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CAS No. : | 62875-84-7 | MDL No. : | MFCD00031420 |
Formula : | C9H10INO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ICFCBYVKPRHTPR-UHFFFAOYSA-N |
M.W : | 291.09 | Pubchem ID : | 459320 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium hydroxide for 1h; Heating; | |
95% | With potassium hydroxide In methanol at 50℃; for 12h; | |
93% | With potassium hydroxide In methanol at 50℃; |
93% | With potassium hydroxide In methanol; water at 50℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethane for 48h; | |
95% | With hydrogenchloride; potassium periodate; potassium iodide In methanol at 20℃; for 6h; | |
95% | With sodium (meta)periodate; glacial acetic acid; potassium iodide; sodium chloride In water monomer for 0.166667h; Inert atmosphere; |
94% | With iodine; silver sulphate In ethanol for 0.5h; | |
94% | With iodine; silver sulphate In ethanol at 20℃; for 0.5h; | |
94% | With iodine; silver sulphate In ethanol at 20℃; | |
92% | With iodine; silver sulphate In ethanol at 20℃; for 1h; | |
90% | With iodine; Sodium hydrogenocarbonate In dichloromethane for 20h; Ambient temperature; | |
87% | With potassium metaperiodate; glacial acetic acid; potassium iodide; sodium chloride In water monomer at 20℃; for 24h; | |
86% | With iodine; silver sulphate In ethanol at 20℃; for 0.5h; | |
86% | With iodine; silver sulphate In ethylene glycol | |
86% | With dihydrogen peroxide; iodine In water monomer; 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran; chlorobenzene | 10 Ethyl 4-amino-3-iodobenzoate: Ethyl 4-amino-3-iodobenzoate: Ethyl 4-aminobenzoate (15.00 g, 91 mmol) and iodine (11.80 g, 46.5 mmol) were mixed with water (80 mL) and chlorobenzene (4.60 g, 41 mmol). The mixture was stirred while the temperature was gradually raised to 90° C. over 30 min. Hydrogen peroxide (30%, 50 mL) was added over 10 h at 90° C. After stirring at that temperature for an additional 6 h, the mixture was cooled and the solution decanted from the residual solids. The solids were dissolved in DCM and the solution washed successively with sodium thiosulfate and brine. After drying (MgSO4), the solvent was removed under reduced pressure and the resulting brown solid was triturated with hexane to remove di-iodinated by-products. The desired compound was obtained as a brown solid (22.85 g, 86% yield). |
86% | With iodine; silver sulphate In ethanol at 20℃; for 0.5h; | |
85% | With sodium (meta)periodate; potassium iodide; sodium chloride In glacial acetic acid | 4; 2 An exemplary procedure for preparing a comb polymer is provided hereinbelow. The preparation of one component of the monomeric building unit, Compound 106, on the route for the preparation of an exemplary comb polymer, was carried out as illustrated in Scheme 2 below |
85% | ||
85% | With iodine; silver sulphate In ethanol at 20℃; for 0.5h; | |
85% | With Iodine monochloride; calcium carbonate In ethanol; water monomer at 18℃; for 15h; | |
84% | With iodine; silver sulphate In ethanol | |
81% | With iodine; Sodium hydrogenocarbonate In dichloromethane; water monomer at 20℃; for 20h; Darkness; | |
79% | With N-iodo-succinimide; sulfuric acid In acetonitrile at 20℃; for 2h; | |
70% | With sodium (meta)periodate; glacial acetic acid; potassium iodide; sodium chloride In water monomer at 20℃; | |
With N,N,N-trimethylbenzenemethanaminium dichloroiodate; calcium carbonate In methanol; dichloromethane at 25℃; | ||
20.7 g (90%) | With N-iodo-succinimide In N,N-dimethyl-formamide | 7 Preparation 7 Preparation 7 Ethyl 4-amino-3-iodobenzoate To a solution of ethyl 4-aminobenzoate (13.0 g) in DMF (33 mL) is added a solution of N-iodosuccinimide (18.6 g) in DMF (39 mL). The reaction is stirred at room temperature overnight. The mixture is poured into 800 mL water. The resulting solid is collected and dried to yield 20.7 g (90%) of the titled compound. Physical characteristics are as follows: m.p. 71-74° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.10, 7.65, 6.74, 4.21, 1.27; IR (drift) 3455, 3364, 1688, 1615, 1592, 1364, 1324, 1292, 1286, 1249, 1152, 1127, 818, 762, 671 cm-1; OAMS supporting ions at: ESI+291.9 ESI-289.9; Anal. calcd for C9H10INO2: C, 37.14; H, 3.46; N, 4.81, found: C, 37.02; H, 3.44; N, 4.81. |
20.7 g (90%) | With N-iodo-succinimide In N,N-dimethyl-formamide | 6 Preparation 6 Preparation 6 Ethyl 4-amino-3-iodobenzoate To a solution of ethyl 4-aminobenzoate (13.0 g) in DMF (33 mL) is added a solution of N-iodosuccinimide (18.6 g) in DMF (39 mL). The reaction is stirred at room temperature overnight. The mixture is poured into 800 mL water. The resulting solid is collected and dried to yield 20.7 g (90%) of the titled compound, m.p. 71-74° C. 1H NMR (300 MHz, DMSO-d6) δ8.10, 7.65, 6.74, 4.21, 1.27; IR (drift) 3455, 3364, 1688, 1615, 1592, 1364, 1324, 1292, 1286, 1249, 1152, 1127, 818, 762, 671 cm-1; OAMS supporting ions at: ESI+291.9, ESI-289.9; Anal. calcd for C9H10INO2: C, 37.14; H, 3.46; N, 4.81, found: C, 37.02; H, 3.44; N, 4.81. |
With Sodium hydrogenocarbonate In dichloromethane; water monomer; ethyl acetate | 30.A N-[2-Iodo-4-Dimethylhydroxymethylphenyl]-N-Ethyl-4-6-Dichloro-1,3,5 Triazin-2-Amine Part A: Ethyl 4-aminobenzoate (5.0 gr, 30.27 mmol) and sodium bicarbonate (3.81 g, 45.40 mmol, 1.5 eq.) were added to a 50:50 mixture of methylene chloride and water. The mixture was chilled to 0 degree and I2 (11.53 g, 45.40 mmol, 1.5 eq.) was added slowly. The reaction mixture was allowed to come to room temperature and was stirred for 72 hours. The layers were then separated and the aqueous layer washed with methylene chloride. All organics were combined and dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was chromatographed on silica using 30% ethyl acetate in hexanes as solvent to afford ethyl 3-iodo-4-aminobenzoate. C9 H10 NO2 I MS 292 (M+H)+ 309 (M+NH4)+. | |
With iodine In ethanol | ||
1.5 g | With silver(II) sulfate; iodine In ethanol at 22 - 26℃; for 1h; | 1 Step-i:- Preparation of ethyl 4-amino-3-iodobenzoate To a solution of iodine (3.01 g, 11.8 mmol) in EtOH (50 mL) was added silver sulphate (3.75 g, 11.8 mmol) and ethyl 4-aminobenzoate (step-i, Intermediate-33, 1.0 g).The reactionmixture was stirred at RT for 1 h. The reaction mass was filtered and excess of EtOH was removed under vacuum. The reaction mass was diluted with DCM and washed with aq. sodium thiosulphate and again concentrated to afford 1.5 g of title compound. ‘H NMR (300MHz, DMSO-d6): 8.10 (s, 1H),7.66-7.63 (d, J= 8.4 Hz, 1H), 6.75-6.72 (d, J= 8.7 Hz, 1H), 6.05 (s, 2H), 4.23-4.16 (q, J= 7.2Hz, 2H), 1.28-1.24 (t, J= 7.Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In dichloromethane Heating; | |
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper; potassium carbonate In N,N-dimethyl-formamide for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With sulfuric acid In toluene for 2h; Heating; | |
87% | With sulfuric acid In toluene Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium carbonate In N,N-dimethyl-formamide at 100℃; for 6h; | |
74% | With sodium carbonate In N,N-dimethyl-formamide at 100℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine In toluene at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine In toluene at 20℃; for 2h; | |
92% | With piperidine; tetrabutylammomium bromide; triphenylphosphine In tetrahydrofuran; water at 20℃; | |
89% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | General procedure for the preparation of the alkynylanilines 2 General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 μl, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 μl, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-(3,5-dimethylphenyl)acetylene; 3-iodobenzocaine With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 10℃; Stage #2: In acetonitrile Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 3-iodobenzocaine With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Stage #2: pyrrolidine With potassium carbonate In water; acetonitrile at 0℃; for 0.5h; | |
78% | Stage #1: 3-iodobenzocaine With hydrogenchloride; sodium nitrite In acetonitrile at 0℃; for 0.5h; Stage #2: pyrrolidine With potassium carbonate In water; acetonitrile at 20℃; | |
Stage #1: 3-iodobenzocaine With hydrogenchloride In water; acetonitrile at -10 - 20℃; for 0.25h; Stage #2: With sodium nitrite In water; acetonitrile for 0.5h; Stage #3: pyrrolidine With potassium carbonate In water; acetonitrile at -10 - 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2 g | Stage #1: 3-iodobenzocaine With tert.-butylnitrite; boron trifluoride diethyl etherate In tetrahydrofuran at -20℃; Stage #2: piperazinyl-N-methylpolystyrene With pyridine In tetrahydrofuran; acetonitrile at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With toluene-4-sulfonic acid In toluene for 4h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With pyridine In 1,4-dioxane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; diethylamine at 25℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Schlenk technique; | ||
With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In tetrahydrofuran at 20℃; |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: 3-iodobenzocaine With hydrogenchloride; sodium nitrite for 0.5h; Stage #2: With potassium iodide In water at 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: CuI; diethylamine / PdCl2(PPh3)2 / 25 °C 2: potassium carbonate / methanol / 25 °C | ||
Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere; Schlenk technique 2: potassium carbonate / methanol / 2 h / 20 °C / Inert atmosphere; Schlenk technique | ||
Multi-step reaction with 2 steps 1: triethylamine; trans-bis(triphenylphosphine)palladium dichloride; copper(l) iodide / tetrahydrofuran / 20 °C 2: potassium carbonate; methanol / water / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 71 percent / pyridine / dioxane / 12 h / 20 °C 2.1: CuCN*2LiCl / tetrahydrofuran; 1,2-dimethoxy-ethane / 0.33 h 2.2: 75 percent / Fe(acac)3 / tetrahydrofuran; 1,2-dimethoxy-ethane / 4 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 40 percent / TsOH*H2O / toluene / 4 h / Heating 2: 81 percent / Cs2CO3; tri(p-tolyl)phosphine; Pd(OAc)2 / toluene / 12 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C | ||
Multi-step reaction with 2 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C | ||
Multi-step reaction with 3 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation | ||
Multi-step reaction with 5 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 5 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C | ||
Multi-step reaction with 4 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 75 percent / I2; MeI / 336000 h / 110 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 75 percent / I2; MeI / 336000 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 9 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C | ||
Multi-step reaction with 8 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 10.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 11.1: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 9 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C |
Multi-step reaction with 11 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 10.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 11.1: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 10.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C | ||
Multi-step reaction with 8 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C |
Multi-step reaction with 10 steps 1.1: 93 percent / KOH / methanol; H2O / 12 h / 50 °C 2.1: HCl; NaNO2 / H2O; acetonitrile / 0.5 h / -5 °C 2.2: 76 percent / K2CO3 / H2O; acetonitrile / 90 h / -5 - 20 °C 3.1: 91 percent / 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 12 h / 0 - 20 °C 4.1: 99 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / 12 h / 20 °C 5.1: 81 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 6.1: 81 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 7.1: 83 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 8.1: 87 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C 9.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran; H2O / 0.08 h / 0 °C 10.1: 77 percent / CuI; triethylamine / Pd(PPh3)2Cl2 / tetrahydrofuran / 12 h / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 75 percent / MeI; I2 / 336000 h / 110 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 75 percent / MeI; I2 / 336000 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 9.1: 94 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 94 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C | ||
Multi-step reaction with 9 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 9.1: 94 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C | ||
Multi-step reaction with 8 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 68 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 9.1: 77 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C | ||
Multi-step reaction with 7 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 77 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C | ||
Multi-step reaction with 6 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 86 percent / I2; MeI / 1 h / 150 °C / microwave irradiation 6.1: 77 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C |
Multi-step reaction with 9 steps 1.1: 93 percent / aq. KOH / methanol / 50 °C 2.1: aq. HCl; NaNO2 / acetonitrile / -5 °C 2.2: 76 percent / aq. K2CO3 / acetonitrile / -5 - 20 °C 3.1: dimethylaminopyridine; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide / CH2Cl2 / 0.33 h / 0 °C 3.2: 91 percent / CH2Cl2 / 0 - 20 °C 4.1: 99 percent / Pd(PPh3)2Cl2; CuI; Et3N / 20 °C 5.1: 81 percent / aq. TBAF / tetrahydrofuran; hexane / 0.08 h / 0 °C 6.1: 81 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 7.1: 83 percent / aq. TBAF / tetrahydrofuran; hexane / 0.25 h / 0 °C 8.1: 87 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C 9.1: 77 percent / Pd(PPh3)2Cl2; CuI; Et3N / tetrahydrofuran / 55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 78 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C 3.1: 72 percent / Ne3SiI / CH2Cl2 / 0.33 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 86 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C 3.1: 78 percent / Ne3SiI / CH2Cl2 / 0.33 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 80 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C 3.1: 76 percent / CH3I / 24 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 86 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 78 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 4 h / -40 - -15 °C 2.2: ZnBr2 / tetrahydrofuran / 1 h / -20 - -5 °C 2.3: 80 percent / Pd(PPh3)4 / tetrahydrofuran / 3 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: HCl; NaNO2 / H2O / 0.5 h / 0 °C 1.2: 88 percent / K2CO3 / H2O; acetonitrile / 0.5 h / 0 °C 2.1: iPrMgCl*LiCl / tetrahydrofuran / 0.67 h / -40 °C 2.2: 80 percent / CuCN*2LiCl / tetrahydrofuran / -30 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: pyridine 2: Et3N; CuI / (Ph3P)2PdCl2 / tetrahydrofuran; dimethylformamide 3: 100 percent / MnO2 / CH2Cl2 / 8 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine 2: Et3N; CuI / (Ph3P)2PdCl2 / tetrahydrofuran; dimethylformamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: pyridine 2: Et3N; CuI / (Ph3P)2PdCl2 / tetrahydrofuran; dimethylformamide 3: 100 percent / MnO2 / CH2Cl2 / 8 h / 20 °C 4: 82 percent / toluene; CHCl3 / 48 h / 20 °C 5: 87 percent / NaOAc; hydroquinone / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: pyridine 2: Et3N; CuI / (Ph3P)2PdCl2 / tetrahydrofuran; dimethylformamide 3: 100 percent / MnO2 / CH2Cl2 / 8 h / 20 °C 4: 82 percent / toluene; CHCl3 / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NaH In ethyl acetate; N,N-dimethyl-formamide | 30.B N-[2-Iodo-4-Dimethylhydroxymethylphenyl]-N-Ethyl-4-6-Dichloro-1,3,5 Triazin-2-Amine Part B: The product from part A (1.0 g, 3.4 mmol) was added to a stirring solution of NaH (0.21 gr, 5.2 mmol) in 25 mL of dry DMF and allowed to stir at room temperature for 10 minutes. Ethyl iodide (0.8 g, 5.2 mmol) was then added and the mixture as allow to stir for 24 hours. The reaction was then poured into water and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude material was chromatographed on silica using 30% ethyl acetate in hexanes as solvent to afford ethyl 3-iodo-4-(N-ethyl)aminobenzoate. C11 H14 NO2 I MS 320(M+H)+. | |
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide | 11 Ethyl 2-phenyl-3-methyl-indole-5-carboxylate: Ethyl 2-phenyl-3-methyl-indole-5-carboxylate: Adapting the procedure of H. -C. Zhang (Tet. Lett. 1997, 38, 2439) ethyl 4-amino-3-iodobenzoate (from example 10, 0.500 g, 1.72 mmol) was dissolved in DMF (5 mL) and LiCl (0.073 g, 1.72 mmol, 1 equivalent), PPh3 (0.090 g, 0.34 mmol, 0.2 equivalent), K2CO3 (1.188 g, 8.6 mmol, 5 equivalents) and phenylpropyne (0.645 mL, 5.76 mmol, 3 equivalents) were added. The solution was degassed by purging with argon for 1 h and palladium acetate (0.039 g, 0.17 mmol, 0.1 equivalent) was added. The mixture was stirred at 80° C. under argon for 20 h. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (50 mL). The extract was washed with brine (3*25 mL) and dried (MgSO4). Concentration under reduced pressure and purification by flash chromatography with 10-15% EtOAc-hexane gave the desired 2-phenyl-3-methyl indole (0.275 g, least polar component) and the 3-phenyl-2-methyl isomer (0.109 g, more polar component). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With calcium carbonate In methanol; diethyl ether; dichloromethane | 93.A ethyl 4-amino-3-iodobenzoate EXAMPLE 93A ethyl 4-amino-3-iodobenzoate A solution of ethyl 4-aminobenzoate (6.0 g, 36 mmol) in dichloromethane (1 10 mL) and methanol (65 mL) at room temperature was treated with calcium carbonate (10.8 g, 108 mmol) and benzyltrimethylammonium dichloroiodate (25 g, 72 mmol), stirred for 16 hours, and filtered. The filtrate was washed with 5% NaHSO3, dried (Na2SO4), filtered, and concentrated to provide a solid. The solid was recrystallized from ethanol and water, treated with diethyl ether, stirred for 30 minutes, and filtered. The filtrate was concentrated to provide the desired product. MS (DCI/NH3) m/z 292 (M+H)+and 309 (M+NH4)+; 1H NMR (300 MHz, CDCl3) δ 8.33 (d, 1H), 7.82 (dd, 1H), 6.70 (d, 1H), 4.51 (br s, 2H), 4.42 (q, 2H), 1.38 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With diisobutylaluminium hydride In tetrahydrofuran | 4; 2 An exemplary procedure for preparing a comb polymer is provided hereinbelow. The preparation of one component of the monomeric building unit, Compound 106, on the route for the preparation of an exemplary comb polymer, was carried out as illustrated in Scheme 2 below |
80% | With diisobutylaluminium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; | |
With hydrogenchloride; diisobutylaluminium hydride In dichloromethane | 8 Preparation 8 Preparation 8 (4-amino-3-iodophenyl)methanol To a solution of ethyl 4-amino-3-iodobenzoate (8.0 g) in CH2Cl2 (56 mL) cooled to 0° C. is added diisobutylaluminum hydride in CH2Cl2 (110 mL of a 1M solution). The reaction is stirred at 0° C. for 2 h then quenched by the addition of MeOH (50 mL). To this is added 1N HCl (100 mL). The mixture is concentrated to remove the organics. The aqueous solution is extracted with CH2Cl2 (3*). The combined organic layers are dried over Na2SO4, filtered and condensed. The resulting residue is adsorbed onto silica and chromatographed (Biotage flash 40M, eluent CH2Cl2 (2L), 1% MeOH/CH2Cl2 (2L), 2% MeOH/CH2Cl2). Fractions homogeneous by TLC are combined and condensed to afford (4-amino-3-iodophenyl)methanol. Physical characteristics are as follows: 1H NMR (300 MHz, DMSO-d6) δ 7.49, 7.01, 6.70, 6.00, 4.95, 4.28. |
With diborane In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; triphenylphosphine In N,N-dimethyl-formamide | 12 Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate A mixture of ethyl 4-amino-3-iodobenzoate {Hirschfeld et al. J. Med Chem. 1992, 35, 2231-2238.} (7.80 g, 26.8 mmol), [5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-pentynyl]tri methylsilane (9.41 g, 34.8 mmol), tetra-n-butylammonium chloride (7.44 g, 26.8 mmol), sodium carbonate (14.20 g,.134 mol), triphenylphosphine (0.35 g, 1.3 mmol), and palladium (II) acetate (0.30 g, 1.3 mmol) in 200 mL of DMF, was heated at 98° C. under N2 for 2 h. The solution was cooled, and the bulk of the DMF was removed in vacuo. The mixture was diluted with ethyl acetate, and the organic solution was washed with aqueous NaHCO3, dried (brine, MgSO4), filtered, and concentrated in vacuo. Silica gel chromatography (10:1 hexanes-EtOAc) of the concentrate yielded the title compound (7.49 g, 65%) as a crystalline solid. Recrystallization from hexanes provided an analytical sample as a white crystalline solid: mp 115°-116° C. Anal. Calcd for C23 H39 N1 O3 Si2: C 63.69; H, 9.06; N, 3.23. Found: C, 63.54; H, 9.11; N, 3.17. | |
With sodium carbonate; triphenylphosphine In N,N-dimethyl-formamide | 12 Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate A mixture of ethyl 4-amino-3-iodobenzoate {Hirschfeld et al. J. Med Chem. 1992, 35, 2231-2238.} (7.80 g, 26.8 mmol), [5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-pentynyl]trimethylsilane (9.41 g, 34.8 mmol), tetra-n-butylammonium chloride (7.44 g, 26.8 mmol), sodium carbonate (14.20 g, 0.134 mol), triphenylphosphine (0.35 g, 1.3 mmol), and palladium (II) acetate (0.30 g, 1.3 mmol) in 200 mL of DMF, was heated at 98° C. under N2 for 2 h. The solution was cooled, and the bulk of the DMF was removed in vacuo. The mixture was diluted with ethyl acetate, and the organic solution was washed with aqueous NaHCO3, dried (brine, MgSO4), filtered, and concentrated in vacuo. Silica gel chromatography (10:1 hexanes-EtOAc) of the concentrate yielded the title compound (7.49 g, 65%) as a crystalline solid. Recrystallization from hexanes provided an analytical sample as a white crystalline solid: mp 115°-116° C. Anal. Calcd for C23H39N1O3Si2: C, 63.69; H, 9.06; N, 3.23. Found: C, 63.54; H, 9.11; N, 3.17. | |
With sodium carbonate; triphenylphosphine In N,N-dimethyl-formamide | 12 Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate Ethyl 3-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]prop-1-yl]-2-trimethylsilyl-1H-indole-5-carboxylate A mixture of ethyl 4-amino-3-iodobenzoate {Hirschfeld et al. J. Med Chem. 1992, 35, 2231-2238.}(7.80 g, 26.8 mmol), [5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-pentynyl]trimethylsilane (9.41 g, 34.8 mmol), tetra-n-butylammonium chloride (7.44 g, 26.8 mmol), sodium carbonate (14.20 g, 0.134 mol), triphenylphosphine (0.35 g, 1.3 mmol), and palladium (II) acetate (0.30 g, 1.3 mmol) in 200 mL of DMF, was heated at 98° C. under N2 for 2 h. The solution was cooled, and the bulk of the DMF was removed in vacuo. The mixture was diluted with ethyl acetate, and the organic solution was washed with aqueous NaHCO3, dried (brine, MgSO4), filtered, and concentrated in vacuo. Silica gel chromatography (10:1 hexanes-EtOAc) of the concentrate yielded the title compound (7.49 g, 65%) as a crystalline solid. Recrystallization from hexanes provided an analytical sample as a white crystalline solid: mp 115- 116° C. Anal. Calcd for C23 H39 N1 O3 Si2: C 63.69; H, 9.06; N, 3.23. Found: C, 63.54; H, 9.11; N, 3.17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridine In benzene for 32h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In dimethyl sulfoxide at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With 1,4-diaza-bicyclo[2.2.2]octane; palladium diacetate In N,N-dimethyl-formamide at 105℃; for 16h; Inert atmosphere; | 4.2.2.1. 5-(Ethoxycarbonyl)-3-methyl-1H-indole-2-carboxylic acid (3a) To a solution of iodo compound 2 (1.00 g, 3.44 mmol) in anhydrous DMF (10 mL) under argon, 2-oxobutyric acid (1.75 g, 17.18 mmol) and DABCO (1.16 g, 10.31 mmol) were added. The solution was stirred for 5 min before addition of palladium(II) diacetate (0.04 g, 0.17 mmol). The mixture was warmed to 105 °C for 16 h. After cooling to room temperature, DMF was removed by evaporation and the resulting solid was dissolved in EtOAc (150 mL) and extracted with NaOH (1 M, 4 × 150 mL). The aqueous layers were combined, neutralized with HCl (1 M) and extracted with EtOAc (3 × 150 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo to obtain a brown solid which was purified by trituration in diethyl ether to give the desired indole 3a as pale brown powder (0.55 g, 2.24 mmol, 65%); mp: 265-266 °C; Rf = 0.32 (SiO2, Cyc/EtOAc, 7:3); 1H NMR (400 MHz, CD3OD) δ 8.39 (d, J = 2.0, 1H, H-4), 7.90 (dd, J = 9.0, 2.0, 1H, H-6), 7.43 (d, J = 9.0, 1H, H-7), 4.38 (q, J = 7.0, 2H, CH2), 2.63 (s, 3H, CH3), 1.42 (t, J = 7.0, 3H, CH3); 13C NMR (101 MHz, CD3OD) δ 169.2 (CO), 165.1 (CO), 140.3 (C), 129.2 (C), 126.9 (C), 126.6 (CH), 124.5 (CH), 122.7 (C), 121.8 (C), 112.8 (CH), 61.9 (CH2), 14.7 (CH3), 9.9 (CH3); HR-ESIMS: (M+H)+ m/z calcd for C13H14NO4 248.0923, found 248.0926. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: di-<i>tert</i>-butyl dicarbonate; 3-iodobenzocaine With dmap; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: With sodium hydroxide In ethanol at 20℃; for 12h; Stage #3: In water Acidic aq. solution; | 4.2.3.1. Benzyl 4-(bis(tert-butoxycarbonyl)amino)-3-iodobenzoate (10) To a solution of 2 (4.00 g, 13.65 mmol) in DCM (100 mL) DMAP (0.166 g, 1.36 mmol), triethylamine (1.9 mL, 13.65 mmol) and (Boc)2O (6.260 g, 28.66 mmol) were added. The mixture was stirred at room temperature for 1 h and washed with HCl (0.1 M). The organic layer was concentrated and the resulting solid was directly engaged into the next step with EtOH (200 mL) and NaOH (1 M, 40 mL). The solution was stirred for 12 h at room temperature and then concentrated to remove ethanol. The resulting solid was dissolved in water, acidified to pH 3 and then extracted with EtOAC. The organic layer was concentrated to give the intermediate product 9 which was directly engaged into next step. To a solution of this intermediate in DMF (100 mL), CDI (2.43 g, 15.01 mmol) and benzylic alcohol (1.56 mL, 15.0 mmol) were added. The mixture was stirred for 24 h, then concentrated and purified by FC (100% Cyc to 100% EtOAc) to give the desired product 10 as pale yellow foam (7.17 g, 12.97 mmol, 95%); Rf = 0.60 (SiO2, Cyc/EtOAc, 9:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H, H-2), 8.06 (d, J = 8.0, 1H, H-6), 7.47-7.25 (m, 6H, H-5, 5 × CHar), 5.37 (s, 2H, CH2), 1.42-1.39 (m, 18H, 6 × CH3); 13C NMR (101 MHz, CDCl3) δ 164.6 (CO), 149.8 (2 × CO), 146.4 (C), 140.4 (CH), 135.7 (C), 130.7 (C), 130.4 (2 × CH), 128.9 (CH), 128.8 (CH), 128.7 (CH), 128.6 (2 × CH), 99.7 (C), 83.51 (2 × C), 67.4 (CH2), 28.0-27.0 (6 × CH3); HR-ESIMS: (M+Na)+ m/z calcd for 576.0859, found 576.0879.4.2.3.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With palladium diacetate; sodium carbonate; triphenylphosphine In 1,2-dimethoxyethane; water at 80℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With 1,10-Phenanthroline; copper(II) choride dihydrate; potassium carbonate; sulfur In water at 100℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In ethyl acetate at 0℃; for 6.5h; Reflux; | ||
With triethylamine In dichloromethane at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium carbonate In N,N-dimethyl-formamide at 40℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With copper(I) oxide; caesium carbonate; N,N`-dimethylethylenediamine In N,N-dimethyl-formamide at 140℃; for 16h; Inert atmosphere; | General experimental procedure General procedure: A flask was charged with Cu2O (14 mg, 0.1 mmol), Cs2CO3 (977 mg, 3 mmol), o-haloaniline (1 mmol) and amidine hydrochloride (1.5 mmol) in 2 mL DMF under nitrogen atmosphere. The mixture was stirred at room temperature and DMEDA (20 mL, 0.2 mmol) was added via syringe. The reaction mixture was then stirred in a preheated oil bath at 140 C for 16 h, and then cooled to room temperature. The inorganic salt was filtered off and ethyl acetate, water was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated in vacuum.The residue was purified by column chromatography on silica gelusing petroleum ether/ethyl acetate as eluent to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: 3-iodobenzocaine With hydrogenchloride In acetonitrile at 20℃; for 0.25h; Stage #2: With sodium nitrite In acetonitrile for 0.5h; Stage #3: pyrrolidine With potassium carbonate In acetonitrile | |
Stage #1: 3-iodobenzocaine With hydrogenchloride In water; acetonitrile at -10 - 20℃; for 0.25h; Stage #2: With sodium nitrite In water; acetonitrile for 0.5h; Stage #3: pyrrolidine With potassium carbonate In water; acetonitrile at -10 - 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Stage #1: 1,4-bis(trimethylsilyl)-1,3-butadiyne With methyllithium lithium bromide In tetrahydrofuran; diethyl ether at 0 - 18℃; for 1.5h; Inert atmosphere; Stage #2: 3-iodobenzocaine With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine hydrochloride; triethylamine In tetrahydrofuran; diethyl ether at 18℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 3-iodobenzocaine With hydrogenchloride; sodium nitrite In water; acetonitrile at 0℃; Stage #2: diethylamine With potassium carbonate In water; acetonitrile at 0 - 20℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium phosphate; oxygen; palladium diacetate; potassium iodide; calcium chloride; copper dichloride; Trimethylacetic acid In acetonitrile at 100℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: 3-iodobenzocaine With hydrogenchloride In water; acetonitrile at -10 - 0℃; for 0.25h; Inert atmosphere; Stage #2: With sodium nitrite In water; acetonitrile at -10℃; for 0.5h; Inert atmosphere; Stage #3: N-methylaniline With potassium carbonate In water; acetonitrile at 0 - 20℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium cyanoborohydride; acetic acid In water; acetonitrile for 72h; | |
67% | With sodium cyanoborohydride; acetic acid In acetonitrile at 20 - 90℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 38% 2: 31% | With sodium cyanoborohydride; acetic acid In water; acetonitrile at 19 - 27℃; for 168h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | General procedure for the preparation of the alkynylanilines 2 General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 μl, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 μl, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With copper(l) iodide; caesium carbonate; 1,1'-bi-2-naphthol In dimethyl sulfoxide at 50℃; for 7h; Inert atmosphere; | 4.3. General procedure for synthesis of 3 and 4 General procedure: A mixture of ethyl 4-amino 3 iodo benzoate 2 (3.9 g,13.39 mmol), ethylacetoacetate or tert-butyl acetoacetate (18.75 mmol), CuI (254 mg, 1.339 mmol), BINOL (766 mg,2.67 mmol) and Cs2CO3 (4.362 g, 13.39 mmol) in dry DMSO(30 mL) was stirred at 50 C for 7 h under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and washed with a saturated solution of NH4Cl: the layers were separated and the organic phase washed with brine, dried over Na2SO4 and concentrated. The crude was purified by flash chromatography (hexane to hexane/ethyl acetate 9/1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With copper(l) iodide; caesium carbonate; 1,1'-bi-2-naphthol In dimethyl sulfoxide at 50℃; for 7h; Inert atmosphere; | 4.3. General procedure for synthesis of 3 and 4 General procedure: A mixture of ethyl 4-amino 3 iodo benzoate 2 (3.9 g,13.39 mmol), ethylacetoacetate or tert-butyl acetoacetate (18.75 mmol), CuI (254 mg, 1.339 mmol), BINOL (766 mg,2.67 mmol) and Cs2CO3 (4.362 g, 13.39 mmol) in dry DMSO(30 mL) was stirred at 50 C for 7 h under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and washed with a saturated solution of NH4Cl: the layers were separated and the organic phase washed with brine, dried over Na2SO4 and concentrated. The crude was purified by flash chromatography (hexane to hexane/ethyl acetate 9/1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); cesium fluoride; lithium chloride In N,N-dimethyl-formamide at 45℃; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.500 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In diethylene glycol dimethyl ether at 80℃; for 4h; | 2 Step-2: - Preparation of ethyl 4-amino-3 -(2-cyanopyrimidin-5-yl)benzoate The title compound was prepared following the procedure described in step-3 of Intermediate-33 by using 5-(4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (0.780 g,3.37 mmol), ethyl 4-amino-3-iodobenzoate (step-i of Intermediate-66, 1.17 g, 4.05 mmol),Pd(dpp/)C12(O.137 g. 0.168 minol), diglyme (10 mL), K2C03 (0.931 g, 6.74 mmol) to afford0.500 g of title product. ‘H NMR (300 MHz, DMSO-d6): 8.09-8.04 (t, J = 6.6 Hz, 1H), 7.73-7.70 (t, J = 8.1 Hz, 1H), 7.60-7.57 (t, J = 7.8 Hz, 1H), 5.03 (s, 2H), 3.30-3.19 (q, J = 7.5 Hz,4H), 1.17-1.13 (t, J= 7.5 Hz, 3H), 1.04-0.99 (t, J= 7.2 Hz, 3H); MS [M+Hj: 380:_To a solution of ethyl 4-amino-3-bromobenzoate (5.0 g, 20.66 mmol), (4- cyanophenyl)boronic acid (3.33 g, 22.72 mmol) and Pd(dppf)C12 (0.843 g, 1.03 mmoi) indiglyme (10 mL) was added K2C03 (4.27 g, 30.99 mmol). The reaction mixture was heated at80°C for 4 h. The reaction mass was quenched with water and extracted with EtOAc. The organic layer was washed with water and brine. The organic layer was separated, dried, filtered and concentrated to afford 2.7 g of title product. ‘H NMR (300 MHz, DMSO-d6): 7.92-7.89 (d, J = 7.8 Hz, 2H), 7.69-7.67 (d, J = 8.7 Hz, 1H), 7.63-7.60 (d, J = 7.8 Hz, 2H),7.56 (s, 1H), 6.8 1-6.78 (d, J = 8.4Hz, 1H), 5.83 (br s, 2H), 4.22-4.20 (q, J = 6.9 Hz, 2H),1.28-1.23 (t, J= 7.5 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); lithium chloride In N,N-dimethyl-formamide at 80℃; for 18h; Inert atmosphere; Schlenk technique; | General procedure 1: Stille cross coupling General procedure: An oven dried Schlenk tube was charged with LiCl (2.0 equiv) and heated with a heat gun under vacuum (< 0.1 mbar). After cooling to room temperature CuI (2.0 equiv), (substituted) o-iodoaniline (1.0 equiv) and Pd(PPh3)4 (5 mol%) were added and the flask was evacuatedand refilled with Ar three times. DMF (10 mL/mmol), which was previously degassed bybubbling with Ar, and the organotin compound (1.2 equiv) was added and the mixture was heated to 80 °C for 18 h. After reaching full conversion (TLC) the mixture was diluted with EtOAc and 1 M KF-solution (5 mL/mmol) was added. Upon vigorous shaking (in the Schlenktube) a colorless precipitate was formed and the mixture was filtered through a pad of Celite with EtOAc. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by (automated) flash chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); lithium chloride In N,N-dimethyl-formamide at 80℃; for 18h; Inert atmosphere; Schlenk technique; | General procedure 1: Stille cross coupling General procedure: An oven dried Schlenk tube was charged with LiCl (2.0 equiv) and heated with a heat gun under vacuum (< 0.1 mbar). After cooling to room temperature CuI (2.0 equiv), (substituted) o-iodoaniline (1.0 equiv) and Pd(PPh3)4 (5 mol%) were added and the flask was evacuatedand refilled with Ar three times. DMF (10 mL/mmol), which was previously degassed bybubbling with Ar, and the organotin compound (1.2 equiv) was added and the mixture was heated to 80 °C for 18 h. After reaching full conversion (TLC) the mixture was diluted with EtOAc and 1 M KF-solution (5 mL/mmol) was added. Upon vigorous shaking (in the Schlenktube) a colorless precipitate was formed and the mixture was filtered through a pad of Celite with EtOAc. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by (automated) flash chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium hydrogencarbonate In N,N-dimethyl-formamide at 50℃; | General procedure: An oven-dried flask was charged with o-iodoaniline (13 mmol), the corresponding benzyl bromide(10 mmol), NaHCO3 (20 mmol), and DMF (20 mL). The mixture was stirred at 50 °C under air for 3-4 h.After the completion of the reaction (monitored by TLC), the reaction mixture was cooled to ambienttemperature and 15 mL water was added to the mixture, then extracted by EtOAc for 3 times (3 × 30 mL).The combined extracts were washed with brine, dried over Na2SO4, and the solvent was removed in vacuoto provide a crude product, which was purified by column chromatography on silica gel to afford pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 3-iodobenzocaine; 4-methoxy-benzaldehyde With toluene-4-sulfonic acid In benzene for 3h; Reflux; Dean-Stark; Stage #2: With sodium cyanoborohydride; acetic acid In acetonitrile for 1h; | 2.3. Synthesis of N-PMB substituted o-iodoanilinesGeneral procedure for the benzylation of o-iodoanilines (GP1) General procedure: A solution of the respective aniline 1 (100 mmol), 4-methoxybenzaldehyde (13.6 g, 100 mmol), and TsOH (5 mg, 30 µmol) in benzene (120 mL) was heated under reflux with a Dean-Stark trap for 3 h. Benzene was then removed on a rotary evaporator and the residue was dissolved in a mixture of MeCN (40 mL) and glacial AcOH (20 mL). The resulting solution was cooled to 0 °C, NaBH3CN(2.52 g, 40.1 mmol) was then added gradually at 5-10 °C within 10 min, and stirring was continued for 1 h. The reaction mixture was worked up in two different ways. a) The reaction mixture was diluted with cold water (150 mL), and the formed precipitate was filtered off, washed with water (200 mL) and dissolved in CH2Cl2 (150 mL). The resulting solution was washed with water (100 mL), 5% NaOH (3 × 35 mL), brine (50 mL) and driedover Na2SO4. The solvents were removed, and the crude product was purified by recrystallization from a mixture of EtOAc and hexane. b) The reaction mixture was concentrated, and the residue was taken up in CH2Cl2 (150 mL). The resulting suspension was washed with water (100 mL), the 5% NaOH (3 × 35 mL), brine (50mL) and finally dried over Na2SO4. The solvents were removed, and the crude product was purified by column chromatography (eluent: hexane/EtOAc, gradient from 0 to 40% of EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: 3-iodobenzocaine With copper(l) iodide; palladium diacetate; triethylamine; triphenylphosphine In acetonitrile at 40℃; for 0.25h; Inert atmosphere; Stage #2: propargyl alcohol In acetonitrile at 25 - 40℃; for 24h; Inert atmosphere; | Ethyl 4-amino-3-(3-hydroxyprop-1-yn-1-yl)benzoate (S28) To a solution of S26 (3.49 g, 12 mmol) in CH3CN (40 mL) and Et3N (8.3 mL, 5 equiv.) underargon were added Pd(OAc)2 (135 mg, 5 mol%), PPh3 (630 mg, 20 mol%) and CuI (229 mg, 10mol%). The mixture was then stirred at 40 °C. After 15 min, propargylic alcohol (0.83 mL, 1.2equiv.) was added to the mixture and the mixture was cooled down to room temperature over24 h. The crude product was purified by LC on silica gel to give S27 (2.25 g, 86%). |
76% | Stage #1: 3-iodobenzocaine With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: propargyl alcohol In acetonitrile for 12h; Inert atmosphere; Heating; | Preparation of propargylanilines 5a-c (General method - a modified literature procedure47). General procedure: A solution ofthe appropriate aryl iodide 3,b (9 mmol) in a mixture ofEt3N (15 ml) and MeCN (15 ml) was cooled to 0°,degassed by bubbling of argon and treated by addingPdCl2(PPh3)2 (0.130 g, 0.18 mmol) and CuI (0.034 g,0.18 mmol), followed by stirring for 5 min. The reactionmixture was then treated by dropwise addition of theappropriate alkyne 4,b (10.65 mmol). The obtainedmixture was stirred at 50° for 12 h. The reaction mixturewas diluted with t, and the organic layer was washedwith saturated aqueous NH4Cl solution, saturated aqueousNaCl solution, and with H2O. The organic layer wasseparated, dried over anhydrous Na2SO4, and evaporated atreduced pressure. The obtained residue was purified by thecolumn chromatography, using a 7:1 mixture of CH2Cl2-Me2CO as eluent. Ethyl 4-amino-3-(3-hydroxyprop-1-yn-1-yl)benzoate(5).48 Yield 1.55 g (76%), brown powder. 1H NMRspectrum (CDCl3), δ, ppm: 7.99 (1H, d, J = 1.9, -2); 7.81(1H, dd, J = 8.5, J = 2.0, H-6); 6.66 (1H, d, J = 8.6, -5);4.62 (2H, s, 2(NH2)); 4.55 (2H, s, NH2(2));4.31 (2H, q, J = 7.1, O2CH2CH3); 1.89 (1H, s, OH); 1.36(3H, t, J = 7.1, O2CH2CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: 3-iodobenzocaine With hydrogenchloride; sodium nitrite In water at 0℃; Inert atmosphere; Schlenk technique; Stage #2: With sodium azide In water at 0℃; Inert atmosphere; Schlenk technique; | |
83% | Stage #1: 3-iodobenzocaine With hydrogenchloride In acetic acid methyl ester; water at 20℃; for 0.0333333h; Stage #2: With sodium nitrite In acetic acid methyl ester; water at 4℃; for 0.75h; Darkness; Stage #3: With sodium azide In acetic acid methyl ester; water at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-iodobenzocaine; acetyl chloride With potassium carbonate In dimethyl sulfoxide at 20℃; for 12h; Cooling with ice; Stage #2: allyl bromide In dimethyl sulfoxide at 20℃; for 16h; Cooling with ice; | 10 Add 2-iodoaniline (2.19 g), potassium carbonate (2.76 g), and dimethyl sulfoxide (DMSO, 50 ml) to a round bottom flask. Slowly add acetyl chloride (AcCl, 785 mg) in an ice bath. After the addition is completed, the ice bath is removed, the resulting mixed system is warmed to room temperature, and the stirring is continued for 12 hours; thereafter, allyl bromide (1.21 g) is continuously added dropwise under the ice bath. After the dropwise addition is completed, after 16 hours of reaction at room temperature, deionization is added. The reaction was quenched with water (50 ml), extracted three times with 50 ml of ether, the organic phases were combined, and the solvent was removed under reduced pressure on a rotary evaporator to obtainCrude 3-iodo-4- (N-acetyl-N-allyl) aminobenzoic acid ethyl ester (3.45 g), this product can be used for the next reaction without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 120℃; Inert atmosphere; Schlenk technique; Sealed tube; | General procedure: To a solution of 2-iodoanilines (6 mmol), 2-chlorophenylboronic acid (7.2 mmol, 1.2 equiv),Pd(PPh3)4 (346 mg, 0.30 mmol), and NaHCO3 (1.51 g, 18 mmol) in DME(1,2-Dimethoxyethane) (14mL) was stirred at room temperature for 5 min. H2O (14 mL) was added, and stirred at 120 °C for 2-8 hunder argon atmosphere. After being cooled to room temperature, the mixture was extracted withEtOAc. The extracts were combined, dried over Na2SO4, and filtered. The solvent was evaporatedunder reduced pressure and purified by column chromatography to afford the corresponding2'-chloro-[1,1'-biphenyl]-2-amine (S-1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous Sodium acetate In dimethyl sulfoxide at 80℃; for 18h; Inert atmosphere; Sealed tube; |
Tags: 62875-84-7 synthesis path| 62875-84-7 SDS| 62875-84-7 COA| 62875-84-7 purity| 62875-84-7 application| 62875-84-7 NMR| 62875-84-7 COA| 62875-84-7 structure
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