1-Hydroxybenzotriazole → HCID 178523526, compound

HRID 1093721Notes

Reaction equation

HRID 1093721 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.[Cl:51][C:52]1[CH:53]=[N:54][CH:55]=[C:56]([O:58][CH:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[CH:57]=1>CN(C=O)C.O>[Cl:51][C:52]1[CH:57]=[C:56]([O:58][CH:59]2[CH2:64][CH2:63][N:62]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]3[CH:17]=[C:16]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:20][N:19]=3)=[O:22])[CH2:61][CH2:60]2)[CH:55]=[N:54][CH:53]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665918773-Chloro-5-(piperidin-4-yloxy)pyridine hydrochlorideHCID 178525878HCID 178525878, compound

Product 1

HCID 178523526HCID 178523526, compoundYield 12.71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (387 mg, 3.0 mmol) was added a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (247 mg, 1.0 mmol) in DMF (2 mL) followed by HOBt (162 mg, 1.2 mmol) and EDCI.HCl (229 mg, 1.2 mmol). After 2 minutes 3-chloro-5-(piperidin-4-yloxy)-pyridine hydrochloride (prepared according to the 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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) to afford 56 mg (12.71% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 440.14, 95.7%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.2 (m, 2H), 8.0 (m, 1H), 7.8 (m, 3H), 7.4 (m, 4H), 7.1 (m, 1H), 4.8 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.8 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. additionwas added to the reaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customPurification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-b06e5f11dc8e48ef8839514c34195425
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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