Hydrochloric Acid → HCID 178523547, compound

HRID 1178139Notes

Reaction equation

HRID 1178139 reaction equation
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][N:53]([C:56](=[O:65])[C:57]2[CH:62]=[C:61]([Cl:63])[CH:60]=[CH:59][C:58]=2[Cl:64])[CH2:52][CH2:51]1)=[O:49].Cl>CN(C=O)C.O>[Cl:64][C:58]1[CH:59]=[CH:60][C:61]([Cl:63])=[CH:62][C:57]=1[C:56]([N:53]1[CH2:52][CH2:51][N:50]([C:48](=[O:49])[CH2:47][NH:46][C:22]([C:19]2[CH:18]=[C:17]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[OH:10])[NH:21][N:20]=2)=[O:24])[CH2:55][CH2:54]1)=[O:65]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 595595792-Amino-1-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-ethanoneHCID 178524118HCID 178524118, compound

Product 1

HCID 178523547HCID 178523547, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (170.4 mg, 0.23 mL, 1.3 mmol) was added drop wise to 5-(2-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid (prepared by the method as described above) (60 mg, 0.29 mmol) in DMF (2 mL). EDCI (140.4 mg, 0.73 mmol) and HOBT (43.6 mg, 0.32 mmol) were then added. After 2 minutes, 2-Amino-1-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-ethanone in its HCl salt form (113.9 mg, 0.32 mmol) was added. 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 purified by column chromatography (using silica gel of 60-120 mesh and 10% MeOH in CHCl3 as eluent) to afford 28 mg (20% yield) of 5-(2-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 97.07%. 1H NMR (DMSO-d6): δ 13.3 (s, 1H), 10.3 (s, 1H), 8.0 (t, 1H), 7.8-7.4 (m, 4H), 7.28-7.1 (t, 1H), 7.1-7.05 (s, 1H), 7.02-6.8 (m, 2H), 4.3-4.1 (d, 2H), 3.8-3.6 (m, 4H), 3.55-3.42 (s, 2H), 3.3-3.1 (m, 3H).

Workup

  1. customprepared by the method
  2. extractionthe product was extracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto get the residue
  7. custompurified by column chromatography (using silica gel of 60-120 mesh and 10% MeOH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-8c4df10ae33343d3b0653a4d49d6d6a5
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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