3-Acetylpyridine → HCID 178523557, compound

HRID 1093854Notes

Reaction equation

HRID 1093854 reaction equation
CCN(C(C)C)C(C)C.[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]([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:11]=1.C(C1C=NC=CC=1)(=O)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[F:59][C:60]([F:73])([F:72])[C:61]1[CH:62]=[C:63]([CH:69]=[CH:70][CH:71]=1)[O:64][CH:65]1[CH2:68][NH:67][CH2:66]1>CN(C=O)C.O>[O:27]=[C:25]([N:67]1[CH2:68][CH:65]([O:64][C:63]2[CH:69]=[CH:70][CH:71]=[C:61]([C:60]([F:59])([F:73])[F:72])[CH:62]=2)[CH2:66]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:12]2[CH:11]=[N:10][CH:15]=[CH:14][CH:13]=2)[NH:20][N:19]=1)=[O:22]

Participants

9

Reactant 6

HCID 95893-AcetylpyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 510516403-[3-(Trifluoromethyl)phenoxy]-azetidine hydrochlorideHCID 178525883HCID 178525883, compound

Product 1

HCID 178523557HCID 178523557, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (158.2 mg, 1.22 mmol) was added to a stirred solution of [(5-pyridin-3-yl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 30, starting from 3-acetylpyridine) (76 mg, 0.30 mmol) in DMF (2 mL) followed by HOBt (43.4 mg, 0.32 mmol) and EDCI (61.6 mg, 0.32 mmol). After 2 minutes of stirring, 3-(3-trifluoromethyl-phenoxy)-azetidine hydrochloride (77.5 mg, 0.3 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure The residue obtained purified by column chromatography (using silica gel 60- and 100% ethyl acetate as eluent) to afford 43 mg (32% Yield) of 5-pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[3-(3-trifluoromethyl-phenoxy)-azetidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 446.14, 93.76%. 1H NMR (300 MHz, DMSO-d6): δ 9.44 (s, 1H), 9.2 (d, 1H), 8.72 (m, 2H), 8.38 (m, 1H), 7.64 (m, 1H), 7.52 (t, 1H), 7.35 (d, 1H), 7.16 (m, 2H), 5.2 (m, 1H), 4.7 (m, 1H), 4.3 (m, 1H), 4.2 (m, 1H), 3.95 (d, 2H), 3.8 (m, 1H).

Workup

  1. customprepared by the method
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure The residue
  6. customobtained
  7. custompurified by column chromatography (using silica gel 60- and 100% ethyl acetate as eluent)

Sources & evidence

ORD record
ord-e8f3b4bb6d7241238c11df2e9e87f3c6
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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