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CAS No. : | 959992-62-2 | MDL No. : | MFCD09834129 |
Formula : | C7H7BrN2O | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | OTGDCHNSXQUISE-UHFFFAOYSA-N |
M.W : | 215.05 | Pubchem ID : | 20824376 |
Synonyms : |
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | |
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 |
---|---|---|
55% | To a solution of 6-bromo-3-(2-bromoethoxy)-2-nitropyridine (4.5 g, 13.8 mmol) in glacial acetic acid (23 ml) was added iron (powder, 3.08 g, 55.2 mmol) in one portion. The reaction mixture was heated to 90C during 5 hours, then cooled down, diluted in ethyl acetate and filtered through a silica gel plug using ethyl acetate as eluent. After evaporation, the residue was dissolved in DMF (50 ml). Potassium carbonate (5.72 g, 41.4 mmol) was added and the mixture was heated to 90C for 2 hours, then to 70C overnight. After evaporation of solvent, the residue was dissolved in DCM, salts were removed by filtration, and the crude compound was purified by silica gel flash chromatography (30 to 50% ethyl acetate in petroleum ether) to give 6-bromo-3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazine as a pale yellow oil (1.64 g, 55%); Mass Spectrum [M+H]+ = 215; 1H NMR Spectrum (CDC13) 3.54-3.60 (m, 2H), 4.19 (t, 2H), 5.35 (bs, IH), 6.66 (d, IH), 6.82 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 120℃; for 3h;Micrawave irradiation; | A Smith process vial was charged with a stir bar, compound 54B (0.33 g, 1.54 mmol), CuCN (0.276 g, 3.08 mmol) and DMF (3 mL). The reaction vessel was sealed and heated to 120 C. for 3 h under microwave irradiation. After cooling, the reaction mixture was transferred to a round bottom flask and concentrated under vacuum. Compound 55A was obtained quantitatively by continuous extraction with EtOAc in a Soxlet apparatus. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 50℃; | 6-bromo-3,4-dihydro-2H-pyrido[3,2-b] [l ,4]oxazine (5; 2.0 g, 9.30 mmol), 3-(trifluromethyl)- phenylboronic acid (2.65 g, 1 3.95 mmol), Pd(Ph3)4 (21 5 mg, 0. 186 mmol) and CsCO3 (6.0 g, 18.6 mmol) were all dissolved in dioxane:H20 mixture (45 mL: l mL) and heated to 50 C overnight. Product peak seen by LCMS, but some starting material remained, added more boronic acid and stirred at 50 C overnight. The starting material peak was unchanged, cooled to room temp and some precipitates started to crash out. Diluted with water (40 mL), extracted with EtOAc (3 x 40 mL), washed with brine, dried over MgS04, filtered, concentrated and purified through I SCO silica column (0 to 100% EtOAc/pentanes) to collect mixed fractions of 6-(3-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][ l ,4]oxazine (6) M S (ESI) calcd for C 14H1 1 F3N2O (m/z) 280.08, found 281 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; | To a solution of 6-bromo-3-(2-bromoethoxy)-2-nitropyridine (3; 560 mg, 1 .73 mmol) in glacial acetic acid (6 mL) was added Fe (387 mg, 6.91 mmol) in one portion. The reaction mixture was heated at 90 C for 5 h, then cooled down, di luted in EtOAc and filtered through a silica plug using EtOAc as the eluent. After evaporation of the AcOH, the residue 4 was dissolved in DMF (5 mL), 2CO3 (716 mg, 5. 19 mmol) was added and the mixture was heated to 90 C overnight. In general, the solvent was concentrated and the mixture was purified by silica gel chromatography to afford 6-bromo-3,4-dihydro-2H-pyrido[3,2- b][l ,4]oxazine (5; 185 mg, 50%). MS (ESI) calcd for C7H7BrN20 (m/z): 21 3.97. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine; In N,N-dimethyl-formamide; at 25℃; for 24h; | Step 5 To a solution of Compound (10) (2.50 g, 11.6 mmol) in dimethylformamide (20 mL), triethylamine (4.8 mL), 34.9 mmol) and phenylisocyanate (1.6 mL, 15.1 mmol) were added. The solution was then stirred at 25 C for 24 hours. Water (3.0 mL) was then added to the reaction solution. The precipitated powder was filtered, washed with water, and then dried to yield subject compound I-113 (3.4 g, 85%) as a pale brown powder.1H-NMR (DMSO-d6) delta11.92 (1H, s), 7.52-7.55 (2H, m), 7.34-7.40 (3H, m), 7.28 (1H, dd, J = 8.4 Hz, J = 1.5 Hz), 4.30 (2H, t, J = 4.8 Hz), 4.04 (2H, t, J = 4.8 Hz) LC/MS (Method A): 2.45 min, [M+H]+ = 334.0. |
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