1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2'-Methoxy-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1177912

Reaction equation

HRID 1177912 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.[CH3:54][O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=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:64]=[CH:63][C:62]([C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=2[O:55][CH3:54])=[CH:67][CH:66]=1)=[O:69]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27595482'-Methoxy-biphenyl-4-carboxylic acidHCID 669531782-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride

Product 1

HCID 251665052'-Methoxy-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 44.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (140 mg, 0.19 mL, 1.08 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (prepared by the method as described above) (119 mg, 0.38 mmol) in DMF (5 mL). HOBT (45 mg, 0.33 mmol) and EDCI (118 mg, 0.61 mmol) were then added at room temperature. After 2 minutes, 2′-Methoxy-biphenyl-4-carboxylic acid (70 mg, 0.30 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 preparative HPLC to afford 71 mg (44.1% yield) 2′-Methoxy-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 98.92%. 1H NMR (CDCl3): δ 7.94-7.84 (t, 1H), 7.8-7.72 (d, 1H), 7.7-7.56 (m, 4H), 7.5-7.44 (t, 1H), 7.4-7.3 (m, 3H), 7.1-7.0 (dd, 2H), 4.4-4.2 (m, 2H), 4.1-3.86 (m, 2H), 3.84-3.8 (s, 3H), 3.76-3.5 (m, 4H), 3.44-3.38 (t, 1H), 3.3-3.2 (bs, 2H).

Workup

  1. customprepared by the method
  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 preparative HPLC

Sources & evidence

ORD record
ord-b1ad04760e2a483c836f3cbaa64aec9c
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Linked notes

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