Potassium Carbonate → Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl ester

HRID 2272348Notes

Reaction equation

HRID 2272348 reaction equation
F[C:2]1[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH:15]1([C:18]2[C:19]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:20][C:21]3[O:25][C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[C:23]([C:33]([NH:35][CH3:36])=[O:34])[C:22]=3[CH:37]=2)[CH2:17][CH2:16]1.C([O-])([O-])=O.[K+].[K+]>CN(C)P(N(C)C)(N(C)C)=O.CCOC(C)=O>[CH:15]1([C:18]2[C:19]([N:38]([C:2]3[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([CH:11]=3)[C:7]([O:9][CH3:10])=[O:8])[S:39]([CH3:42])(=[O:41])=[O:40])=[CH:20][C:21]3[O:25][C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[C:23]([C:33](=[O:34])[NH:35][CH3:36])[C:22]=3[CH:37]=2)[CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 51520495-Fluoro-2-nitrobenzoic acid methyl esterHCID 160735125-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 122643071Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl esterYield 55.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 5-fluoro-2-nitrobenzoate (2.138 g, 10.73 mmol), 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (4.0 g, 9.94 mmol) and K2CO3 (4.12 g, 29.8 mmol) in hexamethylphosphoramide (25 mL) in a seal tube was stirred at 60° C. for 3 days. Cooled down to room temperature, the mixture was diluted with EtOAc and then filtered through a pad of Celite. The filtrate was washed with water and brine and dried over Na2SO4. Concentrated under reduced pressure, the residue was purified by flashing chromatography on silica gel eluted with 0-50% EtOAc in hexane to give the product (3.2 g, 55%) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.00 (d, J=9.17 Hz, 1H) 7.89 (dd, J=8.78, 5.27 Hz, 2H) 7.55 (d, J=9.37 Hz, 2H) 7.50 (dd, J=9.07, 2.63 Hz, 1H) 7.44 (d, J=2.73 Hz, 1H) 7.23 (t, J=8.68 Hz, 2H) 5.81 (d, J=4.49 Hz, 1H) 3.91 (s, 3H) 3.35 (s, 3H) 3.02 (d, J=4.88 Hz, 3H) 1.86-1.96 (m, 1H) 0.97-1.05 (m, 1H) 0.89 (br. s., 2H) 0.59 (br. s., 1H). LCMS (m/z, ES+)=582 (M+H+).

Workup

  1. temperatureCooled down to room temperature
  2. filtrationfiltered through a pad of Celite
  3. washThe filtrate was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentrated under reduced pressure
  6. customthe residue was purified
  7. washeluted with 0-50% EtOAc in hexane

Sources & evidence

ORD record
ord-6b33c40235ea4822a748a43905af721e
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

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