1-Hydroxybenzotriazole → HCID 178523524, compound

HRID 1093720Notes

Reaction equation

HRID 1093720 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.NCC([N:55]1[CH2:60][CH2:59][CH:58]([O:61][C:62]2[CH:67]=[CH:66][N:65]=[CH:64][CH:63]=2)[CH2:57][CH2:56]1)=O>CN(C=O)C.O>[O:27]=[C:25]([N:65]1[CH2:66][CH2:67][CH:62]([O:61][C:58]2[CH:59]=[CH:60][N:55]=[CH:56][CH:57]=2)[CH2:63][CH2:64]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:20][N:19]=1)=[O:22]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591711HCID 66591711, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523524HCID 178523524, compoundYield 34.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (540 mg, 4.2 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (344 mg, 1.4 mmol) in DMF (3 mL) followed by HOBt (229 mg, 1.7 mmol) and EDCI.HCl (321 mg, 1.7 mmol). After 2 minutes 2-amino-1-[4-(pyridin-4-yloxy)-piperidin-1-yl]-ethanone hydrochloride (250 mg, 1.4 mmol) (prepared according to Step 1 and 5 of the General Scheme) 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 198 mg (% 34.9 Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(pyridin-4-yloxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 406.18, 95.8%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (m, 1H), 8.4 (m, 2H), 8.1 (m, 1H), 7.8 (m, 2H), 7.1 (m, 1H), 7.0 (s, 2H), 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), 1.7 (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-2122900a022848199013ab6c906d0684
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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