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Triethylamine → 2-[5-Bromo-3-(trifluoromethyl)-1h-pyrazol-1-yl]-1-[4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]ethanone

HRID 238682
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Reaktionsgleichung

Reaktionsgleichung von HRID 238682
[Br:1][C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[N:5]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.C(Cl)(=O)C(Cl)=O.ClC1N(CC([N:30]2[CH2:35][CH2:34][CH:33]([C:36]3[S:37][CH:38]=[C:39]([C:41]4[CH2:45][CH:44]([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)[O:43][N:42]=4)[N:40]=3)[CH2:32][CH2:31]2)=O)N=C(C(F)(F)F)C=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[Br:1][C:2]1[N:6]([CH2:7][C:8]([N:30]2[CH2:35][CH2:34][CH:33]([C:36]3[S:37][CH:38]=[C:39]([C:41]4[CH2:45][CH:44]([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)[O:43][N:42]=4)[N:40]=3)[CH2:32][CH2:31]2)=[O:10])[N:5]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1
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Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 687439092-[5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-[4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]ethanoneHCID 687457105-bromo-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid2×

Produkt 1

HCID 68743847
2-[5-Bromo-3-(trifluoromethyl)-1h-pyrazol-1-yl]-1-[4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]ethanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 5-bromo-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid (i.e. the product of Example 11, Step D) (0.12 g, 0.61 mmol) in dichloromethane (5 mL) was added N,N-dimethylformamide (1 drop) followed by oxalyl chloride (0.25 mL, 2.86 mmol). The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. The residue containing crude acid chloride was taken up in dichloromethane (5 mL), and the solution was added dropwise to a mixture of 4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidine hydrochloride (i.e. the intermediate product of Example 10, Step F) (0.15 g, 0.43 mmol) and triethylamine (0.25 mL, 1.8 mmol) in dichloromethane (5 mL) at 0° C. The reaction mixture was allowed to warm to room temperature, and then stirred overnight at room temperature. The mixture was then partitioned between 1.0 N aqueous hydrochloric acid solution and dichloromethane. The organic layer was washed with water, dried (MgSO4), concentrated under reduced pressure, and purified by medium-pressure liquid chromatography using ethyl acetate in hexanes as eluant to give 90 mg of the title product, a compound of the present invention, as an amorphous solid.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue containing crude acid chloride
  3. temperatureto warm to room temperature
  4. stirringstirred overnight at room temperature
  5. customThe mixture was then partitioned between 1.0 N aqueous hydrochloric acid solution and dichloromethane
  6. washThe organic layer was washed with water
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. custompurified by medium-pressure liquid chromatography

Quellen und Nachweise

ORD-Eintrag
ord-a622a67adee940868ec3c09f507922a1
Quelldatensatz
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08642634B2

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