1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-benzyloxy-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-nicotinamide

HRID 1177904Notes

Reaction equation

HRID 1177904 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.[CH2:54]([O:61][C:62]1[CH:70]=[CH:69][C:65]([C:66](O)=[O:67])=[CH:64][N:63]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>CN(C=O)C.O>[CH2:54]([O:61][C:62]1[CH:70]=[CH:69][C:65]([C:66]([NH:11][CH2:12][C:13](=[O:14])[N:15]2[CH2:16][CH2:17][N:18]([C:21](=[O:32])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]([F:31])([F:29])[F:30])[CH2:19][CH2:20]2)=[O:67])=[CH:64][N:63]=1)[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2772386-(Benzyloxy)pyridine-3-carboxylic acidHCID 669531782-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride

Product 1

HCID 251669256-benzyloxy-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-nicotinamideYield 45.33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (253 mg, 0.34 mL, 1.9 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (184 mg, 0.52 mmol) in DMF (4 mL). HOBT (64.8 mg, 0.479 mmol) and EDCI (167 mg, 0.87 mmol) were then added at room temperature. After 2 minutes, 6-benzyloxy-nicotinic acid (100 mg, 0.43 mmol) 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 70% EtOAc in Hexane as eluent) to afford 102 mg (45.33% yield) 6-benzyloxy-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-nicotinamide. LCMS Purity: 98.91%. 1H NMR (DMSO-d6): δ 8.7 (d, 2H), 8.2-8.1 (d, 1H), 7.9-7.64 (m, 5H), 7.62-7.5 (m, 1H), 7.5-7.3 (m, 3H), 7.0-6.9 (d, 1H), 5.4 (s, 2H), 4.24-4.06 (d, 2H), 3.8-3.56 (m, 4H), 3.54-3.4 (m, 2H), 3.2-3.02 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto get the residue
  6. customThe obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 70% EtOAc in Hexane as eluent)

Sources & evidence

ORD record
ord-9eb89abd32ff46a59f669d04a42dd362
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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