Structure of 914943-91-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 914943-91-2 |
Formula : | C13H14O2 |
M.W : | 202.25 |
SMILES Code : | O=C(OC(C)(C)C)C1=CC=CC(C#C)=C1 |
MDL No. : | MFCD25542332 |
InChI Key : | SSDAUMHJIKPITN-UHFFFAOYSA-N |
Pubchem ID : | 71743555 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
65% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 20 - 90℃; for 0.833333h; | Dichlorobis(triphenylphosphine)rhoalladium (104mg, 0.145mmol) was added in one portion to a mixture of A1.12 (1.Og, 2.48mmol), <strong>[914943-91-2]3-ethynyl-benzoic acid tert-butyl ester</strong> (753mg, 3.72mmol) and triethylamine (10ml) in DMF (7.0ml) at room temperature under a nitrogen atmosphere. The resulting mixture was heated to 90 0C for 50min before cooling to room temperature and evaporating in vacuo. The residue was purified by column chromatography using ethyl acetate:hexane as eluent to give 765mg (65%) of A72.1. Found: M+H = 478.21 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | terf-Butyl 3-ethynylbenzoate (117) (1.50 g, 9.37 mmoi) was dissolved in dry DCM (70 mL) and TFA (35.9 mL, 488 mmoi) was added carefully. The reaction was stirred at room temperature for 3 hours, concentrated in vacuo and toluene was added and then removed in vacuo to give a pale yellow solid. This material was dissolved in methanol (50 mL) and cone. H2S04 (-1 mL) was added and the resulting solution was stirred at 85 C for 20 hours. Upon cooling to room temperature, the volatiies were removed in vacuo and the residue was diluted with EtOAc (200 mL) and sat. aq. NaHCO3 (100 mL) was added slowly. The layers were separated and the aqueous layer was extracted with EtOAc (200 mL), the organic layers were combined and washed with water (100 mL), brine (100 mL), dried ( gS04), filtered and concentrated in vacuo to give the title compound (131) (1.136 g, 96% yield over 2 steps) as a pale yellow solid; 1H NMR (400 MHz, CDCI3) delta 8.17 (t, J = 1.5 Hz, 1 H), 8.03 - 8.00 (m, 1 H), 7.66 (dt, J = 7.7, 1.4 Hz, 1 H), 7.41 (td, J = 7.8, 0.4 Hz, 1 H), 3.93 (s, 3H), 3.12 (s, 1 H). LCMS Method C: rt 5.84 min. | |
rert-Butyl 3-ethynylbenzoate {117) ( .50 g, 9.37 mmol) was dissolved in dry DCM (70 mL) and TFA (35.9 mL, 468 mmol) was added carefully. The reaction was stirred at room temperature for 3 hours, concentrated in vacuo and toluene was added and then removed in vacuo to give a pale yellow solid. This material was dissolved in methanol (50 mL) and cone. H2S04 (-1 mL) was added and the resulting solution was stirred at 65 C for 20 hours. Upon cooling to room temperature, the volatiles were removed in vacuo and the residue was diluted with EtOAc (200 mL) and sat. aq. NaHC03 (100 mL) was added slowly. The layers were separated and the aqueous layer was extracted with EtOAc (200 mL), the organic layers were combined and washed with water (100 mL), brine (100 mL), dried (MgS04), filtered and concentrated in vacuo to give the title compound (131) (1.136 g, 96% yield over 2 steps) as a pale yellow solid; 'H NMR (400 MHz, CDCI3) delta 8.17 (t, J = 1.5 Hz, 1 H), 8.03 - 8.00 (m, 1 H), 7.66 (dt, J = 7.7, 1.4 Hz, 1 H), 7.41 (td, J = 7.8, 0.4 Hz, 1 H), 3.93 (s, 3H), 3.12 (s, 1 H). LCMS Method C: rt 5.84 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine; In N,N-dimethyl-formamide; at 120℃; for 0.416667h;microwave irradiation; | f-Butyl 3-ethynylbenzoate (117) ( .603 g, 7.93 mmol), 4-iodo-2-(methylthio)-5- (trifluoromethyl)pyrimidine (114) (1.647 g, 5.15 mmol), PdCI2(PPh3)2 (0.316 g, 0.45 mmol), PPh3 (0.355 g, 1 .35 mmol), Cu(l)l (0.232 g, 1 .22 mmol) and trethylamine (4.00 mL, 28.7 mmol) were combined in D F (20 mL) and the resulting mixture heated at 120 C under microwave irradiation for 25 minutes. The mixture was then concentrated under reduced pressure and purified twice using silica gel column chromatography ( 0-20% EtOAc/petroleum benzine 40-60 C then 50-100%DCM/petroleum benzine 40-60 CC) to give the title compound (118) (0.624 g, 31 %) as a yellow solid; 1H NMR (400 MHz, CDCI3) delta 8.73 (d, J = 0.8 Hz, 1 H), 8.25 (m, 1 H), 8.08 (m, 1 H), 7.78 (m, 1 H), 7.48 (m, 1 H), 2.63 (s, 3H), 1 .61 (s, 9H). |
31% | With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 120℃; for 0.416667h;Microwave irradiation; | -Butyl 3-ethynyibenzoate (117) (1.603 g, 7.93 mmol), 4-iodo-2-(methylthio)-5- (trifiuoromethyl)pyrimidine (114) (1.647 g, 5.15 mmol), PdCI2(PPh3)2 (0.316 g, 0.45 mmoi), PPh3 (0.355 g, 1.35 mmol), Cu(i)i (0.232 g, 1.22 mmol) and trethyiamine (4.00 mL, 28.7 mmoi) were combined in D F (20 mL) and the resulting mixture heated at 120 C under microwave irradiation for 25 minutes. The mixture was then concentrated under reduced pressure and purified twice using silica gel column chromatography (10-20% EtOAc/petroleum benzine 40-60 C then 50-100% DCM/petroleum benzine 40-60 C) to give the title compound (118) (0.624 g, 31 %) as a yellow solid; 1H NMR (400 MHz, CDCI3) delta 8.73 (d, J = 0,8 Hz, H), 8.25 (m, H), 8.08 (m, 1 H), 7.78 (m, 1 H), 7.48 (m, 1 H), 2.63 (s, 3H), 1.61 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | To a solution of ferf-butyl 3-((trimethylsilyl)ethynyl)benzoate (116) (4.40 g, 16.0 mmol) in THF (100 mL) at 0 C under nitrogen was added 1.0 M TBAF in THF (20.0 mL, 20.0 mmol). The mixture was then stirred at 0 C for 1 hour then 16 hours at room temperature. The mixture was then concentrated under reduced pressure, diluted with ethyl acetate (100 mL) and washed with water (3x100 mL). The organic extract was then purified using silica gel column chromatogaphy (0-5% EtOAc/petroleum benzine 40-60 C) to give the title compound (117) (2.72 g, 84%) as a pale yellow oil; 1H NMR (400 MHz, CDCI3) delta 8.09 (dd, J = 1.5, 1.5 Hz, 1 H), 7.97 (ddd, J = 7.9, 1.5, 1.5 Hz, 1 H), 7.63 (ddd, J = 7.7, 1.4, 1.4 Hz, 1 H), 7.38 (ddd, J = 7.8, 7.8, 0.5 Hz, 1H), 3.11 (s, 1 H), 1.59 (s, 9H). | |
84% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 0 - 20℃; for 17h; | To a solution of ferf-butyl 3-((trimethylsilyl)ethynyl)benzoate (116) (4.40 g, 16.0 mmol) in THF (100 mL) at 0 C under nitrogen was added 1.0 M TBAF in THF (20.0 mL, 20.0 mmo). The mixture was then stirred at 0 C for 1 hour then 16 hours at room temperature. The mixture was then concentrated under reduced pressure, diluted with ethyl acetate (100 mL) and washed with water (3x100 mL). The organic extract was then purified using silica gel column chromatogaphy (0-5% EtOAc/petroieum benzine 40-60 C) to give the title compound (117) (2.72 g, 84%) as a pale yellow oil; 1H N (400 MHz, CDCI3) delta 8.09 (dd, J = 1.5, 1.5 Hz, 1 H), 7.97 (ddd, J = 7.9, 1.5, 1.5 Hz, H), 7.63 (ddd, J = 7.7, 1.4, 1.4 Hz, 1 H), 7.38 (ddd, J = 7.8, 7.8, 0.5 Hz, 1 H), 3.11 (s, 1 H), 1.59 (s, 9H). |
A206579 [20576-82-3]
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