1-Hydroxybenzotriazole → HCID 44235032, compound

HRID 1093749Notes

Reaction equation

HRID 1093749 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[S:15][C:14]([C:16]2[NH:20][N:19]=[C:18]([C:21]([OH:23])=O)[CH:17]=2)=[CH:13][CH:12]=1.C(C1SC(Cl)=CC=1)(=O)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:56][CH2:57][C:58]([N:60]1[CH2:65][CH2:64][CH:63]([O:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([C:73]([F:76])([F:75])[F:74])[CH:68]=2)[CH2:62][CH2:61]1)=[O:59]>CN(C=O)C.O>[O:59]=[C:58]([N:60]1[CH2:61][CH2:62][CH:63]([O:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([C:73]([F:76])([F:74])[F:75])[CH:68]=2)[CH2:64][CH2:65]1)[CH2:57][NH:56][C:21]([C:18]1[CH:17]=[C:16]([C:14]2[S:15][C:11]([Cl:10])=[CH:12][CH:13]=2)[NH:20][N:19]=1)=[O:23]

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 805722-Acetyl-5-chlorothiopheneHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 31569925-(5-chlorothiophen-2-yl)-1H-pyrazole-3-carboxylic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 44235032HCID 44235032, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (200 mg, 1.5 mmol) was added to a stirred solution of 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid (100 mg, 0.44 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2-acetyl-5-chlorothiophene) in DMF (2 mL) followed by HOBt (63 mg, 0.46 mmol) and EDCI.HCl (90 mg, 0.46 mmol). After 5 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (140 mg, 0.44 mmol) (prepared according to Step 1 and 5 of the General Scheme) 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, dried over sodium sulfate and concentrated under reduced pressure. Purification by recrystallisation from 10% EtOAc in hexane afforded 146 mg (65.1% Yield) of 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 513, 98.3%. 1H NMR (300 MHz, DMSO-d6): δ 13.7 (s, 1H), 8.64 (m, 1H), 7.5 (t, 1H), 7.3 (m, 3H), 7.2 (m, 2H), 6.9 (m, 1H), 4.7 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 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. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby recrystallisation from 10% EtOAc in hexane

Sources & evidence

ORD record
ord-afc3eba0885b4985b1e90bbaf01a2cf6
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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