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

HRID 1177889Notes

Reaction equation

HRID 1177889 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([OH:25])=O)=[CH:19][CH:18]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:48][CH2:49][C:50]([N:52]1[CH2:57][CH2:56][N:55]([C:58](=[O:69])[C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[C:65]([F:68])([F:67])[F:66])[CH2:54][CH2:53]1)=[O:51]>CN(C=O)C.C(OCC)(=O)C.O>[O:51]=[C:50]([N:52]1[CH2:53][CH2:54][N:55]([C:58](=[O:69])[C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[C:65]([F:68])([F:67])[F:66])[CH2:56][CH2:57]1)[CH2:49][NH:48][C:23]([C:20]1[CH:19]=[CH:18][C:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[F:10])=[CH:22][CH:21]=1)=[O:25]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7150222'-Fluoro-biphenyl-4-carboxylic acidHCID 669531782-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride

Product 1

HCID 578556562'-Fluoro-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 37.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (71 mg, 0.09 mL, 0.55 mmol) was added to a stirred solution of 2′-fluoro-biphenyl-4-carboxylic acid (40 mg, 0.18 mmol) in DMF (1 mL). HOBT (30 mg, 0.22 mmol) and EDCI (43 mg, 0.22 mmol) were then added at room temperature. After 2 minutes 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (78 mg, 0.22 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and then extrated with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4 and concentrated under reduced pressure to afford 35 mg (36.8%) of 2′-fluoro-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 91.09%. 1H NMR (DMSO-d6): δ 8.02-7.94 (d, 2H), 7.9-7.72 (m, 2H), 7.72-7.64 (m, 3H), 7.64-7.54 (m, 2H), 7.54-7.42 (m, 1H), 7.4-7.3 (m, 2H), 4.2 (m, 2H), 3.8-3.4 (m, 2H), 3.2-3 (m, 2H).

Workup

  1. washThe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a581686016ce42cbb2a0e04d7a0ba7c6
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

Loading…