1-Hydroxybenzotriazole → HCID 178523492, compound

HRID 1093727Notes

Reaction equation

HRID 1093727 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]=[CH:71][C:70]=2[Cl:75])[CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[Cl:75][C:70]1[CH:71]=[CH:72][CH:73]=[CH:74][C:69]=1[O:68][CH:65]1[CH2:64][CH2:63][N:62]([C:60](=[O:61])[CH2:59][NH:58][C:22]([C:19]2[CH:18]=[C:17]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[F:10])[NH:21][N:20]=2)=[O:24])[CH2:67][CH2:66]1

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 96744o-FluoroacetophenoneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524114HCID 178524114, compound

Product 1

HCID 178523492HCID 178523492, compoundYield 80.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (110 mg, 0.85 mmol) was added to a stirred solution of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (50 mg, 0.24 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (33 mg, 0.24 mmol) and EDCI.HCl (49 mg, 0.25 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (75 mg, 0.24 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. Recrystallisation using 25% EtOAc in hexane afforded 89 mg (80.9% Yield) of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 457, 90.38%. 1H NMR (300 MHz, DMSO-d6): 613.8 (s, 1H), 8.2 (bs, 1H), 7.9 (t, 1H), 7.1 (m, 7H), 4.61 (m, 1H), 4.4 (d, 2H), 3.7 (m, 2H), 3.3 (m, 2H), 1.9 (m, 2H), 1.5 (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. customRecrystallisation

Sources & evidence

ORD record
ord-d4409d7b630a42d59b44cb319499629b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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