3-Chloro-4-fluoroaniline → N-[4-(2,2-Difluoroethyl)oxy-3-(4-fluoro-3-chloro-phenyl)aminocarbonyl-phenyl]-2-chloro-5-(tert-butylcarbonylamino)methyl-benzamide

HRID 1846093Notes

Reaction equation

HRID 1846093 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][CH:26]([F:56])[CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36](=[O:52])[C:37]2[CH:42]=[C:41]([CH2:43][NH:44][C:45]([C:47]([CH3:50])([CH3:49])[CH3:48])=[O:46])[CH:40]=[CH:39][C:38]=2[Cl:51])=[CH:31][C:30]=1[C:53]([OH:55])=O.[Cl:57][C:58]1[CH:59]=[C:60]([CH:62]=[CH:63][C:64]=1[F:65])[NH2:61]>C1COCC1>[F:25][CH:26]([F:56])[CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36](=[O:52])[C:37]2[CH:42]=[C:41]([CH2:43][NH:44][C:45]([C:47]([CH3:50])([CH3:49])[CH3:48])=[O:46])[CH:40]=[CH:39][C:38]=2[Cl:51])=[CH:31][C:30]=1[C:53]([NH:61][C:60]1[CH:62]=[CH:63][C:64]([F:65])=[C:58]([Cl:57])[CH:59]=1)=[O:55]

Participants

5

Reactant 3

HCID 97083-Chloro-4-fluoroanilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86658668N-[4-(2,2-difluoroethyl)oxy-3-hydroxycarbonyl-phenyl]-2-chloro-5-(tert-butylcarbonylamino)methyl-benzamide

Product 1

HCID 52919087N-[4-(2,2-Difluoroethyl)oxy-3-(4-fluoro-3-chloro-phenyl)aminocarbonyl-phenyl]-2-chloro-5-(tert-butylcarbonylamino)methyl-benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HATU (43 mg, 0.11 mmol) was added to N-[4-(2,2-difluoroethyl)oxy-3-hydroxycarbonyl-phenyl]-2-chloro-5-(tert-butylcarbonylamino)methyl-benzamide (50.0 mg, 0.107 mmol) in 5.0 mL THF, followed by 52 μL TEA and the mixture was stirred for 15 min. Then 3-chloro-4-fluoroaniline (15.5 mg, 0.107 mmol) was added and it was stirred for 4 h at rt. The crude mixture was concentrated, EtOAc was added and the organic phase was washed with satd. aq. NaHCO3-solution, water and satd. NaCl-solution. The organic phase was dried with Na2SO4 and concentrated i. vac. to give the title compound.

Workup

  1. stirringit was stirred for 4 h at rt
  2. concentrationThe crude mixture was concentrated
  3. additionEtOAc was added
  4. washthe organic phase was washed with satd
  5. dry with materialThe organic phase was dried with Na2SO4
  6. concentrationconcentrated i

Sources & evidence

ORD record
ord-5cb76b8ba72e4164b1804edd31422b03
Source dataset
uspto-grants-2015_02
Patent number
US08951999B2

Reaction notes

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