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Chemical Structure| 676445-27-5 Chemical Structure| 676445-27-5

Structure of 676445-27-5

Chemical Structure| 676445-27-5

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Product Details of [ 676445-27-5 ]

CAS No. :676445-27-5
Formula : C7H5FINO
M.W : 265.02
SMILES Code : O=C(N)C1=C(I)C=CC=C1F
MDL No. :MFCD18396919

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Application In Synthesis of [ 676445-27-5 ]

* 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.

  • Downstream synthetic route of [ 676445-27-5 ]

[ 676445-27-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 111771-08-5 ]
  • [ 676445-27-5 ]
YieldReaction ConditionsOperation in experiment
[0184] To a solution of <strong>[111771-08-5]2-fluoro-6-iodobenzoic acid</strong> (10.0 g, 37.6 mmol) in 100 mL CH2Cl2 containing a catalytic amount of DMF, oxalyl chloride (6.20 g, 48.9 mmol) was added drop-wise. The solution was stirred at room temperature 30 minutes, and concentrated under vacuum. The residue was dissolved in 100 mL CH2Cl2 and saturated 3× with ammonia gas. The suspension was concentrated under vacuum to yield 2-fluoro-6-iodobenzamide as a white solid with a mass ion (ES+) of 266.4 for M+H+. [0185] A solution of the above residue (11.5 g, 43.4 mmol) in N,N-dimethyl-acetamide dimethyl acetal (17.34 g, 130.2 mmol) was heated to 100 C. for 3 hours. The solution was concentrated under vacuum. Hydroxylamine hydrochloride (3.62 g, 52.1 mmol), 5N NaOH (10.4 mL, 52.1 mmol), 70% acetic acid (40 mL), and dioxane (40 mL) were combined and added to the above residue. The mixture was heated to 90 C. for 1 hour, cooled to room temperature, and concentrated under vacuum. The residue was diluted with EtOAc, washed with aqueous sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 0-10% ethyl acetate in hexanes to afford 5-(2-fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole as a pale yellow solid with a mass ion (ES+) of 305.4 for M+H+. [0186] A mixture of 4-chloro-N-2-{(1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}pyridine-2,3-diamine (0.200 g, 0.535 mmol), 5-(2-fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole (0.179 g, 0.59 mmol), potassium carbonate (0.185 g, 1.34 mmol), tri-ortho-tolylphosphine (0.007 g, 0.02 mmol), and palladium acetate (3.0 mg, 0.01 mmol) in 4 mL of THF and 0.05 mL of water was heated in a sealed flask at 100 C. overnight. The mixture was then cooled and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 0-20% ethyl acetate and hexane to provide 4-chloro-N2-{(1R)-1-[3'-fluoro-2'-(3-methyl-1,2,4-oxadiazol-5-yl)-1-1,1'-biphenyl-4-yl]ethyl}pyridine-2,3-diamine with a mass ion (ES+) of 424.58 for M+H+(35Cl). [0187] To a solution of the above compound (0.050 mg, 0.12 mmol), 3,3,3-trifluoropropionic acid, (0.030 g, 0.24 mmol), 1-ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.045 g 0.24 mmol), 1-hydroxy-7-azabenzotriazole (0.023 g, 0.34 mmol) was added triethylamine (0.048 g, 0.47 mmol). The resulting solution was stirred at room temperature for 24 h, and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was subjected to silica gel chromatography eluted with 0-30% ethyl acetate in hexanes to provide the title compound that gave a proton NMR spectrum consistent with theory and a mass ion (ES+) of 534.6 for M+H+(35Cl): 1H NMR (300 MHz, MeOH-d4) delta 7.81 (dd, J=5.6, 2.0 Hz, 1H), 7.75-7.67 (m, 1H), 7.39-7.30 (m, 4H), 7.12-7.09 (m, 2H), 6.68 (dd, J=5.4, 2.0 Hz, 1H), 5.25 (q, J=7.1 Hz, 1H), 3.32 (q, J=1.5 Hz, 2H), 2.33 (s, 3H), 1.53 (d, J=7.1 Hz, 3H).
 

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