N-Methylbenzenesulfonamide → 2-(4-Fluorophenyl)-N-methyl-5-(3-(phenylsulfonylcarbamoyl)phenyl)benzofuran-3-carboxamide

HRID 1877587Notes

Reaction equation

HRID 1877587 reaction equation
O1C2C=CC=CC=2C(C(N)=O)=C1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][C:22]3[CH:32]=[CH:31][C:30]([C:33]4[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=4)[C:36](O)=[O:37])=[CH:29][C:23]=3[C:24]=2[C:25](=[O:28])[NH:26][CH3:27])=[CH:16][CH:15]=1.CCN=C=NCCCN(C)C.Cl.C[NH:55][S:56]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)(=[O:58])=[O:57]>CN(C1C=CN=CC=1)C.CN(C=O)C.ClCCCl>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][C:22]3[CH:32]=[CH:31][C:30]([C:33]4[CH:41]=[CH:40][CH:39]=[C:35]([C:36](=[O:37])[NH:55][S:56]([C:59]5[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=5)(=[O:58])=[O:57])[CH:34]=4)=[CH:29][C:23]=3[C:24]=2[C:25]([NH:26][CH3:27])=[O:28])=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 78858N-MethylbenzenesulfonamideHCID 5952331-Benzofuran-3-carboxamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

Product 1

HCID 592751942-(4-Fluorophenyl)-N-methyl-5-(3-(phenylsulfonylcarbamoyl)phenyl)benzofuran-3-carboxamideYield 56.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-fluorophenyl)-N-methyl-5-(3-(methyhphenylsulfonyl)carbamoyl)phenyl)benzofuran-3-carboxamide. In a 1 dram vial with stir bar were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (35 mg, 0.090 mmol), DMAP (33 mg, 0.27 mmol), EDC hydrochloride (26 mg, 0.14 mmol), and N-methylbenzenesulfonamide (50 μL, 0.26 mmol). 1,2-Dichloroethane (0.5 mL) and DMF (0.5 mL) were added, the vial was capped, and the reaction was stirred at r.t. overnight. The reaction was filtered, purified by prep HPLC, and concentrated on a speedvac to give 27 mg (55% yield) of the title compound as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 7.91-8.02 (m, 5H) 7.75-7.82 (m, 2H) 7.65 (t, J=7.48 Hz, 1H) 7.47-7.60 (m, 6H) 7.15-7.24 (m, 2H) 5.91 (d, J=4.27 Hz, 1H) 3.36 (s, 3H) 3.04 (d, J=4.88 Hz, 3H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, Solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.89 min, (ES+) m/z (MH+)=543. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: Phenomenex Gemini C18, 4.6 mm, 3 μm, Rt=17.42 min, purity=92%; column: Waters Xbridge Phenyl 4.6×150 mm, 3.5 μm, Rt=17.86 min, purity >90%.

Workup

  1. customthe vial was capped
  2. stirringthe reaction was stirred at r.t. overnight
  3. filtrationThe reaction was filtered
  4. custompurified by prep HPLC
  5. concentrationconcentrated on a speedvac

Sources & evidence

ORD record
ord-554130cce2e94468bb973c606af17628
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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