1,4-Dioxane → 2-(4-Fluorophenyl)-N-methyl-5-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)benzofuran-3-carboxamide

HRID 555061Notes

Reaction equation

CCN(C(C)C)C(C)C.FC(F)(F)S(O[C:16]1[CH:17]=[CH:18][C:19]2[O:23][C:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)=[C:21]([C:31](=[O:34])[NH:32][CH3:33])[C:20]=2[CH:35]=1)(=O)=O.[CH3:38][C:39]1[O:43][C:42]([C:44]2[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=2)=[N:41][N:40]=1.O1CCOCC1>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:30][C:27]1[CH:26]=[CH:25][C:24]([C:22]2[O:23][C:19]3[CH:18]=[CH:17][C:16]([C:46]4[CH:47]=[CH:48][CH:49]=[C:44]([C:42]5[O:43][C:39]([CH3:38])=[N:40][N:41]=5)[CH:45]=4)=[CH:35][C:20]=3[C:21]=2[C:31]([NH:32][CH3:33])=[O:34])=[CH:29][CH:28]=1

Participants

Conditions

Temperature: 90 °C

Procedure

DIEA (50 μL, 0.288 mmol) was added to Pd(Ph3P)4 (6 mg, 4.79 μmol), 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate (40 mg, 0.096 mmol), 3-(5-methyl-1,3,4-oxadiazol-2-yl)phenylboronic acid (29 mg, 0.144 mmol). Dioxane (799 μL) and water (160 μL) was added at rt. The reaction was heated to 90° C. overnight. The mixture was cooled and purified by prep HPLC to give the titled compound (16 mg, 37%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.49-8.56 (1H, m), 8.24 (1H, s), 7.98-8.05 (4H, m), 7.93 (1H, s), 7.79-7.83 (1H, m), 7.68-7.76 (2H, m), 7.41 (2H, t, J=8.70 Hz), 2.87 (3H, d, J=4.58 Hz), 2.62 (3H, s). LC-MS retention time: 1.41 min; m/z (MH−): 426. 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. Analytical 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=12.96 min, purity=95%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 μm, Rt=11.53 min, purity=94%.

Workup

temperatureThe mixture was cooled
custompurified by prep HPLC

Sources & evidence

ORD record: ord-13649226436649a08ac9020d95dc054e
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08048887B2

Reaction notes

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