Triethylamine → trans 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid {1-[2-(5-chloro-thiophen-2-yl)-cyclopropyl]-ethyl}-methoxy-amide

HRID 1807391Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1807391
[Cl:1][C:2]1[S:6][C:5]([C@@H:7]2[CH2:9][C@H:8]2[CH:10]([NH:12][O:13][CH3:14])[CH3:11])=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:22][CH:23]([F:33])[C:24]1[C:28]([C:29](Cl)=[O:30])=[CH:27][N:26]([CH3:32])[N:25]=1>ClCCl.O>[Cl:1][C:2]1[S:6][C:5]([C@@H:7]2[CH2:9][C@H:8]2[CH:10]([N:12]([O:13][CH3:14])[C:29]([C:28]2[C:24]([CH:23]([F:33])[F:22])=[N:25][N:26]([CH3:32])[CH:27]=2)=[O:30])[CH3:11])=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 86669066trans N-{1-[2-(5-chloro-thiophen-2-yl)-cyclopropyl]-ethyl}-O-methyl-hydroxylamine

Produkt 1

HCID 131730170trans 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid {1-[2-(5-chloro-thiophen-2-yl)-cyclopropyl]-ethyl}-methoxy-amideAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred solution of trans N-{1-[2-(5-Chloro-thiophen-2-yl)-cyclopropyl]-ethyl}-O-methyl-hydroxylamine (0.19 g; 0.83 mmol) prepared as described in example P18 and triethylamine (0.16 ml; 1.08 mmol) in dichloromethane (5.0 ml) at ambient temperature was added dropwise 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.16 g; 0.83 mmol). The reaction mixture was stirred for 16 hours at ambient temperature then poured in water (3 ml) and extracted with dichloromethane (3×1 ml). Combined organic layers were washed with water (1 ml) and dried over anhydrous sodium sulphate. The solvent was removed in vacuo and the residue was purified by flash chromatography over silica gel (elution gradient: cyclohexane/ethyl acetate 99:1 to 30:70) to afford 0.31 g (97% of theory) of trans 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid {1-[2-(5-chloro-thiophen-2-yl)-cyclopropyl]-ethyl}-methoxy-amide as a resin.

Aufarbeitung

  1. extractionextracted with dichloromethane (3×1 ml)
  2. washCombined organic layers were washed with water (1 ml)
  3. dry with materialdried over anhydrous sodium sulphate
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by flash chromatography over silica gel (elution gradient: cyclohexane/ethyl acetate 99:1 to 30:70)

Quellen und Nachweise

ORD-Eintrag
ord-e7586c5dc9a64b34b40f7ec67bb672f8
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08357635B2

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