1-Hydroxybenzotriazole → HCID 178523506, compound

HRID 1093728Notes

Reaction equation

HRID 1093728 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=1.FC1C=CC=CC=1C(=O)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:58][CH2:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:74]=[CH:73][CH:72]=[C:71]([C:75]([F:78])([F:77])[F:76])[CH:70]=2)[CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[O:61]=[C:60]([N:62]1[CH2:63][CH2:64][CH:65]([O:68][C:69]2[CH:74]=[CH:73][CH:72]=[C:71]([C:75]([F:78])([F:76])[F:77])[CH:70]=2)[CH2:66][CH2:67]1)[CH2:59][NH:58][C:22]([C:19]1[CH:18]=[C:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[F:10])[NH:21][N:20]=1)=[O:24]

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 96744o-FluoroacetophenoneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524114HCID 178524114, compound

Product 1

HCID 178523506HCID 178523506, compoundYield 31.67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (160 mg, 1.3 mmol) was added to a stirred solution of 5-(2-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (77 mg, 0.37 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (52 mg, 0.39 mmol) and EDCI.HCl (74 mg, 0.39 mmol). After 2 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (125 mg, 0.37 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 the residue. Washing with ethyl acetate afforded 57 mg (31.67% Yield) of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 491, 93.63%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (d, 1H), 8.7 (m, 1H), 7.8 (m, 1H), 7.2 (m, 6H), 6.9 (m, 2H), 4.8 (m, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.4 (m, 2H), 1.9 (m, 2H), 1.6 (m, 2H).

Workup

  1. customprepared by the method
  2. additionwas added to the reaction mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customto afford the residue
  7. washWashing with ethyl acetate

Sources & evidence

ORD record
ord-7baae041c36d4876ad1092dca398dd77
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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