4-Aminoacetanilide → N-[4-(3,5-dichloro-2,6-difluoro-pyridin-4-ylamino)-phenyl]-acetamide

HRID 1354824Notes

Reaction equation

HRID 1354824 reaction equation
[Cl:1][C:2]1[C:3]([F:11])=[N:4][C:5]([F:10])=[C:6]([Cl:9])[C:7]=1F.[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:22])[CH3:21])=[CH:15][CH:14]=1.C(N(C(C)C)C(C)C)C>CN1C(=O)CCC1.CCOC(C)=O>[Cl:1][C:2]1[C:3]([F:11])=[N:4][C:5]([F:10])=[C:6]([Cl:9])[C:7]=1[NH:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20](=[O:22])[CH3:21])=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 312304-AminoacetanilideHCID 612733,5-Dichloro-2,4,6-trifluoropyridineHCID 81531Diisopropylethylamine

Product 1

HCID 21104058N-[4-(3,5-dichloro-2,6-difluoro-pyridin-4-ylamino)-phenyl]-acetamideYield 58%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3,5-Dichloro-2,4,6-trifluoro-pyridine (136) (1 g, 4.95 mmol) and N-(4-Amino-phenyl)-acetamide (137) (0.743 g, 4.95 mmol) were dissolved in NMP (12 mL), iPr2EtN (9.9 mmol) was added and the mixture was shaken at room temperature for 5 hours. TLC and LC-MS indicated complete reaction at this point. The mixture was diluted with EtOAc (50 mL), washed with NaHCO3 (aqueous sat., 50 mL) and passed through a plug of silica gel to remove any baseline impurities. Upon concentration, the desired product (138) precipitated as a beige/pink powder that was collected by filtration under reduced pressure followed by drying under high vacuum for 16 h (1.43 g, 2.88 mmol, 58% yield). LC-MS (ESI): (exact mass: 331.01) m/e=332.1 [M+1]+ (100%), 664.9 [2M+1]+ (30%), 996.2 [3M+1]+ (10%). 1H NMR (400 MHz, DMSO-d6): δ 2.03 (s, 3H), 6.99 (d, 2H, J=7.2 Hz), 7.49 (d, 2H, J=6.8 Hz), 9.00 (s, 1H), 9.89 (s, 1H). 19F NMR (400 MHz, DMSO-d6): δ−76.55 (TFA reference), −75.89 (s, 2F).

Workup

  1. customreaction at this point
  2. washwashed with NaHCO3 (aqueous sat., 50 mL)
  3. customto remove any baseline impurities
  4. concentrationUpon concentration
  5. customthe desired product (138) precipitated as a beige/pink powder that
  6. filtrationwas collected by filtration under reduced pressure
  7. customby drying under high vacuum for 16 h (1.43 g, 2.88 mmol, 58% yield)

Sources & evidence

ORD record
ord-b9d14d5f177942fd900bbdfef1a4a0f4
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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