Hydrogen Bromide → 5-bromo-2-(3-fluoro-4-hydroxyphenylamino)-N-phenylnicotinamide

HRID 606143Notes

Reaction equation

HRID 606143 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24]C)=[C:20]([F:26])[CH:19]=2)=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8].Br>CC(O)=O>[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([F:26])[CH:19]=2)=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 597811305-bromo-2-(3-fluoro-4-methoxyphenylamino)-N-phenylnicotinamide

Product 1

HCID 597811355-bromo-2-(3-fluoro-4-hydroxyphenylamino)-N-phenylnicotinamideYield 91%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

This process was repeated with 5-bromo-2-(3-fluoro-4-methoxyphenylamino)-N-phenylnicotinamide (2.78 g, 6.7 mmol), HOAc (7 ml), and hydrobromic acid (48%, 23 ml, 424 mmol). Both reactions were combined, and the pH of the aqueous phase was raised to above 12, and then washed with DCM. Then, the pH of the aqueous phase was lowered to 6 with concentrated HCl, and the aqueous phase was extracted with 10:1 DCM/MeOH). The organic extracts were combined and concentrated to afford the desired 5-bromo-2-(3-fluoro-4-hydroxyphenylamino)-N-phenylnicotinamide (2.45 g, 6.10 mmol, 70% purity, 52% yield). MS (ESI pos. ion) m/z: 402 (MH+, 79Br), 404 (MH+, 81Br). Calc'd exact mass for C18H13BrFN3O2: 401 (79Br), 403 (81Br).

Workup

  1. temperaturethe pH of the aqueous phase was raised to above 12
  2. washwashed with DCM
  3. extractionthe aqueous phase was extracted with 10:1 DCM/MeOH)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-63ae77092089449180833503888370ac
Source dataset
uspto-grants-2011_03
Patent number
US07915287B2

Reaction notes

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