HCID 59275466, compound → HCID 59275296, compound

HRID 1877545Notes

Reaction equation

HRID 1877545 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27](=[O:38])[NH:28][C:29]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)([CH3:31])[CH3:30])[CH:22]=4)=[C:17]([N+:39]([O-])=O)[C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1>C(O)C.CC(O)=O.CCOC(C)=O.[Fe]>[NH2:39][C:17]1[C:11]2[C:12]([C:13]([NH:15][CH3:16])=[O:14])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[O:9][C:10]=2[CH:20]=[CH:19][C:18]=1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27](=[O:38])[NH:28][C:29]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)([CH3:31])[CH3:30])[CH:22]=1

Participants

6

Reactant 1

HCID 59275466HCID 59275466, compound

Product 1

HCID 59275296HCID 59275296, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Iron (25 mg, 0.453 mmol) was added to a stirring solution of 2-(4-fluorophenyl)-N-methyl-4-nitro-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxamide (50 mg, 0.091 mmol) in ethanol (1 mL) and AcOH (1 mL) at rt. It was placed in a reaction block set to 100° C. It was allowed to stir for 1 hr. The mixture was allowed to cool and was diluted with EtOAc and washed with 1M HCl, followed by 1N NaOH and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and triturated with Et2O to give the titled compound (28 mg, 56%). 1H NMR (300 MHz, CD3OD) δ ppm 7.83-7.89 (1H, m), 7.73-7.81 (3H, m), 7.52-7.64 (2H, m), 7.42-7.49 (2H, m), 7.10-7.35 (6H, m), 6.98 (1H, d, J=8.42 Hz), 2.87 (3H, s), 1.76 (6H, s). LC-MS retention time: 2.33 min; m/z (MH+): 522. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10 u C18 3.0×50 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 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. 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 μm, Rt=14.17 min, purity=97%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 μm, Rt=12.84 min, purity=98%.

Workup

  1. customset to 100° C
  2. temperatureto cool
  3. washwashed with 1M HCl
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customtriturated with Et2O

Sources & evidence

ORD record
ord-20f168aa97154b24b61289fb7c4b441d
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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