Benzyl Bromide → 5-(3-(2-Benzyl-2H-tetrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1877554Notes

Reaction equation

HRID 1877554 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:9]1[C:13]([C:14]2[CH:15]=[C:16]([C:20]3[CH:21]=[CH:22][C:23]4[O:27][C:26]([C:28]5[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=5)=[C:25]([C:35]([NH:37][CH3:38])=[O:36])[C:24]=4[CH:39]=3)[CH:17]=[CH:18][CH:19]=2)=[N:12][N:11]=[N:10]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[CH2:1]([N:10]1[N:11]=[N:12][C:13]([C:14]2[CH:15]=[C:16]([C:20]3[CH:21]=[CH:22][C:23]4[O:27][C:26]([C:28]5[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=5)=[C:25]([C:35]([NH:37][CH3:38])=[O:36])[C:24]=4[CH:39]=3)[CH:17]=[CH:18][CH:19]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10340Sodium CarbonateHCID 178485244HCID 178485244, compound

Product 1

HCID 592757125-(3-(2-Benzyl-2H-tetrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 19.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Benzyl bromide (29 μL, 0.242 mmol) was added to a stirring solution of 5-(3-(1H-tetrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (50 mg, 0.121 mmol) and Na2CO3 (26 mg, 0.242 mmol) in DMF (1.2 mL) at 100° C. It was allowed to stir overnight. 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 (12 mg, 19%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.48-8.56 (1H, m), 8.30-8.35 (1H, m), 8.06 (1H, d, J=7.63 Hz), 7.98-8.03 (2H, m), 7.90-7.93 (2H, m), 7.78-7.83 (1H, m), 7.72-7.77 (1H, m), 7.69 (1H, t, J=7.78 Hz), 7.36-7.46 (7H, m), 6.04 (2H, s), 2.86 (3H, d, J=4.58 Hz). LC-MS retention time: 1.78 min; m/z (MH+): 504. 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 Sunfire C-18, 4.6×150 mm, 3.5 μm, Rt=15.69 min, purity=97%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 μm, Rt=13.95 min, purity=98%.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative reverse phase HPLC on a C18 column
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-9892880934a347f29fc6e552b91af863
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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