1-Hydroxybenzotriazole → HCID 178523518, compound

HRID 1093736Notes

Reaction equation

HRID 1093736 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.[ClH:66].Cl.Cl[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:66][C:72]1[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:74][CH:69]=[CH:70][N:71]=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 178523518HCID 178523518, compoundYield 58.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (226 mg, 1.75 mmol) was added to a stirred solution of {[5-(4-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid (130 mg, 0.5 mmol) (prepared by the method used for the synthesis of Intermediate 30, starting from (4-fluorophenyl)acetophenone) in DMF (2 mL) followed by HOBt (71 mg, 0.52 mmol) and EDCI.HCl (100 mg, 0.52 mmol). After 2 minutes 3-chloro-5-(piperidin-4-yloxy)-pyridine hydrochloride (125 mg, 0.5 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 40% ethyl acetate in hexane as eluent) to afford 134 mg (58.5% Yield) of 5-(4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 458, 93.27%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.0 (m, 2H), 7.8 (m, 2H), 7.7 (d, 1H), 7.4 (m, 1H), 7.25 (m, 2H), 7.1 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 1.9 (m, 2H), 1.7 (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 40% ethyl acetate in hexane as eluent)

Sources & evidence

ORD record
ord-88deb227746b4bbf84b0d24ac0e4c8c8
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…