1-Hydroxybenzotriazole → HCID 178523487, compound

HRID 1093716Notes

Reaction equation

HRID 1093716 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]=[CH:57][C:56]([NH:59][CH:60]2[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)=[C:55]([C:66]([F:69])([F:68])[F:67])[CH:54]=1>CN(C=O)C.O>[F:52][C:53]1[CH:58]=[CH:57][C:56]([NH:59][CH:60]2[CH2:61][CH2:62][N:63]([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][CH2:65]2)=[C:55]([C:66]([F:69])([F:67])[F:68])[CH:54]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86634629HCID 86634629, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523487HCID 178523487, compoundYield 36%

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 (140 mg, 0.6 mmol) in DMF (2 mL) followed by HOBt (97 mg, 0.7 mmol) and EDCI.HCl (137 mg, 0.7 mmol). After 2 minutes (4-fluoro-2-trifluoromethyl-phenyl)-piperidin-4-yl-amine dihydrochloride (prepared according to the method used for the synthesis of Intermediate 3) (150 mg, 0.6 mmol) was added 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. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) to afford 105 mg (36% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(4-fluoro-2-trifluoromethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 490.18, 95.36%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.0 (t, 1H), 7.8 (m, 2H), 7.4 (m, 6H), 7.1 (m, 2H), 4.6 (d, 1H), 4.4 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (m, 2H), 1.5 (m, 2H), 1.4 (m, 1H).

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customPurification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-d6741ec7f66944a3ba1dfd55116e16ec
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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