1-Hydroxybenzotriazole → HCID 178519541, compound

HRID 1093810Notes

Reaction equation

HRID 1093810 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.[NH:51]1[CH2:56][CH2:55][CH:54]([O:57][C:58]2[CH:65]=[CH:64][CH:63]=[CH:62][C:59]=2[CH:60]=[O:61])[CH2:53][CH2:52]1>CN(C=O)C.O>[CH:60]([C:59]1[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=1[O:57][CH:54]1[CH2:55][CH2:56][N:51]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]2[CH:17]=[C:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:20][N:19]=2)=[O:22])[CH2:52][CH2:53]1)=[O:61]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86634633HCID 86634633, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178519541HCID 178519541, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (360 mg, 2.8 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (190 mg, 0.8 mmol) in DMF (2.0 mL) followed by HOBt (160 mg, 1.2 mmol) and EDCI.HCl (230 mg, 1.2 mmol). After 2 minutes of stirring, 2-(piperidin-4-yloxy)-benzaldehyde hydrochloride (200 mg, 0.8 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 150 mg (44% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-formyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 433.18, 98.8%, 1H NMR (300 MHz, DMSO-d6): δ13.8 (m, 1H), 10.3 (s, 1H), 8.2 (m, 1H), 7.8 (m, 2H), 7.7 (m, 2H), 7.5 (m, 2H), 7.4 (m, 2H), 7.1 (m, 2H), 5.0 (m, 1H), 4.2 (m, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 2.0 (m, 2H), 1.8 (m, 2H).

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-e795af83c52f43d6b42910e84c85ed64
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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