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

HRID 39509

반응식

HRID 39509 반응식
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]

참가 물질

6

반응물 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium Hexamethyldisilazide2회HCID 467392772-Bromo-5-fluoroisonicotinic acid

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e2bb8318f0b948d7804f0b05b647a69b
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524911B2

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