Trifluoroacetic acid → N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

HRID 1482667Notes

Reaction equation

HRID 1482667 reaction equation
[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])[CH:26]=[CH:27][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15]COCCOC)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl.CO>[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])[CH:26]=[CH:27][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86724330N-(3-((5-fluoro-2-((4-((2-methoxyethoxy)methoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

Product 1

HCID 86724331N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamideYield 6.9%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

In a 25 mL 3-neck RBF equipped with a rubber septum, N-(3-((5-fluoro-2-((4-((2-methoxyethoxy)methoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide (0.180 g) was taken and TFA (1.0 mL) was added drop wise at room temperature under stirring. The reaction mixture was further stirred for 30 min. Completion of reaction was monitored by TLC using CHCl3:MeOH (9.5:0.5). After completion, the reaction mixture was quenched in water. The aqueous solution was basified with saturated sodium bicarbonate solution. The product was extracted into DCM, washed with water and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The crude product was treated with DBU and 75 mg of product was collected. This was further purified by preparative TLC using CHCl3:MeOH (9.5:0.5) as a mobile phase to give 10 mg of N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide. M+1=365.9 1H NMR: DMSO-d6 (400 MHz) 5.73-5.76 (dd, 1H, J=2, 8), 6.23-6.28 (dd, 1H, J=2, 18.8), 6.48-6.55 (m, 1H), 6.59. 6.61 (d, 2H, J=8.8), 7.22-7.261 (t, 1H, J=8.16), 7.40-7.51 (m, 4H), 8.03-8.04 (d, 2H, J=3.6), 8.426 (s, 1H), 8.902 (s, 1H), 9.331 (s, 1H), 10.26 (s, 1H).

Workup

  1. stirringThe reaction mixture was further stirred for 30 min
  2. customCompletion of reaction
  3. customAfter completion, the reaction mixture was quenched in water
  4. extractionThe product was extracted into DCM
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. additionThe crude product was treated with DBU and 75 mg of product
  9. customwas collected
  10. customThis was further purified by preparative TLC

Sources & evidence

ORD record
ord-cd9cbb8eb82f4c88868b6e5ee239718e
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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