1-Hydroxybenzotriazole → HCID 178488294, compound

HRID 1093711Notes

Reaction equation

HRID 1093711 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]([NH:61][C:62]2[CH:67]=[C:66]([Br:68])[CH:65]=[CH:64][C:63]=2[O:69][CH3:70])[CH2:57][CH2:56]1)=O>CN(C=O)C.O>[Br:68][C:66]1[CH:65]=[CH:64][C:63]([O:69][CH3:70])=[C:62]([NH:61][CH:58]2[CH2:57][CH2:56][N:55]([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])[CH2:60][CH2:59]2)[CH:67]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591921HCID 66591921, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178488294HCID 178488294, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (45 mg, 0.35 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (26 mg, 0.1 mmol) in DMF (1 mL) followed by HOBt (20 mg, 0.15 mmol) and EDCI.HCl (28 mg, 0.15 mmol). After 2 minutes of stirring, 2-amino-1-[4-(5-bromo-2-methoxy-phenylamino)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 2 and 5 of the General Scheme) (0.03 g, 0.0001 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) to afford 60 mg (35% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-bromo-2-methoxy-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 512.4, 91%, 1H NMR (300 MHz, DMSO-d6): δ10.2 (m, 1H), 7.9 (m, 1H), 7.7 (m, 7H), 7.4 (m, 2H), 7.2 (m, 1H), 3.6 (m, 5H), 2.0 (m, 2H), 1.8 (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 Purification by column chromatography (using neutral alumina and 5% MeOH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-761ed541f9d44681aea761b1d911d5ae
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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