2-Fluoro-4-iodoaniline → 2-Bromo-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid

HRID 39509

Reaktionsgleichung

C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:11][C:12]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:13]=1[NH2:14].[Br:20][C:21]1[CH:22]=[C:23]([C:27](F)=[CH:28][N:29]=1)[C:24]([OH:26])=[O:25]>C1COCC1.CCOC(C)=O>[Br:20][C:21]1[CH:22]=[C:23]([C:27]([NH:14][C:13]2[CH:15]=[CH:16][C:17]([I:19])=[CH:18][C:12]=2[F:11])=[CH:28][N:29]=1)[C:24]([OH:26])=[O:25]

Komponenten

Reaktionsbedingungen

Temperatur: -78 °C

Versuchsvorschrift

Lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (11.9 ml, 1.00 M, 11.82 mmol) was added to a solution of 2-fluoro-4-iodoaniline (1.40 g, 5.91 mmol) at −78° C. The pale green colored solution was stirred for 1½ h at −78° C. Then, lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (5.45 ml, 1.00 M, 5.45 mmol) was added followed by 2-bromo-5-fluoroisonicotinic acid (1.00 g, 4.55 mmol) in THF (5 ml). The dark colored homogeneous mixture was warmed to room temperature and stirred overnight. The crude was diluted with EtOAc (300 ml). Then, it washed with dilute HCl solution (20 ml), H2O (20 ml), dried and purified on Flashmaster II using a 100 g cartridge to obtain 1.18 g (59%) of 2-Bromo-5-(2-fluoro-4-iodo-phenylamino)-isonicotinic acid.

Aufarbeitung

temperatureThe dark colored homogeneous mixture was warmed to room temperature
stirringstirred overnight
washThen, it washed with dilute HCl solution (20 ml), H2O (20 ml)
customdried
custompurified on Flashmaster II

Quellen und Nachweise

ORD-Eintrag: ord-e2bb8318f0b948d7804f0b05b647a69b
Quelldatensatz: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08524911B2

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