2-Methylbenzoic acid → HCID 25165913, compound

HRID 1178018Notes

Reaction equation

HRID 1178018 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:72]=[CH:71][CH:70]=[CH:69][C:65]=1[C:66](O)=[O:67]>CN(C=O)C.O>[CH3:63][C:64]1[CH:72]=[CH:71][CH:70]=[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 83732-Methylbenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 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 25165913HCID 25165913, compoundYield 72.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (152 mg, 0.66 mmol) was added to a stirred solution of biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (116 mg, 0.26 mmol) in DMF (1 mL). HOBT (36 mg, 0.26 mmol) and EDCI.HCl (50 mg, 0.26 mmol) were then added. After 2 minutes 2-methylbenzoic acid (30 mg, 0.22 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. The residue was washed with diethyl ether to afford 62 mg (72.9% yield) of biphenyl-4-carboxylicacid {2-[4-(2-methyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide as a pale yellow solid. LC-MS purity: 94.42%, HPLC Purity: 92.84%. 1H NMR: (DMSO) δ 8.7-8.6 (bs, 1H), 8.0 (d, 2H) 7.8 (m, 4H), 7.6-7.2 (m, 7H), 4.1-4.3 (dd, 2H), 3.8-3.4 (m, 6H), 3.2 (m, 2H), 2.2 (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
  5. washThe residue was washed with diethyl ether

Sources & evidence

ORD record
ord-da13247c09a94d9a92112ead8e42a50f
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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