1-Hydroxybenzotriazole → HCID 25165912, compound

HRID 1178019Notes

Reaction equation

HRID 1178019 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.[Br:63][C:64]1[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][C:65]=1[C:66](O)=[O:67]>CN(C=O)C.O>[Br:63][C:64]1[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][C:65]=1[C:66]([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:67]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 899062-Bromo-5-methoxybenzoic 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 25165912HCID 25165912, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (66 mg, 0.51 mmol) was added to a stirred solution of biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (90 mg, 0.21 mmol) in DMF (2 mL). HOBT (28 mg, 0.21 mmol) and EDCI.HCl (40 mg, 0.21 mmol) were then added. After 2 minutes 2-bromo-5-methoxy benzoic acid (40 mg, 0.17 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 crude product, which was purified by column chromatography (using silica gel of 160-120 mesh and 2.5% MeOH in chloroform as eluent) to afford 31 mg (34% yield) of biphenyl-4-carboxylic acid {2-[4-(2-bromo-5-methoxy-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide as a white solid. LC-MS purity: 98.31%, HPLC Purity: 97.73%. 1H NMR: (DMSO) δ 8.7-8.6 (b s, 1H), 8.0 (m, 2H), 7.8 (m, 4H), 7.6-7.4 (m, 4H), 7.0 (m, 2H), 4.2 (m, 2H), 3.8 (s, 3H), 3.4-3.7 (m, 6H), 3.2-3.1 (m, 2H).

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
  5. customto afford crude product, which
  6. customwas purified by column chromatography (using silica gel of 160-120 mesh and 2.5% MeOH in chloroform as eluent)

Sources & evidence

ORD record
ord-cd4b376c530a4176a0183548c47249a4
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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