1-Hydroxybenzotriazole → HCID 178523523, compound

HRID 1093813Notes

Reaction equation

HRID 1093813 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[F:51][C:52]1[CH:53]=[C:54]([CH:62]=[C:63]([F:66])[C:64]=1[F:65])[O:55][CH:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>CN(C=O)C.O>[O:27]=[C:25]([N:59]1[CH2:60][CH2:61][CH:56]([O:55][C:54]2[CH:53]=[C:52]([F:51])[C:64]([F:65])=[C:63]([F:66])[CH:62]=2)[CH2:57][CH2:58]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:20][N:19]=1)=[O:22]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591659HCID 66591659, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523523HCID 178523523, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (135 mg, 1.0 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (69 mg, 0.3 mmol) in DMF (2.0 mL) followed by HOBt (61 mg, 0.45 mmol) and EDCI.HCl (85 mg, 0.45 mmol). After 2 minutes of stirring, 4-(3,4,5-trifluoro-phenoxy)-piperidine hydrochloride (75 mg, 0.3 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with brine and concentrated The residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3) to afford 26 mg (19% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3,4,5-trifluoro-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 459.16, 97.98%, 1H NMR (300 MHz, DMSO-d6): δ13.8 (m, 1H), 8.1 (m, 1H), 7.8 (m, 2H), 7.4 (m, 4H), 7.1 (m, 1H), 4.7 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 2.0 (m, 3H), 1.7 (m, 3H).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued at ambient temperature overnight
  4. extractionextracted with ethyl acetate
  5. washwashed with brine
  6. concentrationconcentrated The residue
  7. customwas purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-d6260b53263d44b6af609c1bc4f6cb90
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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