1-Hydroxybenzotriazole → HCID 178523528, compound

HRID 1093737Notes

Reaction equation

HRID 1093737 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][N:20]=[C:19]([C:22]([NH:24][CH2:25][C:26]([OH:28])=O)=[O:23])[CH:18]=2)=[CH:13][CH:12]=1.FC1C=CC(CC(C2C=CC=CC=2)=O)=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Cl:68][C:69]1[CH:70]=[N:71][CH:72]=[C:73]([O:75][CH:76]2[CH2:81][CH2:80][NH:79][CH2:78][CH2:77]2)[CH:74]=1>CN(C=O)C.O>[Cl:68][C:69]1[CH:74]=[C:73]([O:75][CH:76]2[CH2:81][CH2:80][N:79]([C:26](=[O:28])[CH2:25][NH:24][C:22]([C:19]3[CH:18]=[C:17]([C:14]4[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=4)[NH:21][N:20]=3)=[O:23])[CH2:78][CH2:77]2)[CH:72]=[N:71][CH:70]=1

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2363292-(4-fluorophenyl)-1-phenylethanoneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665918773-Chloro-5-(piperidin-4-yloxy)pyridine hydrochlorideHCID 178525882HCID 178525882, compound

Product 1

HCID 178523528HCID 178523528, compoundYield 53,870.801%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (200 mg, 1.6 mmol) was added to a stirred solution of {[5-(4-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid (120 mg, 0.45 mmol) (prepared by the method used for the synthesis of Intermediate 30, starting from (4′-fluorophenyl)acetophenone) in DMF (2 mL) followed by HOBt (65 mg, 0.48 mmol) and EDCI.HCl (92 mg, 0.48 mmol). After 2 minutes 3-chloro-5-(piperidin-4-yloxy)-pyridine hydrochloride (0.114 g, 0.00045 mmol) (prepared by method used for the synthesis of Intermediate 15) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure The residue was purified by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent) to afford 111 mg (55.5% Yield) of 5-(4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 458, 97.78%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.3 (m, 1H), 8.21 (m, 1H), 8.04 (m, 1H), 7.8 (m, 2H), 7.7 (m, 1H), 7.3 (m, 2H), 7.1 (s, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 2H), 3.7 (m, 1H), 3.4 (m, 1H), 3.2 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. customprepared by the method
  2. additionwas added to the reaction mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure The residue
  6. customwas purified by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent)

Sources & evidence

ORD record
ord-44dacf4297e545f8bacb2fa3ca99b4c7
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…