Hydrochloric Acid → 4-Amino-N-{[1-(4-chlorophenyl)cyclopropyl]methyl}-3-fluorobenzamide

HRID 401824

Reaction equation

HRID 401824 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CN(C)C=O.C(N(CC)C(C)C)(C)C.[Cl:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]2([CH2:60][NH2:61])[CH2:59][CH2:58]2)=[CH:53][CH:52]=1.Cl>>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:61][CH2:60][C:57]2([C:54]3[CH:53]=[CH:52][C:51]([Cl:50])=[CH:56][CH:55]=3)[CH2:59][CH2:58]2)=[O:8])=[CH:4][C:3]=1[F:11]

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 99714-Amino-3-fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 4120166[1-(4-Chlorophenyl)cyclopropyl]methanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 577320174-Amino-N-{[1-(4-chlorophenyl)cyclopropyl]methyl}-3-fluorobenzamide

Procedure

To a mixture of 4-amino-3-fluorobenzoic acid (180.0 mg, 1.160 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU, 0.44 g, 1.2 mmol) in N,N-dimethylformamide (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.61 mL, 3.5 mmol) and C-[1-(4-chloro-phenyl)-cyclopropyl]-methylamine; hydrochloride (303.7 mg, 1.392 mmol). The reaction mixture was slowly warmed to rt. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% methanol in chloroform).

Workup

  1. customThe reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed successively with water, aqueous lithium chloride, and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on the Isco (120 g cartridge, chloroform to 12% methanol in chloroform)

Sources & evidence

ORD record
ord-84fb4d19c7494da498e16b1b3afaa9c4
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Linked notes

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