirred under nitrogen atmosphere for 16 h, poured into ethyl acetate and was washed with 0.05 N HCl and water. The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was chromatographed, silica gel, 40% ethyl acetate/hexane as eluent, to afford 3-((4-(difluoromethoxy)phenyl)ethynyl)phenol as a tan solid, 5.40 g; 1H NMR (DMSO-d6): delta 9.64 (s, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.27 (t, J=73.7 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.16 (m, 1H), 6.94 (m, 1H), 6.86 (m, 1H), and 6.77 (m, 1H); MS (ES neg) m/z 260. | |
With copper(l) iodide; triethylamine;trans-bis(triphenylphosphine)palladium dichloride; In N,N-dimethyl-formamide; for 16h;Product distribution / selectivity; | Step a) 3-((4-(Difluoromethoxy)phenyl)ethynyl)phenol A solution of 4-(difluoromethoxy)phenyl iodide (4.70 g) in deoxygenated dimethylformamide was treated with trans-dichlorobis(triphenylphosphine) palladium(II) (244 mg) and copper(II) iodide 66 mg) followed by triethylamine (7.52 mL), stirred under a nitrogen atmosphere for 5 min., treated with 3-hydroxyphenyl acetylene (2.467 g), stirred under nitrogen atmosphere for 16 h, poured into ethyl acetate and was washed with 0.05 N HCl and water. The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was chromatographed, silica gel, 40% ethyl acetate/hexane as eluent, to afford 3-((4-(difluoromethoxy)phenyl)ethynyl)phenol as a tan solid, 5.40 g; 1H NMR (DMSO-d6): delta 9.64 (s, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.27 (t, J=73.7 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.16 (m, 1H), 6.94 (m, 1H), 6.86 (m, 1H), and 6.77 (m, 1H); MS (ES neg) m/z 260. EXAMPLE 81Preparation of 2-Amino-5-[4-(difluoromethoxy)phenyl]-5-(3hydroxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one Step a) 3-((4-(Difluoromethoxy)phenyl)ethynyl)phenolA solution of 4-(difluoromethoxy)phenyl iodide (4.70 g) in deoxygenated dimethylformamide was treated with trans-dichlorobis(triphenylphosphine) palladium(II) (244 mg) and copper(II) iodide 66 mg) followed by triethylamine (7.52 mL), stirred under a nitrogen atmosphere for 5 min., treated with 3-hydroxyphenyl acetylene (2.467 g), stirred under nitrogen atmosphere for 16 h, poured into ethyl acetate and was washed with 0.05 N HCl and water. The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was chromatographed, silica gel, 40% ethyl acetate/hexane as eluent, to afford 3-((4-(difluoromethoxy)phenyl)ethynyl)phenol as a tan solid, 5.40 g; 1H NMR (DMSO-d6): delta 9.64 (s, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.27 (t, J=73.7 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.16 (m, 1H), 6.94 (m, 1H), 6.86 (m, 1H), and 6.77 (m, 1H); MS (ES neg) m/z 260. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With cesium fluoride; In acetonitrile; for 48h; | 3-Hydroxyphenylacetylene (0.2 g, 1.7 mmol), 3-methoxy-2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.54 g, 1.65 mmol; described in: Pena, D.; Perez, D.; Guitian, E.; Castedo, L. J. Am. Chem. Soc. 1999, 121, 5827-5828) and cesium fluoride (0.78 g, 5.1 mmol) in acetonitrile (25 mL) was stirred for 48 h. The solvent was removed in vacuo and the resulting residue was dissolved in ethyl acetate and washed with saturated aqueous sodium carbonate, water and brine. The organic phase was dried over sodium sulfate and concentrated to give 0.32 g (87% yield) of the title compound: 1H NMR (DMSO-J6) delta 7.39 (t, J= 7.91 Hz, 1 H), 7.31 (t, J= 8.16 Hz, 1 H), 7.23 - 7.25 (m, 1 H), 7.03 - 7.08 (m, 2 H), 6.75 - 6.78 (m, 1 H)5 6.62 (t, J= 2.38 Hz, 1 H) 6.56 - 6.59 (m, 1 H), 4.23 (s, IH), 3.74 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 65℃; for 1h; | B) 3-Ethynylphenol (1.18 g, 10 mmol), 2-chloro-N,N-dimethylethanamine (1.44 g, 10 mmol), Cesium carbonate (7.0 g, 21 mmol) was dissolved in dimethyl formamide (20 mL) and the mixture was heated to 65 0C for 1 h. The mixture was cooled to RT and the partitioned between water and dichloromethane. The organic layer was separated, washed with 2nu NaOH and then extracted with IN HCl. The <n="39"/>HCl solution was then neutralized with aqueous NaOH and extracted with dichloromethane. The organic layer was dried and concentrated to afford 2-(3- ethynylphenoxy)-N,N-dimethylethanamine (0.6 g) as an oil. LC/MS; (M+H)+ = 190. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In ethyl acetate; at 20 - 70℃; for 54.7h; | Step 2(S)-2-amino-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamideTo a degassed solution containing (S)-2-amino-5-bromo-N-[methyl(oxo)phenyl-lambda6- sulfanylidene]nicotinamide (106 mg, 0.3 mmol) and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (50 mg, 0.42 mmol) in 2.0 mL EtOAc at room temperature was added triethylamine (0.13 mL, 0.9 mmol), dichlorobis(triphenylphosphine)palladium(II) (21 mg, 0.03 mmol), and copper(I)iodide (6 mg, 0.03 mmol). The reaction was stirred at 70 0C for 3.3 hours. Additional 3- hydroxyphenylacetylene was added (50 mg, 0.42 mmol) and then again at 5.3 hours (75 mg, 0.63 mmol). The reaction was cooled to room temperature, and after 23 hours additional dichlorobis(triphenylphosphine)palladium(II) (20 mg, 0.03 mmol) was added. The reaction was heated to 60 0C and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (120 mg, 1.0 mmol) in 0.7 mL EtOAc (degassed) added dropwise over 7 minutes. The heat was removed after 1 hour and the reaction stirred an additional 22 hours at room temperature. The reaction was dissolved in EtOAc and washed with H2O. The EtOAc layer was extracted with 2% aqueous HCl. The combined acidic aqueous layers were washed with 30% EtOAc/hexane and then made basic with Na2CO3. The basic aqueous layer was extracted with EtOAc. Then the combined organic layers washed with brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a white solid (5 mg, 4%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In N,N-dimethyl-formamide; at 60℃; for 0.833333h; | Step 5(S)-Ethyl [N-({5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}carbonyl)-S- phenylsulfonimidoyl] acetateA solution ethyl {N-[(5-bromopyridin-3-yl)carbonyl]-S-phenylsulfonimidoyl} acetate (216 mg, 0.52 mmol) and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (0.052 mL, 0.79 mmol) in anhydrous DMF (3 mL) was treated with triethylamine (0.22 mL, 1.58 mmol). The reaction mixture was degassed (alternating vacuum and argon) and PdCl2(Ph3P)2 (36.9 mg, 0.052 mmol) and triphenylphosphine (3.4 mg, 0.013 mmol) were added. The reaction mixture was degassed (alternating vacuum and argon) and placed under an atmosphere of 1 :3 Argon/hydrogen atmosphere. Copper( I+) iodide was added and the reaction mixture was heated at 60 0C for 50 min. The brown reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc. The organic layer was collected and washed further with saturated aqueous NaHCO3 (IX), brine (IX), and dried over anhydrous Na2SO4. The residue was purified by chromatography (silica gel, 50: 1 CHCl3 :MeOH). The product containing fractions were concentrated to give the title compound as a light yellow solid (220 mg, 94 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 20℃; for 5h; | Step 2 (R)-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamideTo a degassed solution of 2.0 mL DMF at room temperature containing (R)-5-bromo-N- [methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide (105 mg, 0.31mmol), 3- hydroxyphenylacetylene (73 mg, 0.62 mmol) and triethylamine (0.13 mL, 0.93mmol) was added <n="64"/>dichlorobis(triphenylphosphine)palladium(II) (22 mg, 0.031 mmol) and copper(I)iodide (3 mg, 0.016 mmol). The reaction was stirred at room temperature for 1.5 hours. Additional 3- hydroxyphenylacetylene was added (30 mg, 0.25 mmol) and the reaction was stirred at room temperature for an additional 3.5 hours. After proceeding for 5 hours the reaction was partitioned between EtOAc and H2O and the EtOAc layer washed with H2O, brine, dried with anhydrous Na2Stheta4 and concentrated. The residual dark oil was purified by chromatography (silica gel, CHCl3/EtOAc) and the product containing fractions were concentrated. The resulting solid was triturated with EtOAc/hexane to give the title compound as an off-white solid (37 mg, 32 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | copper(II) sulfate; sodium L-ascorbate; In water; tert-butyl alcohol; for 24h; | To a stirred solution of <strong>[10401-11-3]3-ethynylphenol</strong> (100 mg, 0.85 mmol) and benzylazide (115 mg, 0.86 mmol) in 1:1 tert-butanol: water (3 mL) was added sodium ascorbate (16.8 mg, 0.085 mmol), followed by CuSO45H2O (2.12 mg, 0.0085 mmol). (Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of Azides and Terminal Alkynes. Angew. Chem. Int. Ed. 2002, 41, 2596-2599.) The reaction mixture was stirred for 24 h, evaporated, extracted with CH2Cl2, and dried (Na2SO4). Column chromatography (n-hexane/ethyl acetate 2:1) yielded the desired product (120.0 mg, 0.48 mmol, 57%) as a white solid. N-methyl-3-(1-benzyl-1H-1,2,3-triazol-4-yl)phenyl carbamate: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With methanol; potassium hydroxide; In tetrahydrofuran; at 20℃; for 10h;Inert atmosphere; | 3-((trimethylsilyl) ethynyl) phenol (1.3g, 6.8mmol) was dissolved in a mixed solvent of methanol (20mL) and THF (20mL),Potassium hydroxide (0.46g, 8.2mmol) was added to the reaction solution. The nitrogen was replaced three times, and the reaction was stirred at room temperature for 10 hours under nitrogen protection.The reaction was stopped, concentrated, water (100 mL) was added, hydrochloric acid (4N) was used to adjust the pH to 6, and dichloromethane was extracted (50 mL × 3).Anhydrous sodium sulfate was dried, filtered, concentrated, and purified by silica gel column chromatography (PE / EtOAc (v / v) = 15/1) to obtain 710 mg of light yellow oil, yield: 88%. |
70% | This compound was diluted with THF (6 mL) and MeOH (6 mL), and 10% aqueous KOH (6 mL) was added. After stirring for 2 hr, the reaction mixture was neutralized by 1 N HCl and evaporated, extracted with CH2Cl2, and dried (Na2SO4). Column chromatography (n-hexane/acetone 5:1) yielded 3-ethynylphenol (162.8 mg, 70%) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; decafluorobiphenyl; recorcinol With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 24h; Under a nitrogen atmosphere; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 3h; | 11 EXAMPLE 11Preparation of a Polymer Having a Repeating Unit Represented by the Formula (Ab) and a Thermosettable Ethynyl Group as an End Group5.0 g (14.96 mmol) of decafluorobiphenyl, 1.8 g (6.8 mmol) of octafluoro-1,6-hexanediol and 0.7 g (6.8 mmol) of resorcinol are introduced into a 100 mL three-necked flask and dissolved thoroughly in 43 mL of a DMAc solvent. After 5.38 g of K2CO3 is added into the reaction flask, the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 24 hours. Then, 0.34 g (2.85 mmol) of 3-ethynylphenol is added into the flask and stirred for 3 hours at the same temperature. After that, the resulting reaction mixture is cooled and precipitated in a mixed solution of methanol/DI water. The resulting polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.7 (s), 5.16 (t), 7.02 (d), 7.17 (s), 7.3 (m), 7.48 (m). Mn=7,300, PDI=2.3, thermosetting temp. (Tc)=250 C., thermal decomposition temp. (Td)=405 C. By controlling a molar ratio of octafluoro-1,6-hexanediol to resorcinol, various copolymers can be obtained according to the same reaction conditions as described above. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; 4,4'-(hexafluoroisopropylidene)diphenol; decafluorobiphenyl With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 24h; Under a nitrogen atmosphere; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 4h; | 10 EXAMPLE 10Preparation of a Polymer Having a Repeat Unit Represented by the Formula (Aa) and a Thermosettable Ethynyl Group as an End Group5.0 g (14.96 mmol) of decafluorobiphenyl, 1.8 g (6.8 mmol) of octafluoro-1,6-hexanediol and 2.3 g (6.8 mmol) of 4,4'-hexafluoroisopropylidene)diphenol (6FBPA) are introduced into a 100 mL three-necked flask and dissolved thoroughly in 51 mL of a DMAc solvent. 5.26 g of K2CO3 is added into the reaction flask, and the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 24 hours. 0.34 g (2.85 mmol) of 3-ethynylphenol is added into the flask and then stirred for 4 hours at the same temperature. After that, the reaction mixture is cooled and precipitated in a mixed solution of methanol/DI water. The resulting polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.1 (s), 4.78 (t), 7.032 (d), 7.2 (m), 7.4 (d, 4H). Mn=37,800, PDI=2.1, thermal decomposition temp. (Td)=250 C. By controlling a molar ratio of octafluoro-1,6-hexanediol to 4,4'-hexafluoroisopropylidene)diphenol, various copolymers can be obtained according to the same reaction conditions as described above |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; decafluorobiphenyl; 9,9-bis(4-hydroxyphenyl)fluorene With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 24h; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 3h; | 12 EXAMPLE 12Preparation of a Polymer Having a Repeat Unit Represented by the Formula (Ac) and a Thermosettable Ethynyl Group as an End Group5.0 g (14.96 mmol) of decafluorobiphenyl, 1.8 g (6.8 mmol) of octafluoro-1,6-hexanediol and 2.4 g (6.8 mmol) of 4,4'-(9-fluorenylidene)diphenol are introduced into a 100 ml three-necked flask and dissolved thoroughly in 52 mL of a DMAc solvent. After 5.38 g of K2CO3 is added into the reaction flask, the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 24 hours. Then, 0.34 g (2.85 mmol) of 3-ethynylphenol is added into the flask and stirred for 3 hours at the same temperature. After that, the reaction mixture is cooled and precipitated in a mixed solution of methanol/DI water. The resulting polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.73 (s), 5.15 (t), 7.1 (d), 7.25 (d), 7.32 (m), 7.4 (m), 7.49 (d), 7.91 (d), Mn=7,100, PDI=2.3, thermosetting temp. (Tc)=250 C., thermal decomposition temp. (Td)=405 C. By controlling a molar ratio of octafluoro-1,6-hexanediol to 4,4'-(9-fluorenylidene)diphenol, various copolymers can be obtained according to the same reaction conditions as described above. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; decafluorobiphenyl With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 8h; Under a nitrogen atmosphere; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 16h; | 6 EXAMPLE 6Preparation of a Polymer Having a Repeat Unit Represented by the Formula (A) and a Thermosettable Ethynyl as an End Group5.0 g (14.965 mmol) of decafluorobiphenyl and 3.55 g (13.54 mmol) of octafluoro-1,6-hexanediol are introduced into a 100 mL three-necked flask and dissolved thoroughly in 48 mL of a DMAc solvent. 5.38 g of K2CO3 is added into the reaction flask, and the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 8 hours. 0.34 g (2.85 mmol) of 3-ethynyl phenol is then added into the flask and stirred for 16 hours at the same temperature. After that, the reaction temperature is cooled and precipitated in a mixed solution of methanol/DI water. The produced polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.7 (s), 5.15 (t), 7.3 (m), 7.4 (d). Mn=8,200, PDI=2.2, thermal decomposition temp. (Td)=400 C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; bis(pentafluorophenyl)-methanone With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 48h; Under a nitrogen atmosphere; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 4h; | 7 EXAMPLE 7Preparation of a Polymer Having a Repeat Unit Represented by the Formula (C) and a Thermosettable Ethynyl Group as an End Group5.0 g (13.8 mmol) of decafluorobenzophenone and 3.55 g (12.5 mmol) of octafluoro-1,6-hexanediol are introduced into a 100 mL three-necked flask and dissolved thoroughly in 47 mL of a DMAc solvent. 5.0 g of K2CO3 is added into the reaction flask, and the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 48 hours. 0.31 g (2.6 mmol) of 3-ethynylphenol is then added into the flask and stirred for 4 hours at the same temperature. After that, the reaction mixture is cooled and precipitated in a mixed solution of methanol/DI water. The produced polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.6 (s), 5.1 (t), 7.3 (m), 7.4 (d). Mn=5,200, PDI=2.0, thermal decomposition temp (Td)=380 C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: Hexafluorobenzene; 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol; 9,9-bis(4-hydroxyphenyl)fluorene With potassium carbonate In N,N-dimethyl acetamide at 80℃; for 24h; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 80℃; for 3h; | 13 EXAMPLE 13Preparation of a Polymer Having a Repeat Unit Represented by the Formula (Da) and a Thermosettable Ethynyl Group as an End Group5.0 g (26.87 mmol) of hexafluorobenzene, 3.2 g (12.2 mmol) of octafluoro-1,6-hexanediol and 4.1 g (12.2 mmol) of 4,4'-(9-fluorenylidene)diphenol are introduced into a 100 mL three-necked flask and dissolved thoroughly in 70 mL of a DMAc solvent. After 9.6 g of K2CO3 is added into the reaction flask, the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 24 hours. Then, 0.6 g (5.1 mmol) of 3-ethynylphenol is added into the flask and stirred for 3 hours at the same temperature. After that, the reaction mixture is cooled and precipitated in a mixed solution of methanol/DI water. The resulting polymer is filtered and washed continuously with water. The obtained polymer is dried in a vacuum oven at 80 C. 1H-NMR (CDCl3): ? 3.7 (s), 4.94 (t), 7.1 (d), 7.2 (m), 7.41 (d). Mn=7,600, PDI=2.0, thermosetting temp. (Tc)=250 C., thermal decomposition temp. (Td)=405 C. By controlling a molar ratio of octafluoro-1,6-hexanediol to 4,4'-(9-fluorenylidene)diphenol, various copolymers can be obtained according to the same reaction conditions as described above. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: Hexafluorobenzene; 2,2,3,3,4,4,5,5-octafluoro-1,6-hexanediol With potassium carbonate In N,N-dimethyl acetamide at 80 - 120℃; for 72h; Under a nitrogen atmosphere; Stage #2: 3-hydroxy phenylacetylene In N,N-dimethyl acetamide at 120℃; for 4h; | 8 EXAMPLE 8Preparation of a Polymer Having a Repeat Unit Represented by the Formula (D) and a Thermosettable Ethynyl Group as an End Group5.0 g (26.9 mmol) of hexafluorobenzene and 6.4 g (24.3 mmol) of octafluoro-1,6-hexanediol are introduced into a 100 mL three-necked flask and dissolved thoroughly in 64 mL of a DMAc solvent. 10.0 g of K2CO3 is added into the reaction flask, and the resulting mixture is heated to 80 C. under a nitrogen atmosphere and stirred for 12 hours. Then, the reaction mixture is further heated up to 120 C. and left to react for 12 hours. 0.6 g (5.1 mmol) of 3-ethynylphenol is added into the flask and the resulting mixture is stirred for 4 hours at the same temperature. The reaction mixture is cooled, poured into DI water, and then extracted with ethyl ether. Very viscous liquid polymer is obtained. 1H-NMR (CDCl3): ? 3.8 (s), 5.3 (t), 7.3 (m), 7.4 (d). Mn=4,200, PDI=2.0, thermal decomposition temp (Td)=380 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 150℃; for 0.166667h;Inert atmosphere; Microwave irradiation; | To a solution of 3-bromo-N-(2-(ethyl(pyridin-2-yl)amino)ethyl)-N- methylbenzenesulfonamide (0.13 mmol) and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (0.19 mmol) in DMF (2 ml.) in a microwave vial was added copper iodide (0.026 mmol) and TEA (0.39 mmol). To the suspension was added Pd(PPh3)2CI2 (0.026 mmol). The vial was purged with N2, capped, and microwaved for 10 minutes at 1500C. The product was concentrated on a speedvac and purified via prep HPLC (Gilson with TFA additive) to produce 3-({3-[(4-pyridin-2-ylpiperazin-1- yl)sulfonyl]phenyl}ethynyl)phenol. LCMS Rt = 2.07 min (MS = 420). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 150℃; for 0.166667h;Inert atmosphere; Microwave irradiation; | To a solution of 1-(3-bromobenzyl)-4-(pyridin-2-yl)piperazine (0.15 mmol) and 3- hydroxyphenylacetylene (0.23 mmol) in DMF (2 ml.) was added copper iodide (0.03 mmol) and TEA (0.45 mmol). To the suspension was added Pd(PPh3)2Cl2 (0.03 mmol). The vial was purged with N2, capped, and microwaved for 10 minutes at 1500C. The reaction was concentrated on a speedvac and purified via prep HPLC (Gilson with TFA additive) producing 3-({3-[(4-pyridin-2- ylpiperazin-1-yl)methyl]phenyl}ethynyl)phenol. LCMS Rt = 1.84 min (MS = 370). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | (Example 12a) Compound (1)-11a was obtained in a similar manner to the synthesis in Example 10a, except that 3,5-diethynylaniline was used instead of 3-ethynylaniline. Synthesis of compound (1)-30a To a 500-ml three-neck flask, 10 g (0.050 mol) of 2.4-diaminophenol dihydrochloride, 200 ml of water and 21.0 g (0.15 mol) of pottasium carbonate were added in this order, and this mixture was stirred to dissolve the components. While cooling with ice, 22.3 g (0.10 mol) of di-t-butyl bicarbonate were dropped to the solution over 1.5 hours. After the completion of dropping, the temperature was raised to room temperature and the solution was allowed to react. After confirming the disappearance of the raw materials by HPLC, HCl was added to neutralize the solution, and intermediate compound 1 a was allowed to precipitate with an acid and collected by filtering. The obtained intermediate compound 1a was dissolved in NMP and 19.8 g (0.15 mol) of pyridine were added thereto. After dropping phenyl chlorocarbonate to the solution while cooling with ice, the temperature was raised to room temperatuer and the solution was allowed to react. After cofirming the dissapearance of the raw materials by HPLC, 11.8 g (0.10 mol) of 3-ethynylphenol was added thereto and heated to 50C. After confirming the disappearance of 3-ethynylphenol by HPLC, 96.1 g (1.0 mol) of methansulfonic acid were added while cooling with ice, and the solution was allowed to react. The obtained reaction solution was neutralized with sodium bicarbonate water, and 60 g of compound (1)-30a were allowed to crystallize with toluene (yield: 45%). The properties of the obtained compound were as follows. 1H-NMR (400 MHz, DMSO-d6): delta7.24 (s, 1H), 7.23 (d, 2H), 7.20 (t, 1H), 7.05 (d, 1H), 6.57 (d, 2H), 5.79 (d, 1H), 5.63 (s, 1H), 5.85 (s, 4H), 3.06 (s, 1H) MS: M+ = 268.08 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In acetonitrile; at 80℃; for 1.5h;Inert atmosphere; | 2-(2-Amino-5-iodo-pyrimidin-4-yl)-1-methyl-4-oxo-1 ,4,6,7-tetrahydro-pyrrolo[3,2-c]-pyridine-5-carboxylic acid tert-butyl ester (100 mg, 0.213 mmol) was suspended in dry acetonitrile (1.5 mL) in a dry screw cap Pirex tube. TEA (0.5 mL) was added and argon was bubbled through the mixture for 5 minutes. 3-Ethynylphenol (0.046 mL, 0.426 mmol, 2 eq) was then added followed by copper (I) iodide (2 mg, 0.11 mmol, 0.05 eq) and PdCI2(PPh3)2 (8 mg, 0.011 mmol, 0.05 eq). The tube was closed and the mixture was stirred at 800C for 1.5 hours. After cooling to RT the solid was filtered and washed with acetonitrile and ether. The solid was then washed on the filter with a 9:1 water/methanol mixture (2 mL) and dried under high vacuum at 500C for 2 hours. 50 mg of the desired product were obtained as beige solid(51%).HPLC (254 nm): R,: 6.07 min.1H-NMR (401 MHz, DMSO-de) delta = 9.65 (s, 1 H), 8.46 (s, 1 H), 7.51 (s, 1 H), 7.19 (t, J = 7.9 Hz, 1 H), 7.10 (s, 2 H), 6.89 (dt, J = 1.1, 7.7 Hz, 1 H), 6.77-6.83 (m, 2 H), 4.00 (t, J = 6.3 Hz, 2 H), 3.84 (s, 3 H), 2.99 (t, J = 6.3 Hz, 2 H),1.47 (s, 9 H).HRMS (ESI) calcd for C25H26N5O4 [M+H]+ 460.1980, found 460.1981. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In acetonitrile; at 20℃; for 4h;Inert atmosphere; | 2-[2-Amino-5-(3-hydroxy-phenylethynyl)-pyrimidin-4-yl]-1-(2-fluoro-ethyl)-4-oxo-1,4,6,7-tetrahydro- pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester [(ll)k , L2' = C?C, Q = Boc, R4 = 2-fluoroethyl] 2-(2-Amino-5-iodo-pyrimidin-4-yl)-1-(2-fluoro-ethyl)-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (95 mg, 0.190 mmol) was suspended in dry acetonitrile (2 mL) under nitrogen atmosphere. TEA (0.265 mL, 1.9 mmol, 10 eq) was added followed by <strong>[10401-11-3]3-ethynylphenol</strong> (0.041 mL, 0.380 mmol, 2 eq) and argon was bubbled through the mixture for 5 minutes. Copper (I) iodide (2 mg, 0.010 mmol, 0.05 eq) and PdCb(PPI^ (7 mg, 0.010 mmol, 0.05 eq) were then added and the mixture was stirred at room temperature for 4 hours. The solid was filtered and washed with acetonitrile (1 mL), a 9:1 water/methanol mixture (2 mL) and ether (2 mL) After drying under high vacuum at room temperature for 2 hours, 58 mg of the desired product were obtained as beige solid (62%). HPLC (254 nm): R1: 6.27 min.1H-NMR (401 MHz, DMSOd6) delta = 9.68 (s, 1 H), 8.47 (s, 1 H), 7.69 (s, 1 H), 7.21 (t, J = 7.9 Hz, 1 H), 7.11 (s, 2 H),6.93 (ddd, J = 1.0, 1.2, 7.7 Hz, 1 H), 6.77 - 6.85 (m, 2 H), 4.66 - 4.89 (m, 4 H), 4.00 (t, J = 6.2 Hz, 2 H), 3.00 (t, J =6.2 Hz, 2 H), 1.48 (s, 9 H).HRMS (ESI) calcd for C26H27FN5O4 [M+H]+ 492.2042, found 492.2035. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | (Table 6). Table 6. Cu-NHC (PI) catalyzed carboxylation of deactivated terminal alkynes with C02.Reaction conditions: alkynes (2.0 mmol), Cs2C03 (2.4 mmol), PI (5 mol %), C02 (1 atm), DMF (4 mL), r.t. General Procedure for Carboxylation of the Terminal Alkynes (lb as Example); CuCl (4.0 mg, 0.04 mmol, 2.0 mol %), TMEDA (3.5 mg, 0.03 mmol, 1.5 mol %), and K2C03 or Cs2C03 (2.4 mmol) were added to the DMF (4 mL) in the reaction tube (10 mL). C02 and 2 mmol of terminal alkynes (la, 204 mg) were introduced into the reaction mixture under stirring. The reaction mixture was stirred at room temperature (about 24 C) for 16 hours. After completion of the reaction, the reaction mixture was transferred to the potassium carbonate solution (2 N, 5 mL) and the mixture was stirred for 30 mins. The mixture was extracted with dichloromethane (3 >< 5 mL) and the aqueous layer was acidified with concentrated HC1 to PH = 1 , then extracted with diethyl ether (3 chi 5 mL) again. The combined organic layers were dried with anhydrous Na2S04, filtered and the solution was concentrated in vacuum affording pure product. Element analysis calcd (%) for lb [C9H602 (146.0)]: C 73.97, H 4.14; found: C 73.82, H 4.07. Data for 1H and 13C NMR of acids were all conducted in d - DMSO or CDC13 and consistent with the data in reported literatures. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With cobalt(II) chloride hexahydrate; 2-(2,6-diisopropylphenyliminomethyl)pyridine; zinc In tetrahydrofuran at 40℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With triethylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 120℃; for 3h; | Step 1: 3- [2-(3-Amino-6-bromo-pyrazin-2-yl)ethynyl] phenol[00151] 3-Ethynylphenol (560.5 mg, 310.9 mu^, 4.745 mmol) was added dropwise to a solution of 3,5-dibromopyrazin-2-amine (1 g, 3.954 mmol), triethylamine (4.001 g, 5.51 1 mL, 39.54 mmol), copper (I) iodide (90.37 mg, 0.4745 mmol) and Pd(PPh3)4 (228.5 mg, 0.1977 mmol) in DMF (10 mL) and the resulting solution heated at 120 C for 3 hours. The reaction mixture was cooled to ambient temperature and diluted with EtOAc andlMHCl/brine (1/1) and the layers separated. The aqueous layer was extracted with EtOAc (x 2) and the combined organic extracts washed with brine (x 2), dried (MgS04) and concentrated in vacuo . The residue was purified by column chromatography (ISCOCompanion, 120 g column, eluting with 0 to 40% EtO Ac/Petroleum Ether, dry loaded) to give the sub-title product as a yellow solid (815 mg, 71% Yield). XH NMR (400.0 MHz, DMSO) delta 6.88 (dd, IH), 7.00 (br s, 2H), 7.11 - 7.1 1 (m, IH), 7.17 (d, IH), 7.25 (t, IH), 8.12 (s, IH) and 9.77 (s, IH) ppm; MS (ES+) 292.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 1.5h;Sealed tube; | Step 3 : 3- [2- [3-Amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl] ethynyl] phenol[00144] 3-Ethynylphenol (187.0 mg, 103.7 mu,, 1.583 mmol) was added to a solution of 3- bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine (500 mg, 1.319 mmol), Et3N (1.335 g, 1.839 mL, 13.19 mmol), Copper(I) iodide (30.15 mg, 0.1583 mmol) and Pd(PPh3)4 (76.21 mg, 0.06595 mmol) in DMF (5 mL) and the resulting solution heated at 100 C for 90 minutes in a sealed tube. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and lMHCl/brine (1: 1). The layers were separated and the aqueous layer was extracted with ethyl acetate (x 2). The combined organics extracts were washed with brine, dried(MgS04) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 40 g column, eluting with 0 to 100%EtO Ac/Petroleum Ether) to give the title product as a yellow solid (352 mg, 68% Yield). XH NMR (400.0MHz, DMSO) delta 1.18 (d, 6H), 3.44 (sept, IH), 6.87 - 6.90 (m, IH), 7.13 - 7.15 (m, 3H), 7.19 - 7.21 (m, IH), 7.27 (t, IH), 7.90 (d, J = 8.6 Hz, 2H), 8.24 (d, J = 8.6 Hz, 2H), 8.75 (s, IH) and 9.77 (s, IH) ppm; MS (ES+) 394.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With copper(II) sulfate; sodium L-ascorbate; In water; tert-butyl alcohol; at 20℃; for 24h; | General procedure: A typical experimental procedure for the preparation of these compounds from the corresponding commercially available alkynes is described below. To a solution of alkyne (1.0 eq) with azide (1.2 eq) in tBuOH/H2O (1/1), were added CuSO4 (0.2 eq), AscNa (0.4 eq) at room temperature. The reaction mixture was stirred at rt for 24 h, then H2O was added and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure. The desired product was purified by flash chromatography (EtOAc/petroleum ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With copper(II) sulfate; sodium L-ascorbate; In water; N,N-dimethyl-formamide; at 100℃; for 0.5h; | Example 1616-chloro-8-((4-(3-hydroxyphenyl)-1 H-1 ,2,3-triazoM -yl)methyl)-2-oxo-1 ,2- dihydroquinoline-3-carboxylic acid[00386] To a mixture of 8-(azidomethyl)-6-chloro-2-oxo-1 ,2-dihydroquinoline-3- carboxylic acid (129a) (78 mg, 0.28 mmol) and <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (33.1 mg, 0.28 mmol, 1 .0 eq.) in DMF (1 .5 mL), Water (1 .5 mL) is added sodium L-ascorbate (5 mg, 10 mol%) and copper sulfate (3 mg, 5 mol%). The mixture is heated to 100 C for 30 minutes and then allowed to cool to room temperature. Water is added to the mixture and the orange suspension is filtered off. The residue is washed with water, EtOAc, DCM and diethyl ether to afford 32 mg (28%) of the product as a solid.1H NMR deltaEta (400 MHz; DMSO-d6): 6.04 (s, 2H), 6.68-6.78 (m, 1 H), 7.18-7.29 (m, 3H), 7.96 (s, 1 H), 8.23 (s, 1 H), 8.54 (s, 1 H), 8.94 (s, 1 H), 9.52 (s, 1 H), 12.78 (bs, 1 H), 14.39 (bs, 1 H).ESI-MS: 397/399 ([M+H]+, 100%, CI isotope pattern). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Example 812-((3-Hydroxyphenyl)ethynyl)-6,7-dihydroindolizin-8(5H)-one[00318]A mixture of 2-iodo-6,7-dihydroindolizin-8(5H)-one (200 mg, 0.766 mmol), 3- ethynylphenol (0.125 mL, 1 .149 mmol), TEA (427 muIota_, 3.06 mmol) and copper(l)iodide (7.30 mg, 0.038 mmol) in dry DMF (3 mL) is flushed with argon for 10 min. Pd(PPh3)2CI2 (16.13 mg, 0.023 mmol) is added, and the mixture is stirred at 60 C for 1 h. The reaction mixture is cooled to room temperature, poured into saturated aqueous NH4CI solution (25 mL) and extracted with EtOAc (2x20 mL). The combined organic layers are dried over Na2SO and concentrated in vacuo. Purification by column chromatography (silica, 50% EtOAc/heptane, isocratic), followed by recrystallization from /'-PrOH (~ 4 mL) and air-drying provides the title compound (123 mg, 64%) as a beige powder.1H NMR (DMSO-d6), deltaEta: 2.14-2.20 (m, 2H), 2.53 (t, 2H), 4.15 (t, 2H), 6.76-6.91 (m, 4H), 7.18 (t, 1 H), 7.50 (s, 1 H), 9.63 (br s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃; for 4.41667h;Inert atmosphere; Cooling with ice; | PI¾P (1.32 g, 5.04 mmol) in DCM (4 mL), under a nitrogen atmosphere, was cooled with an ice bath and treated with neat DIAD (397 mu?, 4.6 mmol). After 25 min the solution was added drop wise to 1 -methylpiperidin-4-ol hydrochloride (547 g, 4.6 mmol) and <strong>[10401-11-3]3-ethynylphenol</strong> (277 mu?, 4.2 mmol) in DCM (8 mL), cooled with an ice bath, under a nitrogen atmosphere, with stirring. The reaction was then stirred at room temperature 4 h. The volatiles were partially removed by evaporation and the residue was purified by flash chromatography (DCM/MeOH 95/5) affording the title compound as a colorless oil (360 mg, 39%). 1H NMR (400 MHz, DMSO-de) delta ppm 1.53 - 1.71 (m, 2 H) 1.90 (m, J=5.86 Hz, 2 H) 2.11 - 2.24 (m, 5 H) 2.60 (m, J=10.62 Hz, 2 H) 4.14 (s, 1 H) 4.31 - 4.44 (m, 1 H) 6.92 - 7.10 (m, 2 H) 7.21 - 7.33 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon monoxide; hydrogen; In tetrahydrofuran; at 70℃; under 7757.43 Torr; for 6h;Autoclave; | General procedure: To a 100 mL high-pressure reactor, phenylacetylene (1 mmol),Pd (0.96 mol%) in a 10 mL THF were transferred under an inertatmosphere. The reactor was flushed three times with nitrogen then pressurized with desired 150 psi of syngas, then heated at70C with constant stirring (400 rpm) for 6 h. After the comple-tion of reaction, the reactor cooled down to room temperature andthe remaining syngas was carefully depressurized. The resultantreaction mixture filtered off by simple filtration. The filtrate was then collected in sample vial and the product was extracted for fur-ther analysis such as GC, GC-MS,1H &13C NMR and matched with those of authentic data. Selective experiments were performed in triplicate and it was observed that results showed variation of ±2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 20℃; for 6h;Inert atmosphere; | General procedure: cis-1,2-dichloroethylene 6 (2.0 equiv.), terminal acetylenes(1.0 mmol, 1.0 equiv.), Pd(PPh3)4 (2.0 mol%), CuI (4.0mol%), n-butylamine (2.0 equiv.) and 4 mL diethyl ether were mixed together and stirred under nitrogen atmospherefor 6 h. Then the mixture was diluted with water and extracted with dichloromethane. The organic solvent was removed under vacuum and the residue was purified by flash column chromatography (n-hexane : ethyl acetate 10 : 1) to afford the corresponding (Z)-chloroenynes 6a-g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With piperidine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In diethyl ether; at 20℃; for 6h;Inert atmosphere; | General procedure: trans-1,2-dichloroethylene 7(2.0 equiv.), terminal acetylenes (1.0 mmol, 1.0 equiv.), PdCl2(PPh3)2 (2.0 mol%), CuI (4.0 mol%), piperidine (2.0 equiv.) and 4 mL diethyl ether were mixed together and stirred under nitrogen atmosphere for 6 h. Then the mixture was diluted with water and extracted with dichloromethane. The organic solvent was removed under vacuum and the residue was purified by flash column chromatography (n-hexane : ethyl acetate 10 : 1) to afford the corresponding (E)-chloroenynes 7a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In acetone; at 70℃; for 7h; | A mixture of 3-ethynyiphenol (3.31 g, 28.0 mmol), <strong>[683-57-8]2-bromoacetamide</strong> (2.36 g, 17.1 mmol) and K2C03 (5.53 g, 40.0 mmol) in acetone (50 mL) was stirred at 70 C for 7 h. The mixture was cooled to rt and filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE / EtOAc (V / V) = 1: 1) to give the title compound as a white solid (2.70 g, 90%). |
90% | With potassium carbonate; In acetone; at 70℃; for 7h; | A mixture of 3-ethynylphenol (3.31 g, 28.0 mmol), <strong>[683-57-8]2-bromoacetamide</strong> (2.36 g, 17.1 mmol) and K2CO3 (5.53 g, 40.0 mmol) in acetone (50 mL) was stirred at 70 C. for 7 h. The mixture was cooled to rt and filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as a white solid (2.70 g, 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71%; 6% | With iron(III) sulfate hydrate; at 95℃; for 24h;Schlenk technique; | General procedure: Ferric sulfate hydrate (I, 8 mol%), glacial acetic acid (5 mL) and the alkyne (1 - 2 mmol) were introducedinto a 50 mL Schlenk tube, equipped with an air condenser, and the mixture kept under stirring at 95 C or120 C, until consumption of the substrate or no further conversion, as evidenced by TLC or GC. Uponcooling, the supernatant solution was poored into water and the residue washed twice with diethyl ether.After extraction with diethyl ether ( 2), the combined organic layers were washed with a saturated aqueoussolution of sodium bicarbonate and then water until neutrality. Alternatively, the crude from the reactions ofsubstrates featuring hydroxyl or carbonyl groups, as for 12, 15, 20 and 22, was obtained by removing aceticacid under vacuum, in order to reduce loss of material during biphasic extraction. The products were purified |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1,2-dibromomethane; In N,N-dimethyl-aniline; at 120℃; for 12h;Inert atmosphere; Schlenk technique; | General procedure: Terminal alkynes(0.5 mmol), dibromomethane (2.5 mmol), N,N-dimethylaniline (1.5 mmol) wereplaced in a Schlenk tube (10 mL), and the mixture was stirred at 120 C for 12 h. Then, the mixture was cooledto room temperature, washed with saturated Na2CO3solution. The crude product was extracted with ethyl acetate three times. Theorganic layer was dried over anhydrous Na2SO4, andconcentrated under reduced pressure. The residue was purified by columnchromatography on silica gel and eluted with petroleum to afford the analyticallypure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With C15H14N4; caesium carbonate; triphenylphosphine; silver(I) chloride; In N,N-dimethyl-formamide; at 50℃; for 24h;Inert atmosphere; Schlenk technique; | General procedure: A mixture of 1 (0.5 mmol), B(OiPr)pin (0.75 mmol), PPh3+L1+AgCl (1 mol %), and Cs2CO3 (1.1 mmol) in DMF (5 mL) was stirred at 50C under Ar atmosphere for 24 h. The reaction mixture was acidified by 1 M solution of hydrochloric acid in an ice water bath, and the aqueous phase was extracted with ethyl acetate (three times). The combined organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography to give the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | Example 83: Synthesis of 2-amino-3-[2-(3- hydroxyphenyl)ethynyl]benzoic acid 2-amino-3-[2-(3-hydroxyphenyl)ethynyl]benzoic acid: To a sealed tube was loaded a mixture of 2-amino-3-bromo-benzoic acid methyl ester (50 mg, 0.22 mmol), Pd(PPh3)2Cl2 (15.4 mg, 0.022 mmol) and Cul (4.2 mg, 0.022 mmol) in triethyl amine (1 mL). The mixture was degassed with N2 for 10 minutes, 3- ethynyl-phenol (103 mg, 0.87 mmol) was added and the mixture degassed with N2 for 5 minutes. The reaction mixture was heated at 90 C for 5 hours. After cooling to ambient temperature, the crude mixture was filtered through celite and washed with dichloromethane. The filtrate was concentrated and purified by preparative thin layer chromatography eluting with ethyl acetate/hexane (30%) to give a solid intermediate. To the solid intermediate in tetrahydrofuran/methanol (1 mL/0.2 mL) was added sodium hydroxide solution (2 N in water, 0.2 mL, 0.4 mmol) and the solution was stirred at room temperature for 18 hours. 1 N hydrochloric acid aqueous solution was added dropwise until pH = 1 and the reaction mixture was purified through preparative HPLC to give 11 mg (14% for 2 steps) of the pure product as a white solid. LCMS (ESI) mlz 254.1 (M+l)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate; In tetrahydrofuran; water; at 20℃; for 0.0833333h; | Example 11 3-(1-[1-(2,5-Dimethylbenzyl)-1H-benzimidazol-2-yl]methyl}-1H-[1,2,3]triazol-4-yl)phenol 3-Ethynylphenol (0.07 mL, 0.7 mmol) and CuSO4.5H2O (0.02 g, 0.7 mmol) were added to a solution of Intermediate 3 (0.2 g, 0.7 mmol) in THF/water (1:1, 4 mL). A catalytic amount of sodium ascorbate was added and the mixture stirred at r.t. for 5 minutes. The reaction mixture was then poured into DCM/water. The organic layer was separated, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-40% EtOAc/DCM), yielding the title compound (0.06 g, 21%) as a pale brown solid. deltaH (d6-DMSO) 9.47 (s, 1H), 8.48 (s, 1H), 7.68 (d, J 3.5 Hz, 1H), 7.35 (d, J 5.5 Hz, 1H), 7.26-7.17 (m, 4H), 7.17 (d, J 7.9 Hz, 1H), 6.88 (d, J 7.3 Hz, 1H), 6.71 (d, J 7.2 Hz, 1H), 5.95 (s, 3H), 5.59 (s, 2H), 2.35 (s, 3H), 1.94 (s, 3H). LCMS (ES+) 410 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With palladium diacetate; trimethylphosphane; In acetone; at 60℃; for 5h;Inert atmosphere; | General procedure: A mixture of 0.05 mmol Pd(OAc)2 (11.2 mg, 10 mol %) and 0.15 mL of PMe3 solution (0.15 mmol, 1.0 M PMe3 dissolved in toluene, 30 mol %) was stirred at 110 C under argon for 10 min until all palladium acetate was dissolved. Then 0.5 mL of water or 1 mL acetone was added, followed by a mixture of terminal alkyne 1 (0.5 mmol) and acrolein (2) (2.5 mmol). The reaction mixture was then stirred at 60 C in an oil bath. After full conversion of the alkyne starting material, as shown by TLC, the reaction mixture was extracted with ethyl ether (3*10 mL), dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel (hexane:ethyl acetate=95:5 or 50:50) to give the pure product 35-(3-Hydroxyphenyl)pent-4-ynal (3e) Colorless liquid; 1H NMR (400 MHz, CDCl3) delta 9.83 (s, 1H), 7.13 (t, J=7.9 Hz, 1H), 6.94 (d, J=7.9 Hz, 1H), 6.88-6.84 (m, 1H), 6.81-6.76 (m, 1H), 5.67 (br, 1H), 2.81-2.67 (m, 4H); 13C NMR (100 MHz, CDCl3) delta201.5, 155.5, 129.7, 124.6, 124.3, 118.4, 115.6, 87.8, 81.3, 42.7, 12.8; HRMS (ESI) calcd for C11H9O2 (M+-H): 173.0603; Found: 173.0608. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.0% | With copper(l) iodide; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 28h; | To a stirred clear yellow solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.070 g, 0.140 mmol), <strong>[10401-11-3]3-ethynylphenol</strong> (0.083 g, 0.701 mmol) and DIEA (0.122 ml, 0.701 mmol) in THF (5 mL) was added CuI (0.053 g, 0.280 mmol) at rt. After 28 h, the reaction mixture was diluted with Et2O (50 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated to give yellow oil which was purified by prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0528 g, 0.085 mmol, 61.0% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) delta 7.75-7.99 (m, 2H), 7.52 (t, J=1.8 Hz, 1H), 7.22-7.30 (m, 2H), 6.84-6.89 (m, 1H), 6.51 (s, 1H), 5.97-6.07 (m, 1H), 5.86 (br. s., 1H), 5.78 (s, 2H), 5.44 (d, J=16.7 Hz, 1H), 5.19 (dd, J=1.6, 10.4 Hz, 1H), 4.14-4.29 (m, 2H), 4.00 (d, J=4.7 Hz, 2H), 2.62 (s, 3H), 1.82-2.03 (m, 3H), 1.65-1.73 (m, 1H), 1.31 (s, 3H), 1.24 (t, J=7.1 Hz, 3H), 1.23 (s, 9H). LCMS (M+H)=618.6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | at 800℃; under 0.000750075 Torr; | Compound 10a (161 mg, 0.79 mmol) was sublimed into the FVP apparatus at 170-180 C and pyrolyzed at 800 C and 103 hPa.The products were isolated in a liquid-N2 cold trap. After the end of the experiment, the CO2 and acetonitrile were removed under vacuum, and the remaining light-yellow, liquid product was distilled at 50 C and 1 hPa to yield 81 mg (87 %) of 10a as a colourless liquid. deltaH (DMSO-d6) 7.2-6.7 (m, 4H), 4.90 (br s, 1H,OH), 3.05 (s, 1H). numax (KBr)/cm-1 3600-3000 (br), 3280,2090, 1565-1610, 1465, 1430, 1135, 850, 770, 675. m/z (EI) 118(M, 100 %), 89 (18), 63 (10). HRMS m/z 118.0420; calcd forC8H6O 118.0419. The properties are in agreement with literature data. [10,12] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 1.5h;Inert atmosphere; | General procedure: Toa mixture of 2-iodo-3,4,6-tri-O-acetyl-D-glucal 1 (398 mg, 1 mmol) andDMF (5 mL) in a two neck round bottom flask under nitrogen was added palladiumacetate (11.2 mg, 5 mol%) and cesium carbonate (488.7 mg, 1.5 eq.). This wasthen followed by the dropwise addition of the terminal alkynes 2a-p (1.2 eq.) while stirring, at roomfor 0.3-5 hours. The color of the reaction mixture changes from a yellowish todark brown as the catalyst and base are added. After completion of reaction(TLC monitoring) concentrated aqueous solution of ammonium hydroxide (20 mL)was added to the reaction mixture and was extracted with ethyl acetate (3x25mL). The organic phase were combined and extracted with deionized/distilledwater (1x40 mL). The resulting organic phase was dried with magnesium sulfate,filtered and concentrated under vacuum. The product was purified by flashchromatography using ethyl acetate and hexane as eluents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In toluene; at 40℃; for 24h;Inert atmosphere; | Under nitrogen protection conditions,The intermediate 2-amino-5-bromo-3-benzyl-pyrazine (150 mg, 0.568 mmol)Phenylphosphine palladium dichloride (30 mg, 0.043 mmol), cuprous iodide (20 mg, 0.105 mmol), triphenylphosphine (10 mg, 0.038 mmol) were dissolved in 5 mL of toluene,Then join3-methyl-phenylacetylene (100 mg, 0.847 mmol) and triethylamine (0.4 mL). The reaction was stirred at 40 C for 24 hours. After the reaction was stopped, the reaction mixture was filtered and the filtrate was concentrated. Ethyl acetate and saturated sodium chloride solution were added. After the extraction, the ethyl acetate layer was dried over anhydrous sodium sulfate and filtered to give 62 mg of a yellow solid on a 200-300 mesh silica gel column. Yield 62% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With oxygen; potassium carbonate; In dimethyl sulfoxide; at 50℃; for 8h; | General procedure: In a 25ml two necked round bottom flask containing phenyl acetylene (1mmol), base (1mmol), catalyst (100mg) and DMSO (3ml), O2 gas was purged with the help of a balloon. The flask was heated at 50C for 8h and the progress of the reaction was monitored by TLC. After the completion of the reaction, the catalyst was separated while the solution was still hot and the reaction quenched by pouring the filtrate in chilled water. The reaction mixture was extracted with ethyl acetate and a light yellow crude product was isolated after removing the solvent in a rotary evaporator. The crude after purification was identified by NMR (Scheme 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20℃; for 1h;Inert atmosphere; | 3-(triisopropylsilyl)ethynyl)phenol (0.11 mmol, 31 mg) was dissolved in THF(1 ml) under nitrogen atmosphere and TBAF 1M in THF was added (0.12 mmol, 120 tl) for 1 h at room temperature. The reaction mixture was diluted with DCM, washed with brine, dried over sodium sulfate, filtered and evaporated to dryness.The crude was purified by flash column chromatography with eluentHexane/AcOEt 9:1 affording the title compound as yellow oil (13 mg, 95%). 1H NMR (400 MHz, CDC13) oe 7.25 - 6.73 (m, 4H), 4.75 (bs, 1H), 3.0 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In 1,4-dioxane; at 100℃; for 1.33333h;Inert atmosphere; Microwave irradiation; | A microwave vial under argon atmosphere was loaded with N-(6-bromo-1-trityl- 1 H-indazo 1-3 -yl)-4-(4-methylpiperazin- 1 -yl)-2-(2,2,2-trifluoro-N-(tetrahydropyran-4- yl)acetamido)benzamide (0.05 mmol, 44 mg), Cul (0.005 mmol, 1 mg), PdC12(PPh3)2(0.005 mmol, 4 mg) and PPh3 (0.01 mmol, 3 mg). The mixture was dissolved in a degassed mixture of dioxane/TEA (500 tl dioxane/ TEA 5 eq; 0.26 mmol, 36 tl). Finally 3- ethynylphenol was added (0.075 mmol, 9 tl). The reaction was carried out under irradiation at 100C for 80 minutes.The crude was directly purified by flash column chromatography with eluentDCM/MeOH 97:3 affording the title compound (15 mg, 33%).1H NMR (400 MHz, CDC13) oe 8.24 (s, 1H), 7.93 - 7.86 (m, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.32 - 7.18 (m, 15H), 7.18 - 7.10 (m, 2H), 6.99 (d, J 7.7 Hz, 1H), 6.87 (dd, J 6.5, 5.2 Hz, 2H), 6.77 (ddd, J 8.2, 2.6, 0.9 Hz, 1H), 6.63 (s, 1H), 6.51 (s, 1H), 4.64 (d, J = 11.8 Hz, 1H), 3.98 (d, J= 8.1 Hz, 1H), 3.83 (d, J 11.2 Hz, 1H), 3.50 (t, J 11.4 Hz, 1H), 3.42 (t, J= 11.6 Hz, 1H), 3.37 -3.22 (m, 4H), 2.68 -2.47 (m, 4H), 2.38 (s, 3H), 2.09 (d,J= 13.5 Hz, 1H), 1.79 (d,J 11.0 Hz, 1H), 1.68 (dd,J= 12.1, 4.4 Hz, 1H), 1.31 (dd,J = 12.4, 4.6 Hz, 1H).l3 NMR (101 MHz, CDC13) oe 164.0, 155.6, 153.2, 142.5, 142.4, 139.3, 136.9,135.9, 134.7, 134.6, 131.0, 130.9, 130.2, 129.7, 127.9, 127.6, 124.5, 124.4, 124.3, 123.4,122.5, 121.1 118.4, 118.1, 117.8, 117.1, 116.0, 114.2, 90.1, 89.2, 78.8, 67.4, 56.1, 54.6,47.4, 46.2, 31.4, 29.9, 29.6. (ESI+) MS: m/z 889.5 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.3% | With potassium carbonate; In N,N-dimethyl-formamide; for 6h;Reflux; | Dissolve <strong>[10401-11-3]3-ethynylphenol</strong> (710mg, 6.01mmol) in DMF (30mL), then add anhydrous potassium carbonate (1.65g, 12.02mmol) and benzyl chloride (1mL, 9.01mmol, 1.1g / mL) and heat to reflux Reaction 6h.The reaction was stopped, water (100 mL) was added to the reaction solution, dilute hydrochloric acid was added to adjust the pH to 1, and ethyl acetate was extracted three times (150 mL).The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE / EtOAc (v / v) = 90/1) to obtain 420 mg of pale yellow liquid, yield: 42.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With potassium carbonate; In dimethyl sulfoxide; at 20℃; | General procedure: A solution of potassium carbonate (0.122 g, 0.882 mmol) andcorresponding acetylenic alcohol (0.882 mmol) in 1 mL of anhydrousdimethyl sulfoxide was added to a mixture of 6,7-dichloro-5,8-quinolinedione 1 (0.1 g, 0.441 mmol). The reaction mixturewasstirred at room temperature for 3e24 h. Subsequently, the reactionmixture was evaporated under vacuum. The crude product waspurified by silica-gel flash column chromatography (chloroform/ethanol, 40:1, v/v) to give pure products 10e17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate; In tetrahydrofuran; at 20℃; | General procedure: To a mixture of 6,7-dichloro-5,8-quinolinedione 1 (0.1 g,0.441 mmol), a solution of potassium carbonate (0.061 g,0.441 mmol) and corresponding acetylenic alcohol (0.441 mmol) in1 mL of anhydrous tetrahydrofuran (THF) was added. The reactionmixture was stirred at room temperature for 3e24 h. The progressof reaction was monitored by thin layer chromatography (TLC).Subsequently, the reaction mixture was evaporated under vacuum.The crude product was purified by silica-gel flash column chromatography(chloroform/ethanol, 40:1, v/v) to give pure compounds2e9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With dmap; triethylamine; In chloroform; for 5h;Reflux; | General procedure: To a yellow solution of compound 7 or 66 (1 mmol) in newdistilled chloroform (80 mL), a solution of thionyl chloride (1.5 mL)in new distilled chloroform (10 mL) was added dropwise. Themixture solution was stirred and heated under reflux for 5 h andcooled to room temperature. The solvent was evaporated underreduced pressure. The yellow residuewas dissolved in new distilledchloroform (40 mL) and was added with a solution of DMAP(0.1 mmol), Et3N (1.2 mmol) and corresponding amines or alcohols(1.2 mmol) in new distilled chloroform (20 mL). The reactionmixture was stirred and heated under reflux for 5 h and cooled to room temperature. The solvent was evaporated under reducedpressure. The residue was purified by silica gel column chromatographyto give the amide or ester targets, respectively |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In acetone; at 70℃; for 7h; | In a 100 mL round bottom flask was added <strong>[10401-11-3]3-hydroxyphenylacetylene</strong> (3.31 g, 28.0 mmol), acetone (50 mL), 2-bromoacetamide (2.36 g, 17.1 mmol) and K2CO3 (5.53 g, 40.0 mmol),The reaction system was heated to 70 C for 7 h.The mixture was cooled to room temperature, filtered, and the solvent was evaporated to dryness and the crude product purified by column chromatography (petroleum ether/ethyl acetate (V/V) = 1/1) to give a white solid (2.70 g, 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With tetrabutylammomium bromide; sodium hydroxide; In chloroform; water; at 0 - 40℃; | In a recovery flask equipped with a dropping funnel, 4.96 g of the intermediate compound (L1) obtained above,0.69 g of tetrabutylammonium bromide (TBAB)Chloroform (50 mL) was added,And stirred at 0 C. to obtain a solution.To this solution,4.87 g of <strong>[10401-11-3]m-hydroxyphenylacetylene</strong>Of 1M aqueous sodium hydroxide solution41 mL was slowly added dropwise,After completion of dropping, 2 hours at 0 C.,And the mixture was stirred at 40 C. overnight.After completion of the reaction, the obtained reaction product liquid was transferred to a separatory funnel, washed three times with distilled water and three times with saline, and then transferred to an Erlenmeyer flask. Anhydrous sodium sulfate was then added to the Erlenmeyer flask, and the mixture was stirred overnight for dehydration.Thereafter, the liquid obtained finally was filtered to remove anhydrous sodium sulfate, and then chloroform was distilled off with an evaporator to obtain a crude product.This crude product was recrystallized from a mixed solvent of methanol and water and dried at 80 C. under reduced pressure to obtain a powdery white solid (yield 51%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I); tris(bipyridyl)ruthenium chloride dihydrate; In 1,4-dioxane; at 20℃;Irradiation; Inert atmosphere; Schlenk technique; | General procedure: Ru(bpy)3Cl2?2H2O (1.4 mg) and PPh3AuNTf2 (7.4 mg) was dissolved in dioxane (10 mL) and the mixture was degassed by bubbling with N2 for 15 min to get solvent A. Then, alkyne (0.2 mmol), thiosulfonylation reagent (0.4 mmol) and the solvent (1mL) was added to a Schlenk tube under N2 atmosphere. The reaction mixture was stirred under the irradiation by a blue LED strip (a fan was used to keep the reactionat room temperature) until complete consumption of the alkyne (2-6 h). The reaction mixture was evaporated under reduced pressure and purified by silica gel chromatography to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper(ll) sulfate pentahydrate; potassium iodide; In acetonitrile; at 20℃; for 0.166667h;pH 5.0; | General procedure: To acetonitrile (40 mL) was added the alkyne (2 mg). Bathophenanthrolinedisulfonic acid disodium salt hydrate (BPDS) (1 eq) was dissolved in purified water (100 muL) and added to the alkyne solution. The solution was vigorously stirred for 5 minutes. Finely ground potassium iodine (KI), (1eq) was added to the solution and vigorously mixed for a further 5 minutes. A solution of sodium acetate buffer (pH 5.0, 250 mM) was prepared. Copper (II) sulfate pentahydrate (1 eq, 5 muL) was mixed with the buffer and then added to the alkyne solution. Flash chromatography was then used to purify the compounds using a gradient mixture of petroleum ether and ethyl acetate. Solvents were then removed by rotary evaporator. Further purification was undertaken using reverse phase semi preparative HPLC as required. HPLC fractions were concentrated by rotary evaporator. Water and formic acid were removed by lyophilization, iodinated alkynes were then recovered. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sodium azide; copper; copper(II) sulfate; In water; N,N-dimethyl-formamide; for 1h;Microwave irradiation; | General procedure: To the solution of C-6 monotosylated L-ascorbic acid derivative 4 (200-350 mg) in DMF (8 ml), Cu (0.8 eq),1M CuSO4 solution (0.3 eq), NaN3 (2.5 eq) dissolved in H2O (2 ml)and the corresponding alkyne (1.2 eq) were added. The reaction mixture was heated for 1 h using microwave radiation (300 W). The solvent was evaporated and the product was purified with column chromatography on silica gel and aluminium oxide. The obtained oily compound was further triturated using n-hexane to obtain white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With copper; copper(II) sulfate; In water; N,N-dimethyl-formamide; tert-butyl alcohol; for 1h;Microwave irradiation; | General procedure: To the solution of 6-azido-2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid (6) (200-300 mg) in DMF (3 ml); tert-butanol(3 ml) and H2O (3 ml), Cu (0.8 eq), 1M CuSO4 solution (0.3 eq) and the corresponding alkyne (1.2 eq) were added. The reaction mixturewas heated for 1 h using microwave radiation (300 W). The solvent was evaporated and the product was purified by column chromatography on silica gel and aluminium oxide. The obtained oily compound was further triturated using n-hexane to obtainwhite powder |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With potassium hydroxide; In dichloromethane; water; at 20℃; for 2h; | To a solution of <strong>[10401-11-3]3-ethynylphenol</strong> (0.264 g, 2.235 mmol) in CH2CI2 (9 mL) was added aqueous potassium hydroxide (20 wt%) (3.13 mL, 13.41 mmol). (Bromodifluoromethyl)trimethylsilane (0.556 mL, 3 58 mmol) was then added via syringe and the reaction mixture was stirred at rt for 2 h. The mixture was transferred to a separatory funnel containing water (10 rnL). The aqueous layer was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were washed with brine (10 mL), dried over MgS04, filtered, and concentrated. The product was purified by column chromatography on silica gel (0% 20% ethyl acetate in hexanes; 40 g column) to afford l-(difluoromethoxy)-3-ethynylbenzene (195 mg, 1.160 mmol, 52% yield) as a colorless oil. NMR (400 MHz, CHLOROFORM-d) d 7.42 - 7.32 (m, 2H), 7 28 (br s, 1H), 7.15 (dt, .7=7 1, 2.1 Hz, 1H), 6.53 (t, J=73.5 Hz, 1H), 3.14 (s, 1H); 19F NMR (376 MHz, CHLOROFORM-d) d -80.98 (s, I F); 13C NMR (101 MHz, CHLOROFORM-d) d 150.5, 129.4, 128.8, 123.5, 122.7, 120.0, 115.3 (t, .7=260.5 Hz, 1C), 82.0, 77.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(ll) sulfate pentahydrate; sodium L-ascorbate; In water; N,N-dimethyl-formamide; at 20℃; for 14h;Inert atmosphere; | (+)-(C2R,3R,4S,5R,6S)~3-Acetoxy-6-(((3R,4R,5S)-5-azido~4-hydroxytetrahydro~ 2//-pyran-3 -yl)thio)-5-methoxy-4-(4-(3 ,4, 5-trifluorophenyl)- 1 H- 1,2,3 -triazol- 1 - yl)tetrahydro~2/:/~pyran~2-yl)methyl acetate (18 mg, 0 029 mmol) and <strong>[10401-11-3]3-ethynylphenol</strong> (10.35 mg, 0.088 mmol) were dissolved in a previously degassed solution of DMF (0.9 mL) and water (0.300 niL) and the mixture was placed under argon. Sodium ascorbate (6 94 mg, 0.035 mmol) and copper(II) sulfate pentahydrate (10 20 mg, 0.041 mmol) (predissolved in 0.3 mL water) were added and the reaction mixture was stirred at room temperature for 14 h. The mixture and the solid clinging to the stir bar were dissolved by the addition of dichloromethane and methanol. Water (5 mL) and saturated aqueous sodium bicarbonate (5 mL) were added resulting in the formation of a precipitate. The mixture was filtered through a pad of Ceiite and the filter cake was rinsed with 5% methanol in dichoromethane. The filtrate was transferred to a separatory funnel. Brine (10 ml.) w'as added and the aqueous layer was extracted (with gentle shaking) with 5% methanol in dichloromethane (4 x 20 mL). The combined organic layers were washed with brine (10 mL). The organic layer was dried over MgSOr, filtered, and concentrated. The product was purified by column chromatography on silica gel (20% ethyl acetate containing 5% ethanol/60% hexanes 80% ethyl acetate containing 5% methanol/20% hexanes; 12 g column) to afford ((2R,3R,4S,5R,6S)-3-acetoxy-6- i((3R,4R, 5 S)-4-hydroxy-5-(4-(3 -hy droxyphenyl)- //- 1 ,2,3 -tri azol- 1 ~yl)tetrahydro-2/:/- pyran-3 -y 1 )thio)-5-methoxy-4-(4-(3 ,4, 5-trifluorophenyl)- 1 H- 1 ,2,3 -tri azol- 1 - yl)tetrahydro~2/:/~pyran~2-yl)methyl acetate (15 mg, 0 020 mmol, 70% yield) as a white solid. 4 1 NMR (400 MHz, Acetone) d 8 81 (s, 1 }. 8 42 (s, 1 }. 7 74 (dd, 7=9.0, 6.8 Hz, 2H), 7.49 - 7.42 (m, 1H), 7.38 - 7.34 (m, 1H), 7.30 - 7.22 (m, 1H), 6.83 (ddd, 7=8.0, 2.5, 1.0 Hz, 1 H), 5.59 (d, 7=2.3 Hz, 1 1 1 ), 5.26 (dd, 7=40.5, 3.0 Hz, 1 1 1 ), 5.06 (d, 7=9.5 Hz, 1H), 4.75 - 4.61 (m, H i), 4.44 (t, 7=6.7 Hz, 1H), 4.32 - 4.12 (m, 7H), 3.98 (t, 7=11.2 Hz, 1 1 1 ).. 3.64 (t, 7=11.7 Hz, 1 1 1 ), 3.36 (s, 3H), 2.10 (s, 3H), 1.99 (s, 31 1 ). LC/MS (ESI) m/e 735.3 [(M+H)+, calcd for C32H34F3N6O9S 735.2], fe = 2.03 min (Method 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With N-iodo-succinimide; acetic acid; lithium chloride; In dichloromethane; at -10℃; for 18h; | General procedure: A 10 mL glass vial with a screw cap was charged with alkynes (0.2 mmol), NIS (0.3 mmol, 1.5equiv.), LiCl (0.4 mmol, 2 equiv.) and a solvent mixture of DCM (0.5 mL) and HOAc (0.5 mL).The reaction mixture was stirred at -10 oC for 18 h. Upon completion, the reaction mixture was quenched with saturated NaCl solution and was extracted with EtOAc, the combined organic layers were dried with anhydrous Na2SO4 and the solvent was removed in vacuum. The residue was purified by flash silica gel column chromatography (eluted with hexanes and ethyl acetate) togive the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With nitromethane; trifluoromethylsulfonic anhydride; acetic acid In formic acid at 80 - 120℃; | 94 Example 94 m-Hydroxyacetanilide Take a reaction tube, add 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of m-hydroxyphenylacetylene, 0.5mL of acetic acid,Trifluoromethanesulfonic anhydride 150-200mg (0.6mmol), formic acid 30-60mg (0.75mmol), stirred at 80-120°C for 1-72 hours. After the completion of the reaction, 10 mL of sodium hydroxide solution was added to quench the reaction, extracted with ethyl acetate 3 times, the organic phase was washed with 5 mL of brine, and the organic phases were combined and separated by column chromatography to obtain 9.1 mg of m-hydroxyacetanilide with a yield of 20%. |
20% | With formic acid; nitromethane; trifluoromethylsulfonic anhydride In acetic acid at 100℃; for 12h; |
Tags: 10401-11-3 synthesis path| 10401-11-3 SDS| 10401-11-3 COA| 10401-11-3 purity| 10401-11-3 application| 10401-11-3 NMR| 10401-11-3 COA| 10401-11-3 structure
[ 89414-50-6 ]
(2-Ethynyl-5-methoxyphenyl)methanol
Similarity: 0.76
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