Hydrochloric Acid → (2r)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(morpholinocarboxymethyl)-1h-pyrazol-4-yl]methyl]piperazine hydrochloride

HRID 584199Notes

Reaction equation

HRID 584199 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[O:7].O.ON1C2C=CC=CC=2N=N1.[ClH:53].C(N=C=NCCCN(C)C)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1.Cl.C(OC(C)C)(C)C>O1CCCC1.C(OCC)(=O)C>[ClH:53].[F:39][C:36]([F:38])([F:37])[C:34]1[CH:33]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:40])[F:41])[CH:35]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH:20]([N:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]3)[C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[O:7]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 54368795(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine

Product 1

HCID 87947237(2r)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(morpholinocarboxymethyl)-1h-pyrazol-4-yl]methyl]piperazine hydrochloride

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (120 mg) in tetrahydrofuran (1 ml) were added 1-hydroxybenzotriazole hydrate (176 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg) and morpholine (0.11 ml) at room temperature, and the mixture was stirred at room temperature overnight. The mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on a silica gel using a mixture of methanol and ethyl acetate (1:9) as eluent to give a crude oil (76.7 mg). The oil was dissolved in ethyl acetate (0.7 ml) and added 4N hydrogen chloride in ethyl acetate (0.15 ml) at room temperature. After the addition of isopropyl ether, the resulting precipitate was filtered off and dried under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(morpholinocarboxymethyl)-1H-pyrazol-4-yl]methyl]piperazine hydrochloride (40 mg) as a powder.

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on a silica gel using
  7. additiona mixture of methanol and ethyl acetate (1:9) as eluent
  8. customto give a crude oil (76.7 mg)
  9. filtrationthe resulting precipitate was filtered off
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-d7a06d870a934fe9931fd596bee8102e
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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