1-Hydroxybenzotriazole → HCID 178497862, compound

HRID 1093725Notes

Reaction equation

HRID 1093725 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.[CH3:51][O:52][C:53](=[O:68])[C:54]1[CH:59]=[CH:58][C:57]([CH3:60])=[C:56]([O:61][CH:62]2[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]2)[CH:55]=1>CN(C=O)C.O>[CH3:51][O:52][C:53](=[O:68])[C:54]1[CH:59]=[CH:58][C:57]([CH3:60])=[C:56]([O:61][CH:62]2[CH2:67][CH2:66][N:65]([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])[CH2:64][CH2:63]2)[CH:55]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66592375HCID 66592375, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178497862HCID 178497862, compoundYield 68.55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (423 mg, 2.4 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (200 mg, 0.81 mmol) in DMF (3 mL) followed by HOBt (130 mg, 0.93 mmol) and EDCI.HCl (187 mg, 0.93 mmol). After 2 minutes 4-methyl-3-(piperidin-4-yloxy)-benzoic acid methyl ester hydrochloride (prepared according to the method used for the synthesis of Intermediate 15) (280 mg, 0.97 mmol) 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 to afford 266 mg (68.55% Yield) of 4-methyl-3-(1-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid methyl ester. LC/MS [M+H]+: 477.21, 96.63%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.1-8.0 (m, 1H), 7.8 (d, 2H), 7.54-7.28 (m, 6H), 7.1 (bs, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8 (s, 3H), 3.8-3.6 (m, 2H), 3.6-3.4 (m, 2H), 2.2 (s, 3H), 2.1-1.8 (m, 2H), 1.8-1.5 (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

Sources & evidence

ORD record
ord-944086e5cf5845089adaa2e3cd39d85b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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