1-Hydroxybenzotriazole → HCID 178485311, compound

HRID 1093818Notes

Reaction equation

HRID 1093818 reaction equation
C[CH2:2][N:3](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]([N:27]3[CH2:32][CH2:31][CH:30]([O:33][C:34]4[CH:42]=[CH:41][CH:40]=[CH:39][C:35]=4[C:36]([OH:38])=O)[CH2:29][CH2:28]3)=[O:26])=[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.CN>CN(C=O)C.O>[CH3:2][NH:3][C:36]([C:35]1[CH:39]=[CH:40][CH:41]=[CH:42][C:34]=1[O:33][CH:30]1[CH2:31][CH2:32][N:27]([C:25](=[O:26])[CH2:24][NH:23][C:21]([C:18]2[CH:17]=[C:16]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[NH:20][N:19]=2)=[O:22])[CH2:28][CH2:29]1)=[O:38]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 178523500HCID 178523500, compound

Product 1

HCID 178485311HCID 178485311, compoundYield 31.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (72 mg, 0.56 mmol) was added to a stirred solution of 2-(1-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid (75 mg, 0.16 mmol) in DMF (2 mL) followed by HOBt (33 mg, 0.24 mmol) and EDCI.HCl (46 mg, 0.24 mmol). After 2 minutes of stirring, methyl amine hydrochloride (11 mg, 0.16 mmol) 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) afford 23 mg (31.5% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-methylcarbamoyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 462.2, 96.9%. 1H NMR (300 MHz, DMSO-d6): δ 8.1 (m, 1H), 8.0 (m, 1H), 7.8 (m, 2H), 7.6 (m, 1H), 7.4 (m, 4H), 7.2 (m, 1H), 7.1 (b, 1H), 7.0 (m, 1H), 4.8 (b, 1H), 4.2 (m, 2H), 3.6 (m, 3H), 2.8 (d, 3H), 2.0 (m, 2H), 1.8 (m, 2H).

Workup

  1. stirringstirring
  2. waitwas continued at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. concentrationconcentrated The residue
  6. customwas purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-553849e2236a455eb7a850534a2ba3c1
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…