Triethylamine → N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide

HRID 77693Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 77693
[F:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[C:9](Cl)=[O:10].[C:12]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][NH:21][CH:22]2[CH2:24][CH2:23]2)=[CH:14][CH:13]=1.C(N(CC)CC)C.CCCCCCC.C(OCC)(=O)C>O1CCCC1>[C:12]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]([CH:22]2[CH2:24][CH2:23]2)[C:9]([C:3]2[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=2[F:1])=[O:10])=[CH:14][CH:13]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 108668795-Fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chlorideHCID 21899848Ethylacetate heptaneHCID 43591686N-[2-(biphenyl-4-yloxy)ethyl]cyclopropanamine

Produkt 1

HCID 67071809N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamideAusbeute 47,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

At ambient temperature, a solution of 230 mg (1.29 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a mixture of 300 mg (1.18 mmol) of N-[2-(biphenyl-4-yloxy)ethyl]cyclopropanamine as its hydrochloride salt and 250 mg (2.48 mmol) of triethylamine in 5 ml of tetrahydrofurane. The reaction mixture is stirred for 2 hrs at 80° C. The solvent is removed under vacuum and 10 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×25 ml) and the combined organic layers are successively washed by a 1 N solution of HCl, a saturated solution of potassium carbonate and brine and dried of magnesium sulfate to gave after concentration 750 mg of a yellow oil. Column chromatography (gradient heptane/ethyl acetate) yielded 220 mg (47% yield) of N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide as a colourless oil (M+H=394).

Aufarbeitung

  1. customThe solvent is removed under vacuum and 10 ml of water
  2. additionare then added to the residue
  3. extractionThe watery layer is extracted twice with ethyl acetate (2×25 ml)
  4. washthe combined organic layers are successively washed by a 1 N solution of HCl
  5. dry with materiala saturated solution of potassium carbonate and brine and dried of magnesium sulfate
  6. customto gave after concentration 750 mg of a yellow oil

Quellen und Nachweise

ORD-Eintrag
ord-a75bfc9af4ef48eba05ebfdd706ba5e9
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841332B2

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