1-Hydroxybenzotriazole → HCID 178523516, compound

HRID 1093724Notes

Reaction equation

HRID 1093724 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:57]=[CH:56][CH:55]=[C:54]([O:58][CH:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[N:53]=1>CN(C=O)C.O>[Cl:51][C:52]1[N:53]=[C:54]([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]=[CH:56][CH:57]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13564003HCID 13564003, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523516HCID 178523516, compoundYield 18.27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (271 mg, 2.1 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (162 mg, 0.7 mmol) in DMF (2 mL) followed by HOBt (94 mg, 0.7 mmol) and EDCI.HCl (134 mg, 0.7 mmol). After 2 minutes 2-chloro-6-(piperidin-4-yloxy)-pyridine hydrochloride (prepared according to the method used for the synthesis of Intermediate 15) (140 mg, 0.7 mmol) 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) afforded 53 mg (18.27% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(6-chloro-pyridin-2-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 440.14, 90%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.2 (b, 1H), 7.8 (m, 3H), 7.4 (m, 3H), 7.1 (m, 1H), 6.8 (m, 1H), 5.2 (m, 1H), 4.2 (m, 2H), 3.8 (m, 1H), 3.7 (m, 1H), 3.5 (m, 2H), 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-6d84f22c6cef4c238c4c71452e867279
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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