1-Hydroxybenzotriazole → Biphenyl-4-carboxylicacid {2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1178017Notes

Reaction equation

HRID 1178017 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[O:17]=[C:18]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)[CH2:19][NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)=[O:22].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:63][C:64]1[CH:68]=[CH:67][S:66][C:65]=1[C:69](O)=[O:70]>CN(C=O)C.O>[CH3:63][C:64]1[CH:68]=[CH:67][S:66][C:65]=1[C:69]([N:38]1[CH2:39][CH2:40][N:35]([C:18](=[O:17])[CH2:19][NH:20][C:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:27][CH:28]=2)=[O:22])[CH2:36][CH2:37]1)=[O:70]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 902693-Methyl-2-thenoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131728551biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt

Product 1

HCID 66953459Biphenyl-4-carboxylicacid {2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 72.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (110.8 mg, 0.147 mL, 0.85 mmol) was added to a stirred solution of biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (100 mg, 0.22 mmol) in DMF (3 mL). HOBT (28.3 mg, 0.2 mmol) and EDCI.HCl (91.25 mg, 0.47 mmol) were then added. After 2 minutes 3-methyl-thiophene-2-carboxylic acid (27 mg, 0.19 mmol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water. The product was extracted with ethyl acetate and the ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford 62 mg (72.9% yield) of biphenyl-4-carboxylicacid {2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 90.22%, HPLC Purity: 92.38%, 1H NMR: (CDCl3) δ 7.9 (d, 2H), 7.75-7.6 (m, 4H), 7.5 (m, 2H), 7.4 (m, 1H), 7.3-7.4 (m, 2H), 6.9 (d, 1H), 4.3 (d, 2H), 3.7 (m, 6H), 3.5 (m, 2H), 2.4 (s, 3H).

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. washthe ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f366abfac90a45b8a7be27b6ae9c0e42
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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