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

HRID 39509

反応式

HRID 39509 の反応式
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]

参加物

6

反応物 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium Hexamethyldisilazide2 回HCID 467392772-Bromo-5-fluoroisonicotinic acid

生成物 1

HCID 576496492-Bromo-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid収率 59.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-e2bb8318f0b948d7804f0b05b647a69b
出典データセット
uspto-grants-2013_09
特許番号
US08524911B2

関連ノート

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