Cesium carbonate → HCID 178470382, compound

HRID 1877576Notes

Reaction equation

HRID 1877576 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[C:13]1[CH:14]=[CH:15][C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[C:18]([C:28](=[O:31])[NH:29][CH3:30])[C:17]=2[CH:32]=1)(=O)=O.[CH3:35][C:36]1[N:37]=[C:38]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48](B3OC(C)(C)C(C)(C)O3)[CH:47]=2)[NH:39][C:40]=1[C:41]([O:43][CH2:44][CH3:45])=[O:42].O1CCOCC1>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[O:20][C:16]3[CH:15]=[CH:14][C:13]([C:50]4[CH:51]=[C:46]([C:38]5[NH:39][C:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])=[C:36]([CH3:35])[N:37]=5)[CH:47]=[CH:48][CH:49]=4)=[CH:32][C:17]=3[C:18]=2[C:28](=[O:31])[NH:29][CH3:30])=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 59275663(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonateHCID 178470381HCID 178470381, compound

Product 1

HCID 178470382HCID 178470382, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Cesium carbonate (234 mg, 0.719 mmol) was added to Pd(Ph3P)4 (27.7 mg, 0.024 mmol), 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate (200 mg, 0.479 mmol), ethyl 4-methyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazole-5-carboxylate (171 mg, 0.479 mmol). Dioxane (4 mL) and water (800 μL) was added at rt. The reaction was heated to 90° C. overnight. The mixture was diluted with ethyl acetate and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the titled compound (6.8 mg, 3%). 1H NMR (500 MHz, DMSO-d6) d ppm 13.16 (0.34H, s), 12.96 (0.66H, s), 8.54 (1H, q, J=4.48 Hz), 8.50 (0.32H, s), 8.24 (0.68H, s), 8.10 (0.31H, d, J=7.93 Hz), 7.97-8.04 (2H, m), 7.89-7.97 (2H, m), 7.79-7.84 (1.35H, m), 7.70-7.79 (2H, m), 7.54-7.63 (1H, m), 7.37-7.44 (2H, m), 4.33 (0.65H, q, J=7.22 Hz), 4.25 (1.42H, q, J=7.22 Hz), 2.87 (3H, d, J=4.88 Hz), 2.55 (2H, s), 2.45 (1H, s), 1.34 (1H, t, J=7.02 Hz), 1.31 (2H, t, J=7.17 Hz). LC-MS retention time: 1.46 min; m/z (MH+): 498. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5 u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 mm, Rt=9.90 min, purity=99%.

Workup

  1. washwashed
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

Sources & evidence

ORD record
ord-47923886ce0040fc879af77403373e54
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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