Hydrogen Bromide → methyl 2-bromo-3-chloro-5-{N-[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]methanesulfonamido}benzoate

HRID 1424838Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1424838
N([O-])=O.[Na+].N[C:6]1[C:15]([Cl:16])=[CH:14][C:13]([N:17]([C:22]2[C:41]([CH:42]3[CH2:44][CH2:43]3)=[CH:40][C:25]3[C:26]([C:36](=[O:39])[NH:37][CH3:38])=[C:27]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[O:28][C:24]=3[CH:23]=2)[S:18]([CH3:21])(=[O:20])=[O:19])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9].[BrH:45]>C(#N)C.CCOC(C)=O.O.[Cu]Br>[Br:45][C:6]1[C:15]([Cl:16])=[CH:14][C:13]([N:17]([C:22]2[C:41]([CH:42]3[CH2:44][CH2:43]3)=[CH:40][C:25]3[C:26]([C:36](=[O:39])[NH:37][CH3:38])=[C:27]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[O:28][C:24]=3[CH:23]=2)[S:18]([CH3:21])(=[O:20])=[O:19])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Komponenten

8

Edukt 3

HCID 260Hydrogen BromideHCID 23668193Sodium NitriteHCID 122643072HCID 122643072, Verbindung

Produkt 1

HCID 122643076methyl 2-bromo-3-chloro-5-{N-[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]methanesulfonamido}benzoateAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24593copper(I) bromideKatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium nitrite (0.17 g, 2.42 mmol) was added to a 0° C. solution of methyl 2-amino-3-chloro-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)benzoate (1.29 g, 2.20 mmol) in acetonitrile (7.3 ml) and 48% aqueous HBr (7.3 ml) at 0° C. and the reaction mixture was stirred at 0° C. for 30 mins, Copper(I) bromide (0.38 g, 2.64 mmol) was added and the solution was heated at 50° C. for 30 mins. The reaction mixture was cooled to RT, diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-50% EtOAc/hexanes) to afford the title compound (1.24 g, 86%) as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86-7.93 (m, 2H), 7.50-7.63 (m, 4H), 7.17-7.25 (m, 2H), 5.79 (br. s., 1H), 3.92 (s, 3H), 3.28 (s, 3H), 3.01 (d, J=4.88 Hz, 3H), 1.94-2.04 (m, 1H), 0.76-1.09 (m, 3H), 0.55 (br. s., 1H).

Aufarbeitung

  1. temperaturethe solution was heated at 50° C. for 30 mins
  2. temperatureThe reaction mixture was cooled to RT
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by silica gel chromatography (0-50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-dbdab708817a4a8aa3c4adadb59a8c16
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927593B2

Notizen zur Reaktion

Wird geladen…