1-Hydroxybenzotriazole → HCID 178509670, compound

HRID 1093713Notes

Reaction equation

HRID 1093713 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:69]=[CH:68][CH:67]=[CH:66][C:63]=2[C:64]#[N:65])[CH2:57][CH2:56]1)=O>CN(C=O)C.O>[C:64]([C:63]1[CH:66]=[CH:67][CH:68]=[CH:69][C:62]=1[O:61][CH:58]1[CH2:59][CH2:60][N:55]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]2[CH:17]=[C:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:20][N:19]=2)=[O:22])[CH2:56][CH2:57]1)#[N:65]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591562HCID 66591562, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178509670HCID 178509670, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (1.3 g, 0.01 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (720 mg, 2.9 mmol) in DMF (4 mL) followed by HOBt (459 mg, 3.4 mmol) and EDCI.HCl (664 mg, 3.4 mmol). After 2 minutes of stirring, 2-[1-(2-amino-acetyl)-piperidin-4-yloxy]-benzonitrile hydrochloride (prepared by method used for the synthesis of Intermediate 15) (600 mg, 2.9 mmol) was added 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. Purification by column chromatography (using neutral alumina and 5% MeOH in CHCl3 as eluent) afforded 87 mg (6% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-cyano-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 430.18, 96.4%, 1H NMR (300 MHz, DMSO-d6): δ8.0 (m, 1H), 7.8 (m, 3H), 7.2 (m, 1H), 7.4 (m, 4H), 7.2 (m, 2H), 4.9 (m, 1H), 4.2 (bs, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued at ambient temperature overnight
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (using neutral alumina and 5% MeOH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-65276fd676d94efea73b12de1eba78a2
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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