Isopropyl iodide → 2-(4-Fluorophenyl)-5-(3-(2-isopropyl-2H-tetrazol-5-yl)phenyl)-N-methylbenzofuran-3-carboxamide

HRID 1671886Notes

Reaction equation

HRID 1671886 reaction equation
I[CH:2]([CH3:4])[CH3:3].[NH:5]1[C:9]([C:10]2[CH:11]=[C:12]([C:16]3[CH:17]=[CH:18][C:19]4[O:23][C:22]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)=[C:21]([C:31]([NH:33][CH3:34])=[O:32])[C:20]=4[CH:35]=3)[CH:13]=[CH:14][CH:15]=2)=[N:8][N:7]=[N:6]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:24]([C:22]2[O:23][C:19]3[CH:18]=[CH:17][C:16]([C:12]4[CH:13]=[CH:14][CH:15]=[C:10]([C:9]5[N:8]=[N:7][N:6]([CH:2]([CH3:4])[CH3:3])[N:5]=5)[CH:11]=4)=[CH:35][C:20]=3[C:21]=2[C:31]([NH:33][CH3:34])=[O:32])=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 10340Sodium CarbonateHCID 178485244HCID 178485244, compound

Product 1

HCID 592757522-(4-Fluorophenyl)-5-(3-(2-isopropyl-2H-tetrazol-5-yl)phenyl)-N-methylbenzofuran-3-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-iodopropane (29 mg, 0.169 mmol) was added to a stirring solution of 5-(3-(1H-tetrazol-5-yl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (35 mg, 0.085 mmol) and Na2CO3 (18 mg, 0.169 mmol) in DMF (1 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, 30%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.49-8.57 (1H, m), 8.34 (1H, s), 8.08 (1H, d, J=7.32 Hz), 7.99-8.05 (2H, m), 7.87-7.94 (2 H, m), 7.79-7.83 (1H, m), 7.72-7.78 (1H, m), 7.70 (1H, t, J=7.78 Hz), 7.41 (2H, t, J=8.70 Hz), 5.17-5.27 (1H, m), 2.87 (3H, d, J=4.58 Hz), 1.66 (6H, d, J=6.71 Hz). LC-MS retention time: 2.02 min; m/z (MH+): 456. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u 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=15.35 min, purity=96%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 μm, Rt=13.39 min, purity=97%.

Workup

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

Sources & evidence

ORD record
ord-e0ea2f6fa7b347c3a78aa9aa5e5a2afb
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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