Structure of 886499-93-0
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CAS No. : | 886499-93-0 |
Formula : | C7H4BrF3O2 |
M.W : | 257.00 |
SMILES Code : | OC1=CC=C(Br)C(OC(F)(F)F)=C1 |
MDL No. : | MFCD06660164 |
InChI Key : | PGJZBAVEKVWHIO-UHFFFAOYSA-N |
Pubchem ID : | 17750743 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-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 |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃; for 2.0h; | Intermediate 162 To a solution of 4-bromo-3-[(trifluoromethyl)oxy]phenol (257 mg, 1.0 mmol) in dry DMF (4 mL) potassium carbonate (276 mg, 2 mmol) and then 2-chloro-5-nitropyrimidine (319 mg, 2.0 mmol) were added and the reaction mixture was stirred for 2 hours at r.t. The reaction was quenched with water (1 mL), diluted with brine (5 mL) and extracted with ethyl acetate (2x15mL). The organic layer was dried (Na2S04), filtered and evaporated to give crude 2-({4-bromo-3- [(trifluoromethyl)oxy]phenyl}oxy)-5-nitropyrimidine. This crude was dissolved in THF/water (2: 1 ) (6 mL) and Iron (279 mg, 5 mmol) and NH4CI (267,5 mg, 5 mmol) were added and the reaction mixture was stirred overnight at r.t. The solid was filtered off and the solution was diluted with an aqueous saturated solution of NaHC03 (5 mL) and extracted with ethyl acetate (2x20mL). The organic layer was dried (Na2S04), filtered and evaporated and the residue was purified by flash chromatography on silica gel (SNAP 25 g) eluting from 75:25 to 40:60 cyclohexane/ethyl acetate to afford the title compound (280 mg) as light yellow solid.H-NMR (400 MHz, DMSO-c/6): δ ppm 8.00 (2H, s), 7.81 (1 H, d), 7.34 - 7.40 (1 H, m), 7.14 (1 H, dd), 5.37 (2H, br. s.); UPLCjpqc: 1.02 min, 350 [M]+ Br pattern. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With caesium carbonate; In N,N-dimethyl-formamide; at 20.0℃; | To a mixture of <strong>[886499-93-0]4-bromo-3-(trifluoromethoxy)phenol</strong> (2.97 g, 11.6 mmol) in DMF (1 0 ml)was added Cs2C03 (5.65 g, 17.3 mmol) and benzyl chloride (1.46 ml, 12.7 mmol) at RT. The5 reaction mixture was stirred overnight then quenched with water and diluted with EtOAc. Theorganic phase was washed with water (3x), brine, dried over Na2S04 , and concentrated in vacuo.The residue was purified by flash column chromatography (EtOAc/Heptane) to afford the titlecompound as a colorless oil (3.92 g, 98% yield). 1H NMR (METHANOL-d4 ) 8 7.51 (d, J=9.1 Hz, 1 H),7.40-7.45 (m, 4H), 7.34-7.40 (m, 1 H), 6.97 (dd, J=2.5, 1.5 Hz, 1 H), 6.82 (dd, J=9.1, 3.0 Hz, 1 H),10 5.06 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
309 mg | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium fluoride; palladium diacetate; In tetrahydrofuran; water; at 70.0℃; for 7.0h; | Reference Example Compound 2 (300 mg)4-Bromo-3-trifluoromethoxyphenol (172 mg), palladium acetate (14 mg), S-phos (50 mg), potassium fluoride (106 mg) in a solution of tetrahydrofuran (6.1 mL).And water (0.040 mL) were added, and the mixture was stirred at 70 C. for 7 hours. The insoluble matter of the reaction solution was filtered off with diatomaceous earth, water was added to the filtrate, the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform: methanol = 98: 2-93: 7) to give the title compound (309 mg) as a pale yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 200.0℃; for 2.0h;Inert atmosphere; Sealed tube; Microwave irradiation; | To a solution of <strong>[886499-93-0]4-bromo-3-(trifluoromethoxy)phenol</strong> (100 mg, 0.390 mmol) in NMP (1.5 mL) was added 1-(6-chloro-3-pyridyl)-3H-imidazo[4,5-c]pyridin-2-one (Example 16, Step c) (115 mg, 0.470 mmol) and potassium carbonate (80.7 mg, 0.580 mmol). The mixture was stirred at 200 C for 2 h in a sealed tube under microwave. The mixture was combined with three other batches, and was filtered and the filtrate was purified by Prep-HPLC (FA) and lyophilized to give 1-[6-[4-bromo-3-(trifluoromethoxy)phenoxy]-3-pyridyl]-3H-imidazo[4,5-c]pyridin-2-one (40 mg, 0.090 mmol, 22% yield) as light brown solid. MS (ESI): m/z = 466.9 [M+H]+ |
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