1-Hydroxybenzotriazole → HCID 56296296, compound

HRID 1178131Notes

Reaction equation

HRID 1178131 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:20]1([C:26]2[O:30][N:29]=[C:28]([C:31]([OH:33])=O)[CH:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.Cl.[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][N:53]([C:56](=[O:67])[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:65])[F:64])[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[O:49]=[C:48]([N:50]1[CH2:51][CH2:52][N:53]([C:56](=[O:67])[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:65])[F:64])[CH2:54][CH2:55]1)[CH2:47][NH:46][C:31]([C:28]1[CH:27]=[C:26]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[O:30][N:29]=1)=[O:33]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1519165-Phenyl-3-isoxazolecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 595596292-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone

Product 1

HCID 56296296HCID 56296296, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (44.6 mg, 0.33 mmol) and DIPEA (136.7 mg, 1.06 mmol) were added to a stirred solution of 5-phenyl-isoxazole-3-carboxylic acid (50 mg, 0.27 mmol) in DMF (1.0 mL). The reaction mixture was then cooled to 10° C. and EDCI.HCl (63.3 mg, 0.33 mmol) was added, followed by the addition 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone (as TFA salt) (113.5 mg, 0.27 mmol). Then resulting mixture was stirred at room temperature overnight. The reaction mixture was then diluted with water and the product extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. The crude product thus obtained was purified by column chromatography using neutral alumina as stationary phase and 100% ethyl acetate as the eluent to afford 5-phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide as a solid in 20.3% yield. LC-MS purity: 98.075%, 1H NMR (DMSO-D6): δ 8.6 (s, 1H), 7.9 (m, 2H), 7.7 (m, 2H), 7.65 (m, 1H), 7.5 (m, 3H), 7.4 (s, 1H), 4.1 (m, 2H), 3.6 (m, 4H), 3.4 (m, 2H), 3.1 (m, 2H).

Workup

  1. customThen resulting mixture
  2. extractionthe product extracted with ethyl acetate
  3. washThe organic layer was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product thus obtained
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-a3a7bf53b8d947a8b98b47cbe80c471d
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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