2-Fluoro-4-iodoaniline → HCID 25070856, compound

HRID 559063Notes

Reaction equation

HRID 559063 reaction equation
[Li+].CC([N-]C(C)C)C.[F:9][C:10]1[CH:16]=[C:15]([I:17])[CH:14]=[CH:13][C:11]=1[NH2:12].[CH:18]1([N:21]2[C:30]3[C:25](=[C:26](F)[CH:27]=[C:28]([F:31])[CH:29]=3)[C:24](=[O:33])[C:23]([OH:34])=[C:22]2[CH3:35])[CH2:20][CH2:19]1>C1COCC1>[CH:18]1([N:21]2[C:30]3[C:25](=[C:26]([NH:12][C:11]4[CH:13]=[CH:14][C:15]([I:17])=[CH:16][C:10]=4[F:9])[CH:27]=[C:28]([F:31])[CH:29]=3)[C:24](=[O:33])[C:23]([OH:34])=[C:22]2[CH3:35])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2724682Lithium diisopropylamideHCID 57687364HCID 57687364, compound

Product 1

HCID 25070856HCID 25070856, compoundYield 20.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LDA (2N solution in heptane/tetrahydrofuran/ethylbenzene, 6 mL, and 12 mmol) was added dropwise to a stirred solution of 2-fluoro-4-iodoaniline (2.085 g, 8.8 mmol) in THF (14 mL) at −78° C. After 10 minutes, a solution of example 6c (0.9 g, 3.57 mmol) in THF (30 mL) was then added at −78° C. The reaction mixture was allowed to warm to room temperature and stirred for 13 h. The solution was cooled to 0° C., quenched with 1N HCl (100 mL), extracted with EtOAc and dried (MgSO4). Purification by silica gel chromatography (10% MeOH/DCM) gave 340 mg (20%) of the title compound as light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 12.72 (s, 1H), 8.41 (s, 1H), 7.73 (dd, 1H, J=10.4, 1.6 Hz), 7.55 (dd, 1H. J=8.4, 1.6 Hz), 7.49 (t, 1H, J=8.4 Hz), 7.03 (dd, 1H, J=10.4, 1.6 Hz), 6.62 (dd, 1H, J=10.4, 1.6 Hz), 3.32-3.42 (m, 1H), 2.54-2.53 (m, 3H), 1.35-1.42 (m, 2H), 0.84-0.89 (m, 2H). MS (ES) [m+H] calc'd for C19H15F2IN2O2, 469; found 469.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. customquenched with 1N HCl (100 mL)
  3. extractionextracted with EtOAc
  4. dry with materialdried (MgSO4)
  5. customPurification by silica gel chromatography (10% MeOH/DCM)

Sources & evidence

ORD record
ord-dc1ef0019990485c8070dc2503ad5909
Source dataset
uspto-grants-2011_11
Patent number
US08063066B2

Reaction notes

Loading…