1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Biphenyl-4-carboxylic acid {2-[4-(6-chloro-pyridine-3-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1177990Notes

Reaction equation

HRID 1177990 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[N:16]=[CH:15][C:14]([C:17]([OH:19])=O)=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[O:41]=[C:42]([N:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1)[CH2:43][NH:44][C:45]([C:47]1[CH:52]=[CH:51][C:50]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[CH:49][CH:48]=1)=[O:46]>CN(C=O)C.O>[Cl:10][C:11]1[N:16]=[CH:15][C:14]([C:17]([N:62]2[CH2:61][CH2:60][N:59]([C:42](=[O:41])[CH2:43][NH:44][C:45]([C:47]3[CH:52]=[CH:51][C:50]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)=[CH:49][CH:48]=3)=[O:46])[CH2:64][CH2:63]2)=[O:19])=[CH:13][CH:12]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 792226-Chloronicotinic acidHCID 81531DiisopropylethylamineHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Product 1

HCID 59559640Biphenyl-4-carboxylic acid {2-[4-(6-chloro-pyridine-3-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 40.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (179.7 mg, 0.24 mL, 1.39 mmol) was added to a stirred solution of 6-chloro-pyridine-3-carboxylic acid (48.6 mg, 0.37 mmol) in DMF (3 mL). HOBT (45.9 mg, 0.34 mmol) and EDCI (148.1 mg, 0.77 mmol) were then added at room temperature. After 2 minutes, Biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide (120 mg, 0.37 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 90% EtOAc in Hexane as eluent) to afford 58 mg (40.8% yield) of biphenyl-4-carboxylic acid {2-[4-(6-chloro-pyridine-3-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 95.92, 1H NMR (DMSO-d6): δ 8.7-8.6 (t, 1H), 8.5 (d, 1H), 8.0-7.9 (m, 3H), 7.84-7.7 (q, 4H), 7.68-7.6 (d, 1H), 7.54-7.46 (t, 2H), 7.46-7.36 (m, 1H), 4.2 (bs, 2H), 3.8-3.4 (m, 8H).

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 90% EtOAc in Hexane as eluent)

Sources & evidence

ORD record
ord-050b7f1489be4d698deb5d084b77bdd3
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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