1-Hydroxybenzotriazole → HCID 178509833, compound

HRID 1093821Notes

Reaction equation

HRID 1093821 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.[NH:52]1[CH2:57][CH2:56][CH:55]([NH:58][C:59]2[CH:60]=[C:61]([CH:64]=[CH:65][CH:66]=2)[C:62]#[N:63])[CH2:54][CH2:53]1>CN(C=O)C.O>[C:62]([C:61]1[CH:60]=[C:59]([NH:58][CH:55]2[CH2:56][CH2:57][N:52]([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])[CH2:53][CH2:54]2)[CH:66]=[CH:65][CH:64]=1)#[N:63]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591754HCID 66591754, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178509833HCID 178509833, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (135 mg, 1.0 mmol) was added to a stirred of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (150 mg, 0.7 mmol) in DMF (4 mL) followed by HOBt (108 mg, 0.8 mmol) and EDCI.HCl (160 mg, 0.8 mmol). After 2 minutes of stirring 3-(piperidin-4-ylamino)-benzonitrile dihydrochloride (prepared according to Step 2 and 5 of the General Scheme) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with brine and concentrated. The residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3) to afford 91 mg (42% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-cyano-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 429.2, 92.9%, 1H NMR (300 MHz, DMSO-d6): δ 8.0 (m, 1H), 7.8 (m, 2H), 7.5 (m, 2H), 7.4 (m, 1H), 7.2 (m, 1H), 7.1 (b, 1H), 6.9 (m, 2H), 6.2 (m, 1H), 4.3 (m, 1H), 4.2 (m, 1H), 3.8 (m, 1H), 3.6 (m, 1H), 3.4 (m, 1H), 2.8 (m, 1H), 2.0 (m, 2H), 1.4 (m, 1H), 1.2 (m, 1H).

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-632ba0962a5b4862856ec5958053520b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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