1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 25166706, compound

HRID 1177911Notes

Reaction equation

HRID 1177911 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:31])([F:30])[F:29])[CH2:17][CH2:16]1)=[O:14].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[F:54][C:55]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:56]=1[C:62]1[CH:67]=[CH:66][C:65]([C:68](O)=[O:69])=[CH:64][CH:63]=1>CN(C=O)C.O>[O:14]=[C:13]([N:15]1[CH2:16][CH2:17][N:18]([C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:31])([F:29])[F:30])[CH2:19][CH2:20]1)[CH2:12][NH:11][C:68]([C:65]1[CH:66]=[CH:67][C:62]([C:56]2[CH:57]=[C:58]([F:61])[CH:59]=[CH:60][C:55]=2[F:54])=[CH:63][CH:64]=1)=[O:69]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 529837222',5'-Difluoro[1,1'-biphenyl]-4-carboxylic acidHCID 669531782-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride

Product 1

HCID 25166706HCID 25166706, compoundYield 19.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (211 mg, 0.28 mL, 1.6 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (140.5 mg, 0.399 mmol) in DMF (3 mL). HOBT (53.9 mg, 0.39 mmol) and EDCI (139.2 mg, 0.72 mmol) were then added at room temperature. After 2 minutes, 2′,5′-difluoro-biphenyl-4-carboxylic acid (85 mg, 0.36 mmol) (prepared by the method as described above) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 60% EtOAc in Hexane as eluent) to afford 38 mg (19.79% yield) of 2′,5′-difluoro-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 95.02%. 1H NMR (DMSO-d6): δ 8.7 (s, 1H), 8.0 (d, 2H), 7.9-7.65 (m, 5H), 7.6-7.46 (m, 2H), 7.44-7.25 (m, 2H), 4.3-4.1 (d, 2H), 3.6-3.4 (m, 4H), 3.26-3.04 (m, 2H).

Workup

  1. additionwas added
  2. extractionthe product was extracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto get the residue
  7. customThe obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 60% EtOAc in Hexane as eluent)

Sources & evidence

ORD record
ord-30562696040f457d90e3d03cd17ea566
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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