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

HRID 78770Notes

Reaction equation

HRID 78770 reaction equation
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]

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

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. LC/MS: 7.43 min, 438 (M+1)

Workup

  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

Sources & evidence

ORD record
ord-5ff4f2109f73427b86be436004c773cf
Source dataset
uspto-grants-2014_09
Patent number
US08841459B2

Reaction notes

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