1-Hydroxybenzotriazole → HCID 178523488, compound

HRID 1093714Notes

Reaction equation

HRID 1093714 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.[F:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[CH:55][C:54]=1[NH:60][CH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C=O)C.O>[F:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[CH:55][C:54]=1[NH:60][CH:61]1[CH2:66][CH2:65][N:64]([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])[CH2:63][CH2:62]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66545655HCID 66545655, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523488HCID 178523488, compoundYield 16.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (232 mg, 1.8 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (148 mg, 0.6 mmol) in DMF (2 mL) followed by HOBt (95 mg, 0.7 mmol) and EDCI.HCl (137 mg, 0.7 mmol. After 2 minutes (2,4-difluoro-phenyl)-piperidin-4-yl-amine dihydrochloride (prepared by the method used for the synthesis of Intermediate 3) (150 mg, 0.6 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 thus collected was concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) to afford 43 mg (16.5% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,4-difluoro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 440.18, 94.52%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.1 (m, 1H), 7.8 (m, 2H), 7.4 (m, 4H), 7.0 (m, 1H), 6.9 (m, 2H), 5.0 (m, 1H), 4.4 (m, 1H), 4.2 (m, 2H), 3.5 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (m, 2H), 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. customThe organic layer thus collected
  5. concentrationwas concentrated under reduced pressure
  6. customPurification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-b3c8040ab48741fba2a1387d6376eaf6
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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