613-92-3 → HCID 59275502, compound

HRID 555063Notes

Reaction equation

HRID 555063 reaction equation
C[O-].[Na+].[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[CH:23]=[CH:22][C:21]([C:24]4[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=4)[C:27](OC)=[O:28])=[CH:20][C:14]=3[C:15]=2[C:16](=[O:19])[NH:17][CH3:18])=[CH:7][CH:6]=1.O/[N:35]=[C:36](\[NH2:43])/[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CCO>[F:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[O:12][C:13]3[CH:23]=[CH:22][C:21]([C:24]4[CH:33]=[CH:32][CH:31]=[C:26]([C:27]5[O:28][N:43]=[C:36]([C:37]6[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=6)[N:35]=5)[CH:25]=4)=[CH:20][C:14]=3[C:15]=2[C:16]([NH:17][CH3:18])=[O:19])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 7259353613-92-3HCID 10942334Sodium MethoxideHCID 59275138Methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoate

Product 1

HCID 59275502HCID 59275502, compoundYield 14.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium methoxide (33 mg, 0.620 mmol) was added to a stirring slurry of methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoate (50 mg, 0.124 mmol) and (Z)-N′-hydroxybenzimidamide (51 mg, 0.372 mmol) in EtOH (2.5 mL) at rt. The mixture was subjected to microwave irradiation for 5 min at 160° C. The mixture was concentrated and purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (8.7 mg, 14%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.49-8.56 (1H, m), 8.44-8.49 (1H, m), 8.19-8.25 (1H, m), 8.13-8.18 (2H, m), 8.07-8.12 (1H, m), 8.00-8.07 (2H, m), 7.98 (1H, s), 7.76-7.86 (3H, m), 7.59-7.68 (3H, m), 7.41 (2H, t, J=8.91 Hz), 2.88 (3H, d, J=4.77 Hz). LC-MS retention time: 1.94 min; m/z (MH+): 490. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u 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 Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=17.39 min, purity=99%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 mm, Rt=14.58 min, purity=98%.

Workup

  1. customirradiation for 5 min at 160° C
  2. concentrationThe mixture was concentrated
  3. custompurified by preparative reverse phase HPLC on a C18 column
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-434fcf93a05e41589668d1d70a370e08
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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