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

HRID 1424852Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1424852
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

Komponenten

6

Edukt 3

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

Produkt 1

HCID 122643071Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl esterAusbeute 55,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 12679HexamethylphosphoramideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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+).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5d02c982bacd442f9cced53537e1ab57
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927593B2

Notizen zur Reaktion

Wird geladen…