1,2-Dichloroethane → 5-(3-(tert-Butylsulfonylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 555082Notes

Reaction equation

HRID 555082 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:22]=[C:23]([CH:27]=[CH:28][CH:29]=4)[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.[C:42]([S:46]([NH2:49])(=[O:48])=[O:47])([CH3:45])([CH3:44])[CH3:43].ClCCCl>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:42]([S:46]([NH:49][C:24]([C:23]1[CH:22]=[C:21]([C:18]2[CH:19]=[CH:20][C:10]3[O:9][C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[C:12]([C:13]([NH:14][CH3:15])=[O:16])[C:11]=3[CH:17]=2)[CH:29]=[CH:28][CH:27]=1)=[O:25])(=[O:48])=[O:47])([CH3:45])([CH3:44])[CH3:43]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2757335tert-ButylsulfonamideHCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

Product 1

HCID 592751895-(3-(tert-Butylsulfonylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 31%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

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 tert-butylsulfonamide (37 mg, 0.27 mmol). 1,2-Dichloroethane (1 mL) and DMF (0.3 mL) were added, the vial was capped, and the reaction was stirred at r.t. overnight. The reaction was concentrated, filtered, purified by prep HPLC, and concentrated on a SPEEDVAC® to give 14 mg (31% yield) of the title compound as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 8.12 (s, 1H) 7.97 (s, 1H) 7.91 (dd, J=8.55, 5.19 Hz, 2H) 7.84 (d, J=7.63 Hz, 1H) 7.79 (d, J=7.32 Hz, 1H) 7.46-7.59 (m, 3H) 7.19 (t, J=8.55 Hz, 2H) 6.04 (br. s., 1H) 2.99 (d, J=4.58 Hz, 3H) 1.54 (s, 9H). 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=1.71 min, (ES+) m/z (MH+)=509. 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=16.49 min, purity=100%; column: Waters XBridge phenyl 4.6×150 mm, 3.5 μm, Rt=15.35 min, purity=100%.

Workup

  1. customthe vial was capped
  2. stirringthe reaction was stirred at r.t. overnight
  3. concentrationThe reaction was concentrated
  4. filtrationfiltered
  5. custompurified by prep HPLC
  6. concentrationconcentrated on a SPEEDVAC®

Sources & evidence

ORD record
ord-41c97d7af23e462fa0bb8a90c11456fb
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

Loading…