Hydrochloric Acid → HCID 178523533, compound

HRID 1093723Notes

Reaction equation

HRID 1093723 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.[F:51][C:52]([F:69])([F:68])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[S:59]([CH:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)(=[O:61])=[O:60].C(OC(N1CCC(SC2C=CC=CC=2C(F)(F)F)CC1)=O)(C)(C)C.OO.Cl>CN(C=O)C.O>[O:27]=[C:25]([N:65]1[CH2:64][CH2:63][CH:62]([S:59]([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2[C:52]([F:68])([F:51])[F:69])(=[O:61])=[O:60])[CH2:67][CH2:66]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:20][N:19]=1)=[O:22]

Participants

11

Reactant 8

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591335HCID 66591335, compoundHCID 66591727HCID 66591727, compoundHCID 178525878HCID 178525878, compound

Product 1

HCID 178523533HCID 178523533, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (88 mg, 0.68 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (36 mg, 0.15 mmol) in DMF (1 mL) followed by HOBt (20 mg, 0.15 mmol) and EDCI.HCl (39 mg, 0.2 mmol). After 2 minutes 4-(2-trifluoromethyl-benzenesulfonyl)-piperidine hydrochloride (250 mg, 1.0 mmol) (prepared from 4-(2-trifluoromethyl-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester by means of oxidation with hydrogen peroxide and subsequent hydrolysis of the N-protection group with hydrochloric acid) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, the precipitate was collected. The solid obtained was purified by column chromatography (using 60-120 silica gel and 5% MeoH in DCM as eluent) to afford 21 mg (29.6% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzenesulfonyl)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 521.14, 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.2 (m, 5H), 7.7 (d, 2H), 7.5-7.3 (m, 3H), 7.1 (s, 1H), 4.5 (d, 1H), 4.2-4.0 (m, 2H), 4.0 (d, 1H), 3.7-3.5 (t, 1H), 3.1 (t, 1H), 2.7 (m, 1H), 1.9-1.7 (m, 2H), 1.7 (m, 1H), 1.5 (m, 1H).

Workup

  1. additionwas added to the reaction mixture
  2. customthe precipitate was collected
  3. customThe solid obtained
  4. customwas purified by column chromatography (using 60-120 silica gel and 5% MeoH in DCM as eluent)

Sources & evidence

ORD record
ord-52c58d5963c442868b5f19e00f220a17
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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