1-Hydroxybenzotriazole → HCID 178523489, compound

HRID 1093715Notes

Reaction equation

HRID 1093715 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:54]=[CH:55][C:56]([C:66]([F:69])([F:68])[F:67])=[C:57]([NH:59][CH:60]2[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)[CH:58]=1>CN(C=O)C.O>[F:52][C:53]1[CH:54]=[CH:55][C:56]([C:66]([F:69])([F:67])[F:68])=[C:57]([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)[CH:58]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86634627HCID 86634627, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523489HCID 178523489, compoundYield 44.4%

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 (5-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 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. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) afforded 129 mg (44.4% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 490.18, 95.08%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.0 (bs, 1H), 7.8 (d, 2H), 7.5 (t, 4H), 7.1 (bs, 1H), 6.8 (d, 1H), 6.5 (t, 1H), 5.0 (d, 1H), 4.4 (d, 1H), 4.3 (d, 2H), 3.8 (m, 2H), 3.7 (m, 2H), 3.2 (t, 1H), 2.8 (t, 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. 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-5d473512a62645bbae3f65a3310a476e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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