1-Hydroxybenzotriazole → 4-(5-cyano-pyridin-2-yloxy)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide

HRID 1177981Notes

Reaction equation

HRID 1177981 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[NH2:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])[CH2:23][CH2:22]1)=[O:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:61]([C:63]1[CH:64]=[CH:65][C:66]([O:69][C:70]2[CH:78]=[CH:77][C:73]([C:74](O)=[O:75])=[CH:72][CH:71]=2)=[N:67][CH:68]=1)#[N:62]>CN(C=O)C.O>[C:61]([C:63]1[CH:64]=[CH:65][C:66]([O:69][C:70]2[CH:78]=[CH:77][C:73]([C:74]([NH:17][CH2:18][C:19](=[O:20])[N:21]3[CH2:22][CH2:23][N:24]([C:27](=[O:38])[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]3)=[O:75])=[CH:72][CH:71]=2)=[N:67][CH:68]=1)#[N:62]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 521758604-((5-Cyano-2-pyridinyl)oxy)benzoic acidHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 251651264-(5-cyano-pyridin-2-yloxy)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamideYield 57.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (43 mg, 0.34 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt. (58 mg, 0.13 mmol) in DMF (1 mL). HOBT (18 mg, 0.13 mmol) and EDCI.HCl (26 mg, 0.13 mmol) were then added at room temperature. After 2 minutes, 4-(5-cyano-pyridin-2-yloxy)benzoic acid (30 mg, 0.11 mmol) was added and the resulting mixture was stirred at room temperature for 4 hrs. 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 afford 34.4 mg (57.3% yield) of 4-(5-cyano-pyridin-2-yloxy)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide. LCMS Purity: 85.6%, 1H NMR (CDCl3): δ 8.5 (ds, 1H), 8.0-7.9 (s, 3H), 7.8-7.5 (m, 4H), 7.5-7.4 (m, 1H), 7.0 (m, 2H), 4.5-3.5 (m, 8H), 3.5-3.0 (m, 3H).

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

Sources & evidence

ORD record
ord-3c009e93053d46919db43ec23d8d4816
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

Loading…